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Company presentationMay 11, 2018
1
Significant progress in 2017
› Continued progress in several clinical studies
› Publication of clinical results inThe New England Journal of Medicine
› Increase in Swedish, British and US institutional shareholding
› 65 MUSD raised to finalize clinical trials and prepare for filing
› Increased attention from EMA through access to PRIME
2
Forward-looking statements
This presentation may contain certain forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on Hansa Medical’s business, financial condition and results of operations. The terms “anticipates”, “assumes”, “believes”, “can”, “could”, “estimates”, “expects”, “forecasts”, “intends”, “may”, “might”, “plans”, “should”, “projects”, “will”, “would” or, in each case, their negative, or other variations or comparable terminology are used to identify forward-looking statement. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied in a forward-looking statement or affect the extent to which a particular projection is realized. Factors that could cause these differences include, but are not limited to, implementation of Hansa Medical’s strategy and its ability to further grow, risks associated with the development and/or approval of Hansa Medical’s products candidates, ongoing clinical trials and expected trial results, the ability to commercialize IdeS, technology changes and new products in Hansa Medical’s potential market and industry, the ability to develop new products and enhance existing products, the impact of competition, changes in general economy and industry conditions and legislative, regulatory and political factors.
No assurance can be given that such expectations will prove to have been correct. Hansa Medical disclaims any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
3
Company facts
› Biopharma company founded 2007
› Listed on Nasdaq Stockholm (ticker: HMED) · Market cap: SEK 9.9 B / USD 1.1 B (May 9, 2018)· Cash position: SEK 575 M / USD 68 M (March 31, 2018)· Net loss Q1 2018: SEK -46 M / USD -5.4 M
› Approx. 40 employees in Lund, Sweden and the US
› Significant collaborations:· Cedars-Sinai Medical Center, Los Angeles· NYU Langone Medical Center, New York· Johns Hopkins Medicine, Baltimore· Necker Hospital, Paris· Uppsala University Hospital· Lund University
4
Breakthrough therapy for rapid inactivation of IgG antibodies5
Clinical proof-of-concept demonstrated in several clinical studies – Recent publication in The New England Journal of Medicine (Aug 2017)
Treatment of transplant rejection and acute autoimmune diseases
IgG modulating enzymes – A novel mode-of-action
IdeS
6
IgG Fc
F(ab’)2
IdeS
IdeS: A unique, novel mechanism› IgG-degrading enzyme of
Streptococcus pyogenes
› Effectively cleaves IgG
› A novel approach to rapidly eliminate pathogenic IgG
7
IdeS effectively and rapidly degrades IgG› Very effective inactivation of IgG1
› Rapid onset
› An antibody-free window for approximately a week
Note: 1) Winstedt el al. (2015) PLOS ONE 10(7)
8
00.
5 h
1 h
2 h
4 h
6 h
8 h
1 d
2 d
3 d
7 d
14 d
21 d
28 d
64 d
0
2
4
6
8
10
[IgG
] (m
g/m
L)
IgG in human serum
n=10 patients
ADA toBiologics
ADA toGene Therapy
Anti-Drug Antibodies
MGrelapse
MSrelapse
AcuteITP Myasthenic
crisis
Dilatedcardiom.
