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LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
TODAYrsquoS SCIENCE TARGETING TUMOR
DNA FUNCTIONS
TOMORROWrsquoS NEW HOPE AGAINST RESISTANT CANCER
September 2020
IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions
This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and is notto be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subject toindependent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable to companieslisted on Euronext Paris including in particular the risk factors described in in the most recent Companyrsquos Universal Registration Document filed with the French Financial Markets Authority (Autoriteacute des marcheacutesfinanciers) in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)
This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based on theknowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have not beenverified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitive position datacontained in the Information
The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution or usewould be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer or thesolicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectusthat complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the UnitedKingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the US Securities Act of1933 as amended or an exemption from registration thereunder
This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements contained inthis document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or to confirmprojections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document
Important Information
September 2020
Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
3
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q1 2022 supports strategic plan to deliver key near-term clinical milestones
STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with strong translational amp clinical expertise led by experienced management and board of directors with demonstrated track record in product amp business development
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of oligonucleotides generating new compounds
AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist with a unique ability to abrogate resistance to targeted therapies
OX401 a newly optimized PARP agonist with potent activity on tumor control and immune response
A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates from preclinical stage to proof-of concept in man the best inflection points to monetize these assets and generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
September 2020
FRANCOISE BONO (PHD)
CSO(Sanofi Evotec)
Formerly Executive Vice-President Oncology of Evotec
Experienced management team with demonstrated track record in product amp business development
4
JUDITH GRECIET (PHARMD)
CEO
OLIVIER DE BEAUMONT (MD)
CMO(Aventis Quintiles Stallergenes Greer)
Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs of Stallergenes Greer
PHILIPPE MAITREEVP of Onxeo US CBDO
(Aventis PPD Oscient mAbRx)
Formerly Chief Executive Officer and Co-Founder of mAbRx
NICOLAS FELLMANN
CFO(Ernst amp Young Pfizer)
Formerly Director of Treasury Tax amp Audit of Pfizer France
(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France
September 2020
platONtrade-derived compounds share a decoy-agonist mechanism of action providing a radically disruptive approach to cancer treatment
5
All candidates based on this mechanism of action hijack (decoy effect) and hyper-activate (agonist effect) their therapeutic targets leading to ineffective DNA functions without inducing any resistance
2 compounds already derived from platONtrade each very differentiated in terms of target and activity
AsiDNAtrade first-in-class front runner DNA repair inhibitor acting upstream of the DDR cascade with a unique ability to abrogate acquired resistance to targeted therapies
OX401 next-generation compound targeting PARP and activating the immune response via the STING pathway
Active component
Double-stranded ADN fragment (oligonucleotide) Variable sequence and length to optimize target binding amp activation
LinkerTethered loop
to prevent dissociation
VectorWhen appropriate
to facilitate tumoral ampnuclear uptake
platONtrade a versatile library of decoy-agonist oligonucleotides generating disruptive drug candidates
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions
This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and is notto be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subject toindependent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable to companieslisted on Euronext Paris including in particular the risk factors described in in the most recent Companyrsquos Universal Registration Document filed with the French Financial Markets Authority (Autoriteacute des marcheacutesfinanciers) in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)