Pemph.relapse
CIDP
Graves disease
NMOrelapse
NMDARE
LEMS
CAPS
ANCA (GPA)
SLEflares
Lupusnephritis
Anti-GBM
GBS
IgG-related autoimmune diseases
EnzE
BoneMarrow Oncology
ABOi
KidneyHLA
LiverHLA
LungHLA
HeartHLA
Transplantation
Pre-transplant treatment
KidneyAMR
LungAMR
HeartAMR
LiverAMR
Acute AMR
Planned studies Ongoing studies Number of patients
IdeS potential indication universe9
The addressable patient population for prioritized indications is ~36 000 in the seven major markets (7MM*)
1) Organ Procurement and Transplantation Network (OPTN); EDQM Council of Europe2) Jordan et al. British Medical Bulletin, 2015, 114:113-125 3) http://www.irodat.org4) Internal report5) Kluth et al. J Am Soc Nephrol. 1999 Nov;10(11):2446-536) Bloodcell transplant HRSA 2014, Center for International Blood and Marrow Transplant Research® (CIBMTR) as of January 20, 2016, Gratwohl-2010, Passweg-2016, Zachary-20147) Chih et al. The Journal of Heart and Lung Transplantation, Vol 35, No 8, August 20168) McGrogan et al. Neuroepidemiology 2009;32(2):150-63
* US, Germany, UK, France, Spain, Italy, and Japan
10
0
10 000
20 000
30 000
40 000
Kidney transplant,AMR and ABOi
(1, 2, 3, 4)
Heart and lungtransplant (5)
Bone marrowtransplant (6)
Anti-GBM (7) GBS (8) Total
# of patients
Transplantation market outlook
11
HLA Sensitized PatientsMeaning
› anti-HLA antibodies to potential donors
› anti-HLA antibodies due to pregnancy, earlier transplant or blood transfusion
Prevalence
› 30% of patients on transplant waitlists are sensitized1,2
Note: 1) Jordan et al. British Medical Bulletin, 2015, 114:113-1252) Orandi et al. NEJM, 2016;374:940-50
12
PRA levels on kidney transplant wait-list
9%
15%
6%
70%
20<80%0-20% 80<98% 98-100%
500,
000
400,
000
300,
000
200,
000
100,
000
0
Cos
t in
USD
The importance of desensitization
Note: 1) Orandi et al, NEJM,, 374;10, March 10, 2016. 2) www.usrds.org. 3) Shehata et al., Transfus Med Rev. 2010;24 Suppl 1: S7–S27
$178,254
$423,195
Kidney transplantation2,3
5 years of immunosuppression3
5 ye
ars
of d
ialys
is3
Increased survival rate1 Lowered cost
77%
44%
0%
20%
40%
60%
80%
100%
Dialysis Transplantation
8-year survival ratefor sensitized patients
› Long-term dialysis results in cardiovascular complications
Avoiding complications!
13
IdeSOverview of finalized and ongoing clinical studies in transplantation
14
IdeS Development in Transplantation is Going According to Plan
Jordan et al. The New England Journal of Medicine 2017;377:442-53 “IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation”
15
Study Subjects StatusPatients incl. in The New England Journal of Medicine (2017)
Phase I (SWE) 29 healthy subjects • Completed 2014
Phase II (SWE) 8 sensitized patients • Completed 2015 1 patient
Phase II (SWE) 10 sensitized patients • Completed 2016 10 patients
Phase II (US) 17 highly sensitized patients • Fully enrolled. Finalization
by end of Q3 2018 14 patients
Multicenter Phase II
18 highly sensitized patients • Fully enrolled. Finalization
by end of Q3 2018
Data published in The New England Journal of Medicine1
demonstrate potential of IdeS
› All HLA-antibodies eliminated
› 24/25 patients had normalized kidney function six months post transplantation
› One graft loss occurred (non-HLA IgM & IgA)
› Five biopsy confirmed episodes of antibody-mediated rejection (AMR)
› All AMRs responded well to treatment
› IdeS is generally well tolerated and effective
1. Jordan et al. The New England Journal of Medicine 2017;377:442-53 “IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation”
16
Normalized kidney function 6 months post transplant in the 24 patients
17
1
Months after transplantation
Cre
atin
ine
(mg/
dL)
Tx0
5
10
15
2 3 4 5 6
Latest clinical update – January 201818
› Completed enrollment in multi-center IdeS Phase II study Highdes
› Completed enrollment in US Phase II study with IdeS
› In total 35 patients treated and transplanted
› IdeS enabled kidney transplantation for all 35 patients
› 6 month follow up data end of Q3 2018
Aiming at BLA/MAA filing late 2018 19
Potential approvals
20192018
Finalize recruitment
2020
Potential launch of IdeS for kidney Tx
Filing BLA/MAA
6 month follow-up
IdeS beyond desensitization Ongoing and planned Phase II studies in additional indications
20
Additional Phase II studies ongoing and planned21
Indication Description Number of patients Status
Anti-GBM disease
Ultra rare kidney disease. Approx. 15
Ongoing. 7/15 patients treated as of March 31, 2018