This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based on theknowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have not beenverified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitive position datacontained in the Information
The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution or usewould be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer or thesolicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectusthat complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the UnitedKingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the US Securities Act of1933 as amended or an exemption from registration thereunder
This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements contained inthis document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or to confirmprojections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document
Important Information
September 2020
Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
3
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q1 2022 supports strategic plan to deliver key near-term clinical milestones
STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with strong translational amp clinical expertise led by experienced management and board of directors with demonstrated track record in product amp business development
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of oligonucleotides generating new compounds
AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist with a unique ability to abrogate resistance to targeted therapies
OX401 a newly optimized PARP agonist with potent activity on tumor control and immune response
A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates from preclinical stage to proof-of concept in man the best inflection points to monetize these assets and generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
September 2020
FRANCOISE BONO (PHD)
CSO(Sanofi Evotec)
Formerly Executive Vice-President Oncology of Evotec
Experienced management team with demonstrated track record in product amp business development
4
JUDITH GRECIET (PHARMD)
CEO
OLIVIER DE BEAUMONT (MD)
CMO(Aventis Quintiles Stallergenes Greer)
Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs of Stallergenes Greer
PHILIPPE MAITREEVP of Onxeo US CBDO
(Aventis PPD Oscient mAbRx)
Formerly Chief Executive Officer and Co-Founder of mAbRx
NICOLAS FELLMANN
CFO(Ernst amp Young Pfizer)
Formerly Director of Treasury Tax amp Audit of Pfizer France
(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France
September 2020
platONtrade-derived compounds share a decoy-agonist mechanism of action providing a radically disruptive approach to cancer treatment
5
All candidates based on this mechanism of action hijack (decoy effect) and hyper-activate (agonist effect) their therapeutic targets leading to ineffective DNA functions without inducing any resistance
2 compounds already derived from platONtrade each very differentiated in terms of target and activity
AsiDNAtrade first-in-class front runner DNA repair inhibitor acting upstream of the DDR cascade with a unique ability to abrogate acquired resistance to targeted therapies
OX401 next-generation compound targeting PARP and activating the immune response via the STING pathway
Active component
Double-stranded ADN fragment (oligonucleotide) Variable sequence and length to optimize target binding amp activation
LinkerTethered loop
to prevent dissociation
VectorWhen appropriate
to facilitate tumoral ampnuclear uptake
platONtrade a versatile library of decoy-agonist oligonucleotides generating disruptive drug candidates
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
3
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q1 2022 supports strategic plan to deliver key near-term clinical milestones
STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with strong translational amp clinical expertise led by experienced management and board of directors with demonstrated track record in product amp business development
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of oligonucleotides generating new compounds
AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist with a unique ability to abrogate resistance to targeted therapies
OX401 a newly optimized PARP agonist with potent activity on tumor control and immune response
A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates from preclinical stage to proof-of concept in man the best inflection points to monetize these assets and generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
September 2020
FRANCOISE BONO (PHD)
CSO(Sanofi Evotec)
Formerly Executive Vice-President Oncology of Evotec
Experienced management team with demonstrated track record in product amp business development
4
JUDITH GRECIET (PHARMD)
CEO