AMRAntibody mediated rejection post transplantation
Approx. 15-25 Anticipated start H2 2018
Guillain-Barrésyndrome
IgG attack on peripheral nerves Approx. 30 Anticipated start H2
2018
Current focus: Prioritized indications
1st
Ph. II
HighdesGBS
2nd
Ph. II3rd
Ph. II AMR
Anti-GBM
ABOi
EnzE
Lung
Heart
Planned studies
TransplantationAcute IgG-related
autoimmune diseases Cancer
Relapsing IgG-related autoimmune diseases
(Next generation)
NiceRIdeS
BMT
Development strategy for IdeS and novel IgG cleaving enzymes for repeat dosing (NiceR)
22
Near term focus
› Finalization of Highdes end of Q3 2018 with six month data
› Finalization of US Phase II end of Q3 2018 with six month data
› End-of Phase II meetings with FDA and EMA
› Potential IdeS BLA/MAA filing in transplantation in late 2018or early 2019
› Initiate Phase II in Antibody Mediated Rejection (AMR) and Guillain-Barré syndrome (GBS)
23
Q&A
24
Appendix
25
Financials, shareholders and corporate governance
26
27
SEK m (unless otherwise stated)Q1 Q1 Year Year
2018 2017 2017 2016
Net revenue 0.6 1.1 3.4 2.6
Sales, general and administration expenses -15.5 -9.8 -43.7 -29.7
of which cost, LTIP 2016 -4.9 -0.3 -4.5 -0.1
Research and development expenses -31.5 -36.2 -137.1 -82.9
of which cost LTIP 2016 -0.4 -1.0 -5.4 -0.4
Operating profit/loss -46.6 -44.8 -176.1 -111.1
Cash flow from operating activities -44.1 -43.7 -150.1 -94.6
Cash and cash equivalent* 575.0 209.4 616.1 253.6
FTE’s end of period 35 30 33 27
of which R&D 28 25 27 23
First quarter 2018 financials
* including short term investments
27
The SG&A expenses reflect the continued build-up of the organization to prepare for commercial launch.
R&D expenses in Q1 2017 included significant investment in IdeSmanufacturing process.
28
NameNumber of
sharesShare
(%)
Nexttobe AB 9,443,761 24.9Thomas Olausson (private and via company) 1,548,569 4.1Oppenheimer 1,415,560 3.7Handelsbanken Fonder 1,333,566 3.5Avanza Pension 1,314,043 3.5Gladiator 915,000 2.4AFA Försäkring 841,639 2.2Norron Fonder 778,201 2.1Polar Capital 610,190 1.6BWG Invest Sàrl 600,370 1.6Tredje AP-fonden 561,465 1.5Catella Fonder 513,639 1.4Sven Sandberg 512,000 1.4C WorldWide Asset Management 457,291 1.2Invesco 416,536 1.1Other 16,616,295 43.8In total 37,878,125 100.0
Source: Monitor by Modular Finance AB. Compiled and processed data from various sources, including Euroclear, Morningstar and the Swedish Financial Supervisory Authority (Finansinspektionen).
28
15 largest shareholders
March 31, 2018
Directed share issue resolved on November 29, 2017
› USD 65 million / 2.8 million shares
› Accelerated book building process by RBC, Evercore and SEB to international and Swedish reputable long-only investors and international sector specialists
› Provides funding for 2018 and 2019
› Proceeds enables:· Finalization of clinical studies in highly sensitized patients· Prepare market approval in the US and EU· Up to four additional Phase II in transplantation and acute autoimmunity· Development of next generation of IgG eliminating enzymes· Further Investigations of Hansa Medical technology in oncology
29
Management Team30
Soren Tulstrup, President and CEO (2018)Former CEO of Vifor Pharma AG and Santaris Pharma A/S. Soren has also served as Senior Vice President, Global Franchise Head, MPS at Shire Pharmaceuticals in several senior commercial roles within Merck & Co., Inc. and Sandoz Pharma AG (Novartis). He holds a Master of Science, Economics and Business Administration from Copenhagen Business School.
Dr. Christian Kjellman, Senior Vice President Research and DevelopmentJoined Hansa Medical in 2008 after serving at BioInvent AB and Cartela AB. Assistant Professor in Molecular Genetics at Lund University. Christian holds an M.Sc. in Chemical Biology and a Ph.D. in Tumour Immunology from Lund University.
Henk Doude van Troostwijk, Vice President, Commercial OperationsHenk joined Hansa Medical in May 2016. He has extensive management experience in sales and marketing in the areas of transplantation and orphan drugs. from Raptor Pharmaceuticals and Genzyme Europe BV. Henk holds an MBA from Henley Management College, UK.
Karin Aschan, Vice President, Regulatory AffairsKarin joined Hansa in 2016. She has a long experience from working within Regulatory Affairs, initially at AstraZeneca and later as Head of Regulatory Affairs at Active Biotech and at ClinicalDataCare. Karin holds a M.Sc. in Pharmacy from Uppsala University.
Management Team (continued)
31
Eva-Maria Joed, Vice President, Chief Financial OfficerEva-Maria joined Hansa Medical in 2015. She has held positions both as Chief Accountant and CFO at Kemira Kemi AB, Johns Manville AB within the Berkshire Hathaway group and Procordia Food AB Eva-Maria holds an M. Sc. in Business and Economics from Lund University.
Emanuel Björne, Vice President, Business Development and Investor RelationsJoined Hansa Medical in 2007 - experience as start-up CEO at Hansa Medical, research analyst at Biolin Scientific and analytical chemist at Polypeptide Labs. Emanuel holds an M.Sc. in Engineering Physics (biophysics core) from Lund University and the University of California at Santa Barbara.
Dr. Lena Winstedt, Vice President, Project ManagementBefore joining Hansa Medical in 2011, she served at BioInvent International AB, Genmab A/S and H. Lundbeck AB. Lena holds an M.Sc. in Molecular Biology from Lund University and the University of Glasgow and a Ph.D. in Microbiology from Lund University.
Max Sakajja, Vice President, Corporate StrategyMax joined Hansa Medical in 2017. He has broad corporate development background and experience within corporate finance, strategy and business development from Biovitrum, Sobi and Envirotainer. Max holds an M.Sc. in Biotechnology from the Royal Institute of Technology.
Board of Directors32
Ulf Wiinberg, Chairman of the board (2016)Former CEO of H Lundbeck A/S. Also served as president of global consumer health care business and European pharma business at Wyeth.
Dr. Angelica Loskog (2016)Professor at the Department of Immunology, Genetics and Pathology at Uppsala University. Scientific advisor to Nexttobe AB.
Hans Schikan (2015)Sobi (Swedish Orphan Biovitrum, publ), InteRNA, Dutch Top Sector Life Sciences & Health and Asceneuron.
Board of Directors (continued)
33
Birgit Stattin Norinder (2012)Prolifix Ltd, Pharmacia & Upjohn, Glaxo Group Research Ltd.
Per Olof Wallström (2011)Merck, Astra, Pharmacia and Bristol-Myers Squibb, Q-Med AB, Melacure Therapeutics AB, Karo Bio AB and Camurus AB.
Dr. Stina Gestrelius (2007)Biora AB, Medicon Valley Alliance, BioActive Polymers, Biogaia AB (publ.), Clavis Pharma ASA (publ.) and Lipopeptide AB.
Prof. Gunnar Tufveson(Chairman) M.D., Ph.D., Professor of
Transplant Surgery at Uppsala University and Chief Physician at the Department of
Surgical Sciences at Uppsala University Hospital
Prof. Robert MontgomeryM.D., Ph.D., FACS, Director at NYU Langone Transplant Institute, New York, NY, USA
Prof. Stanley Jordan(Chairman) M.D., Ph.D., Director of Kidney Transplantation and Transplant Immunology, Kidney and Pancreas Transplant Center and Director of Division of Pediatric and Adult Nephrology, Cedars-Sinai Medical Center, Los Angeles, California
Prof. Kathryn WoodPh.D. Fellow of the Academy of Medical Sciences, Professor of
Immunology in the Nuffield Department of Surgical Sciences,
University of Oxford, England, runs the Transplantation Research
Immunology Group
Prof. Christophe LegendreM.D., Ph.D. Professor at Paris
Descartes University and Head of the Adult Nephrology and Transplantation
unit at Necker Hospital in Paris.