OLIVIER DE BEAUMONT (MD)
CMO(Aventis Quintiles Stallergenes Greer)
Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs of Stallergenes Greer
PHILIPPE MAITREEVP of Onxeo US CBDO
(Aventis PPD Oscient mAbRx)
Formerly Chief Executive Officer and Co-Founder of mAbRx
NICOLAS FELLMANN
CFO(Ernst amp Young Pfizer)
Formerly Director of Treasury Tax amp Audit of Pfizer France
(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France
September 2020
platONtrade-derived compounds share a decoy-agonist mechanism of action providing a radically disruptive approach to cancer treatment
5
All candidates based on this mechanism of action hijack (decoy effect) and hyper-activate (agonist effect) their therapeutic targets leading to ineffective DNA functions without inducing any resistance
2 compounds already derived from platONtrade each very differentiated in terms of target and activity
AsiDNAtrade first-in-class front runner DNA repair inhibitor acting upstream of the DDR cascade with a unique ability to abrogate acquired resistance to targeted therapies
OX401 next-generation compound targeting PARP and activating the immune response via the STING pathway
Active component
Double-stranded ADN fragment (oligonucleotide) Variable sequence and length to optimize target binding amp activation
LinkerTethered loop
to prevent dissociation
VectorWhen appropriate
to facilitate tumoral ampnuclear uptake
platONtrade a versatile library of decoy-agonist oligonucleotides generating disruptive drug candidates
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
FRANCOISE BONO (PHD)
CSO(Sanofi Evotec)
Formerly Executive Vice-President Oncology of Evotec
Experienced management team with demonstrated track record in product amp business development
4
JUDITH GRECIET (PHARMD)
CEO
OLIVIER DE BEAUMONT (MD)
CMO(Aventis Quintiles Stallergenes Greer)
Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs of Stallergenes Greer
PHILIPPE MAITREEVP of Onxeo US CBDO
(Aventis PPD Oscient mAbRx)
Formerly Chief Executive Officer and Co-Founder of mAbRx
NICOLAS FELLMANN
CFO(Ernst amp Young Pfizer)
Formerly Director of Treasury Tax amp Audit of Pfizer France
(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France
September 2020
platONtrade-derived compounds share a decoy-agonist mechanism of action providing a radically disruptive approach to cancer treatment
5
All candidates based on this mechanism of action hijack (decoy effect) and hyper-activate (agonist effect) their therapeutic targets leading to ineffective DNA functions without inducing any resistance
2 compounds already derived from platONtrade each very differentiated in terms of target and activity
AsiDNAtrade first-in-class front runner DNA repair inhibitor acting upstream of the DDR cascade with a unique ability to abrogate acquired resistance to targeted therapies
OX401 next-generation compound targeting PARP and activating the immune response via the STING pathway
Active component
Double-stranded ADN fragment (oligonucleotide) Variable sequence and length to optimize target binding amp activation
LinkerTethered loop
to prevent dissociation
VectorWhen appropriate
to facilitate tumoral ampnuclear uptake
platONtrade a versatile library of decoy-agonist oligonucleotides generating disruptive drug candidates
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
platONtrade-derived compounds share a decoy-agonist mechanism of action providing a radically disruptive approach to cancer treatment
5
All candidates based on this mechanism of action hijack (decoy effect) and hyper-activate (agonist effect) their therapeutic targets leading to ineffective DNA functions without inducing any resistance
2 compounds already derived from platONtrade each very differentiated in terms of target and activity
AsiDNAtrade first-in-class front runner DNA repair inhibitor acting upstream of the DDR cascade with a unique ability to abrogate acquired resistance to targeted therapies
OX401 next-generation compound targeting PARP and activating the immune response via the STING pathway
Active component
Double-stranded ADN fragment (oligonucleotide) Variable sequence and length to optimize target binding amp activation
LinkerTethered loop
to prevent dissociation
VectorWhen appropriate
to facilitate tumoral ampnuclear uptake
platONtrade a versatile library of decoy-agonist oligonucleotides generating disruptive drug candidates
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Current cutting-edge RampD pipeline with unique mechanisms of action in DDR
6
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401PARP agonist + STING pathway activation
OX401 + immunotherapy
AsiDNAtradeSafety Activity
AsiDNAtrade + chemotherapySafety in combo Synergistic efficacy
AsiDNAtrade + PARPi Resistance abrogation
AsiDNAtrade + other targeted txResistance abrogation prevention
DRIIV -1b
DRIIV
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONSD
NA
Dam
age
R
esp
on
se
In vivo proof of concept
In-vivo proof-of efficacy
DD
R
+ IO
REVOCAN
Completed or ongoing Legend Planned short-term
In-vivo proof-of concept
PARP inhibitors (PARPi) are a leading class of targeted therapies the first approved and marketed in the field of DDR
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
AsiDNAtrade
Unique Decoy-Agonist Mechanismof Action in DNA Damage Response
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
AsiDNAtrade a first in class product in the clinically-validated field of DDR
8Source Quanz M et al Clin Cancer Res 2009 151308-1316 Quanz M et al PLoS ONE 2009 4(7) - Jdey W et al Clin Can Res 201622
Decoy-agonist mode of action avoids compensatory mechanisms blocking the induction of resistance
AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of the genetic context
Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile
AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip
hellip diverts them away from the true damage hellip hellip leading to cellular death
5rsquo 3rsquo
3rsquo 5rsquo
Double-stranded 32 bp DNA is tethered with a loop to prevent dissociation2
Cholesterol
Loop
Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1
Binding and activating DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Sequence non-homologous and not immunogenic (CpG-free)
Patent Protection (CoM AsiDNAtrade amp
related compounds) until 2031
Extendable to 2036(SPC amp PTE)
Combination patents up to 2040
IP
Active 32 bp DNA duplex
A unique ldquodecoy agonistrdquo mechanism of actionA purpose-designed oligonucleotide
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
An extensive preclinical program paves the way to ambitious clinical translation
9
Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)
Autosensitization and noresistance observed In multiple cell lines Confirmed
Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines
No restriction to specific genetic context
AsiDNAtrade increases survival amp responders to PARPi
Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival
Abrogation of resistance to PARPi In multiple cell lines AsiDNAtrade stops resistance to PARPi
Abrogation prevention of resistance to other targeted tx
Ongoing validation with several TKI KRASi hellipPrelim data confirmed prolongation of anti-EGFR anti-ALK efficacy
In vitro data In vivo data
PARP inhibitors (PARPi) and tyrosine kinase inhibitors (TKI) are leading approved targeted therapies in oncology
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Potential indications Market size1 (incidence 2020)
Neoadjuvant treatment for locally advanced triple negative breast cancer
1L 2L (platinum-sensitive) treatment of advanced ovarian cancer
1L advanced Non-small cell lung cancer treated with platinum
TNBC localregional disease 116 000 pts
Advanced OC 42 000 pts ()
Advanced NSCLC wo mutations 179 000 pts
1L2L treatment of gBRCAm HER2- metastatic breast cancer (w ola andor Talazo)
2L treatment of metastatic castration-resistant prostate cancer HRR gene mutated (w olaparib)
Advanced HER2- BC 119 000 pts
gBRCAm = 11 000 pts
mCRPC 98 000 pts
gBRCAm = 13 000 pts
1L 2L maintenance of advanced ovarian cancer (w ola nira rucaparib)
1L maintenance of gBRCAm metastatic pancreatic cancer (w olaparib)
Advanced OC 42 000 pts
mPaC 119 000 pts ()
gBRCAm = 6 000 pts
1L treatment of EGFR+ Non small cell lung cancer (w anti-EGFR TKI andor other TT)
Advanced NSCLC EGFR+ 111 000 pts
AsiDNAtrade full clinical potential overview
Combo with carboplatin bull Improve response dur of responsebull Preserve sensitivity to platinum
Combo with PARPibull Improve response dur of responsebull Enlarge addressable population
(BRCAwt)
Combo with PARPibullDelay time to progression under
PARPi (maintenance)
Combo with targeted therapiesbullDelay time to progression
Sy
NE
RG
Y
RE
SI
TA
S
NCE
1 source GlobalData for 8MM countries (US 5EU JPN CHN) except () without CHN 10
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Current clinical program delivering the promises of AsiDNAtrade to patients
11
Safety Validation Proof-of-Mechanism in man
DRIIV-1 Phase 1
First IV administration in solid tumors
Favorable safety via IV
Proof of mechanism in tumors
Safety Validation in Combo Efficacy with Chemotherapies
DRIIV-1b Phase 1b (IV)
Combo with carboplatin +- paclitaxel
Excellent safety in combination with carboplatin
Ongoing Safety in combination with carbo + pacli
Ongoing Preliminary signals of efficacy
Abrogation of Acquired Resistance to Targeted Therapies
REVOCAN Phase 1b2 (IV)Relapsed ovarian cancer in addition to PARPi niraparib
Ongoing Abrogation of resistance to PARPi
FPI expected Q3 2020
Under explorationPhase 1b2 (IV) Non small cell lung cancer in addition to other targeted tx (TKIs hellip)
Abrogation of resistance to targeted therapies
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
DRIIV Phase 1 Favorable safety profile amp demonstrated proof-of-mechanism
12
Phase 1 study via IV route
Open-label 3+3 dose escalation from 200mg to 1800mg
22 patients 5 doses
Study coordinator Pr C Le Tourneau (Institut Curie)
Objectives to determine the safety and PKPD profile of AsiDNAtrade
Primary objective reached favorable safety outcome
AsiDNAtrade 200mg 400mg 600mg No drug-related serious adverse event (SAE) and no dose-limiting toxicity (DLT)
AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose
MTD was not reached
181 (89)
22 (11)1
Grade 12
Grade 3
Grade 4
Non-related95
Non-related77
Adverse Events
Proof-of-mechanism Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement
Activity pharmacodynamic biomarkers (on tumor biopsies)
Pre-treatment Post-treatment
γH2AX Readout of DNA-PK target engagement
Patient 003-001
Access poster presented at EORTC-AACR 2019
Access publication A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals
13
AsiDNAtrade 600 mgCohort 13 pts
carboplatin
AsiDNAtrade 600 mg carboplatin + paclitaxelCohort 26 pts
+Heavily treated patients with advanced solid tumors progressing at inclusion
No DLT and very good tolerance of the combination
Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)
Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines
Timelines include Covid-19 impact to date and may be further reviewed
Ongoing 3 patients treated
DSMB approved the next 3-patient step after reviewing the safety profile of the combination
Topline results expected end 2020
+
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Acquired resistance to PARP inhibitors evolves from drug-tolerant cells (DTC) vulnerable to AsiDNAtrade
14
Onxeo showed that resistance to PARPi evolves from DTC1
AsiDNAtrade is dramatically more efficient on DTC than on parental cells
Olaparib AsiDNAtrade
TNBC model BC227 BRCA2 --
Parental cell primary tumor cell - TKI tyrosine kinase inhibitors1 AACR 2020 - Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade2 Sharma VS et al Cell 2010 141-1 69-80
AsiDNAtrade prevents resistance to PARP inhibitors by acting on DTC1
Drug pressure
Drug-tolerant cells (dormantquiescent
tolerantpersisterhellip cells)
Reactivation(tumor recurrence)
Tumor microenvironment(TME)
TME
DTC are already an established cause2 of resistance to TKI
AsiDNAtrade could effectively counter DTC-driven acquired resistance to a wide range of targeted therapies
IC50 olaparib ndash parental cells 5M IC50 AsiDNAtrade ndash DTC 17nMM
olaparib AsiDNAtrade
No activity on DTC
DTCeradication
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
REVOCAN Phase 1b2 A key ongoing study to assess the effect of AsiDNAtrade on resistance to PARPi niraparib in ovarian cancer
15
Clinical research agreement with Gustave Roussy PI Dr P Pautier supported by Arcagy Gineco Network
n= up to 26 patients platinum-sensitive relapsed ovarian cancer under 2nd line of maintenance with niraparib gt 6 months
Inclusion at CA 125 increase (established predictive biomarker of resistance in OC)
Primary objective Safety run amp CA125 decrease (GCIG criteria)
Secondary objective Efficacy - PFS (RECIST criteria) - OS
REVOCANREVersion of resistance in Ovarian Cancer
with AsiDNAtrade and Niraparib
Approved by the regulatory authorities in late May 2020
FPI from Q3 2020 preliminary data in early 2021
Timelines include Covid-19 impact to date and may be further reviewed
UW
B1
28
9 (
Ova
rian
can
cer
mo
de
l ndashB
RC
A1
-- )
Days post-treatment
AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)
AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
AsiDNAtrade First-in-class therapy designed to address a major challenge in oncology resistance to treatment
16
Decoy Agonist MoA does not induce resistance
Differentiated Decoy Agonist MoAin the clinically-validated field of DNA Damage Response
Long IP (up to 2040)
Clinical-stage assetFavorable safety profile incl in combination Proof of mechanism signals of efficacy
Collaborations with top-academic centers(Institut Curie - Gustave Roussy ndash Oncopole Toulousehellip)
REVOCAN Phase 1b2 to evaluate the addition of AsiDNAtrade on the abrogation of acquired resistance
to niraparib (to start Q3 2020)
Depletes the drug-tolerant cells from which resistance to targeted therapies emerge
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
OX401
Next-generation compound targeting PARPwith strong immune response activation
17
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
OX401 is a PARP agonist that triggers the immune response
18
The 2nd purpose-designed oligonucleotide from platONtrade
Active 16 bp DNA duplex
Double-stranded 16 bp DNA tethered with a loop to prevent dissociation
Genomic DNA length optimized to specifically bind and activate PARP enzymes
Optimized to be non-homologous and non- immunogenic (CpG-free)
Modified to enhance intracellular stability
Patent Protection until 2038
(Composition of Matter of OX401 amp
related compounds)
Extendable to 2043 with SPC amp PTE
IP
Potent PARP activation after OX401 treatment
Untreated OX401
OX401 binds PARP (decoy) and then hyperactivates the protein (agonist) diverting it away from its role in tumor DNA Damage Response and leading to a significant immune response
PARP Inhibitors and DDR Summit 2020 Introducing OX401 a Next Generation PARP Inhibitor Able to Exploit Metabolic Vulnerabilities of Cancer Cells and Inducing a Potent STING Response
PARylation (fluorescence microscopy)
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
OX401 benefits from platONtradersquos key features while displaying an original and promising efficacy profile
19
Based on a decoy agonist mechanism OX401 shows same favorable tolerance profile as AsiDNAtrade and no resistance
OX401 is more effective on tumor control than a reference PARP inhibitor olaparib
Syngenic mouse breast cancer model - EMT6 (PARP)
Robust adaptive and innate immune response through the activation of the STING pathway
Lymphoma - U937 cell line
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
Outlook
20
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Short-term key clinical catalysts in 2020 2021
21
DRIIV-1b cohort 2
Topline data
H1 2020 H2 2020
REVOCAN First data set
(1b part)
DRIIV-1b Enrolment resumed
(post Covid-19)
In vivo validation to support clinical
translation
In-vivo validation of
OX401 profile
Tolerance in combination + first signals of efficacyDRIIV-1bAsiDNAtrade +
carboplatin +-paclitaxel
REVOCANphase 1b2
AsiDNAtrade + niraparib
Reversion of Resistance
Abrogation of resistanceAsiDNAtrade + TKI or other targeted tx
Preclinical proof-of-concept
PARP agonist + activation of immune responseOX401
Preclinical proof of efficacy
Timelines include Covid-19 impact to date and may be further reviewed
Reg approvals
FPI
In-vivo validation of combo w CPI
H2 2021
DRIIV-1b Final data
REVOCAN Top line data
H1 2021
Reg tox study and full translational profile
Ready for FIM
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Financial resources in line with key development milestones objectives
22
Financiegravere de la Montagne
13
Invus11
Free float76
Cash position of euro73m at 03312020 - HY 2020 results on September 17 2020
+ euro6m from transaction with Acrotech on 04062020
+ euro73m from private placement on 06092020 to Invus new long-term
shareholder amp Financiegravere de la Montagne historical shareholder
Cash runway to Q1 2022
Shares outstanding 783m
Average Daily Volume 453358 shares
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
At 08312020YTD at 08312020
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
Onxeo in 20202021 Ready for success
23
Deep expertise in oligonucleotides and platONtrade leading to optimized development plan
Financial visibility to Q1 2022 well beyond key clinical catalysts for the Company
AsiDNAtrade first-in-class DDR inhibitor addressing a major oncology challenge resistance to targeted therapies
Confirmed activity and favorable safety profile in man (DRIIV)
REVOCAN phase 1b2 major catalyst to demonstrate that AsiDNAtrade added to niraparib reverses tumor resistance in ovarian cancer First study outcomes expected in the short term (end 2020early 2021)
platONtrade platform generates promising compounds based on unique decoy agonist mechanism of action
Each candidate is designed to target specific proteins involved in different DNA functions
OX401 preclinical in vivo profile confirmed potent antitumoral activity and strong activation of the immune response
Full preclinical package and clinical readiness expected mid 2021
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
Publications
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
AsiDNAtrade Selected Publications (12)
25
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 June24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
September 2020
AsiDNAtrade Selected Publications (22)
26
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 June 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097
A Phase 1 dose-escalation study to evaluate safety pharmacokinetics and pharmacodynamics of AsiDNA a first-in-class DNA repair inhibitor administered intravenously in patients with advanced solid tumours Le Tourneau et al British Journal of Cancer 25 August 2020 httpsdoiorg101038s41416-020-01028-8
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatmentMolecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes
EORTC-NCI-AACR 2019
Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors
AACR 2020 Virtual Meeting
Acquired resistance to PARP inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNAtrade
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO
Olivier de Beaumont ndash CMO
Tel +33 1 45 58 76 00COMPANY INFORMATION
wwwonxeocominvestorsonxeocom