USA Europe
Medical Advisory Board34
Additional IdeS related information and data
35
1. Jordan et al. The New England Journal of Medicine 2017;377:442-53 “IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation”
n engl j med 377;5 nejm.org August 3, 2017444
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
After administration ofimmune globulin
After administration ofimmune globulin
After administration ofimmune globulin
After administration ofimmune globulin
— 250— 150— 100— 75
— 50— 37
— 20
— 150— 100
— 20
Anti-Fab
Anti-Fc
A Cleaving of Intact IgG by IdeS
C SDS-PAGE and Western Blot Analyses of Serum Samples D Effect of IdeS on Circulating IgG Levels in Highly Sensitized Patients
B Immunosuppressive Regimens
6 Mo
SwedenIgG
IdeS IdeS
scIgG F(ab′)2 and Fc
UnitedStates
Assessment of donor-specificantibodies and safety
Assessment of donor-specificantibodies and safety
Tacrolimus+MMF+glucocorticoids
Tacrolimus+MMF+glucocorticoids
Cross-matching
IdeS
Horse ATG
Transplantation of kidney fromdeceased or living donor
6 Mo
IdeS
Transplantation of kidney fromdeceased donor
>1 MoBefore
Before
treatm
ent1 h
r6 h
r
Patient 1
24 hr
7 day
s
21 day
s
30 day
s
— 250 — 150— 100— 75
— 50— 37
— 20
— 150— 100
— 20
Anti-Fab
Anti-Fc
Before
treatm
ent1 h
r6 h
r
Patient 2
24 hr
7 day
s
21 day
s
30 day
s
— 250— 150— 100— 75
— 50— 37
— 20
— 150— 100
— 20
Anti-Fab
Anti-Fc
Before
treatm
ent1 h
r6 h
r
Patient 3
24 hr
7 day
s
21 day
s
30 day
s
— 250— 150— 100— 75
— 50— 37
— 20
— 150— 100
— 20
Anti-Fab
Anti-Fc
Before
treatm
ent1 h
r6 h
r
Patient 4
24 hr
7 day
s
21 day
s
30 day
s
IgG
25
25 25
25
25 25
25
25
F(ab′)2
scIgG
IgG
F(ab′)2
scIgG
IgG
F(ab′)2
scIgGIgG
F(ab′)2
scIgG
IgG
Con
cent
ratio
n in
Ser
um (g
/lite
r)14
12
10
8
4
6
2
0
Before
Treatm
ent
0.5 H
r1 H
r2 H
r4 H
r6 H
r8 H
r1 D
ay
2 Day
s
3 Day
s
7 Day
s
14 D
ays
21 D
ays
28 D
ays
64 D
ays
P<0.001
P<0.001
kD kD
kD kD
CDC negative, ADCC positive or negative
CDC positive,ADCC positive
CDC negative,ADCC negative
Complement positive,Fcγ receptor positive
Complement negative,Fcγ receptor positive
or negative
Complement negative,Fcγ receptor negative
Cross-matching
Immune globulinand rituximab
Immune globulinand rituximab
Alemtuzumab — 4 days after transplantation
36
NEJM publication – IdeS effectively eliminates IgG in all 25 patients1
NEJM publication – IdeS effectively eliminates anti-HLA antibodies1
1. Jordan et al. The New England Journal of Medicine 2017;377:442-53 “IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation”
n engl j med 377;5 nejm.org August 3, 2017448
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
Subsequent assessments of SDS-PAGE, total IgG, and Western blot analyses of patients’ serum specimens obtained before and after treatment with IdeS were performed. SDS-PAGE analysis of serum specimens revealed reductions in the to-tal IgG level beginning after the infusion of IdeS (Fig. 1C). By 6 hours after the start of the infu-sion, all the IgG molecules are completely cleaved into Fc and F(ab′)2 fragments, which probably reduces their pathogenicity.19 All the IgG mole-cules are inactivated for approximately 1 to 2 weeks, when new IgG synthesis is detected.19 The large bands shown in the IgG region at 21 to 30 days occurred after the receipt of intravenous infu-
sions of immune globulin. Western blot analysis confirmed the complete cleavage of IgG mole-cules into Fc and F(ab′)2 fragments. Figure S2 in the Supplementary Appendix shows the dynamics of total IgG, Fc, and F(ab′)2 fragments in the serum specimens obtained from 10 IdeS-treated patients, as measured with the use of ELISA techniques. Intact IgG levels begin to decline rapidly; little intact IgG was present at 6 hours after treatment with IdeS. No intact IgG was seen at or after 7 days. Figure 1D shows the serum IgG levels after treat-ment with IdeS in 10 patients in the Swedish study. There was a significant reduction in the total IgG level that persisted for 28 days.
Figure 2. Levels of HLA Antibodies and C1q-Binding HLA Antibodies after IdeS Administration.
IdeS was used to reduce levels of pathogenic HLA antibodies and C1q-binding HLA antibodies as part of a dose-finding study involving eight patients with end-stage renal disease in Sweden. Panels A and B show the levels of HLA antibodies binding to 97 different HLA antigens. Each tick mark on the x axis indicates a single HLA antigen. Panel A shows the levels of HLA antibodies in a representative patient before and 6 hours after treatment with IdeS at a dose of 0.25 mg per kilogram of body weight. Levels were assessed with the use of the Luminex class I HLA an-tibody LABScreen single-antigen assay. Significant reductions in binding to all HLA antigens were observed. Panel B shows a similar analysis of the C1q-binding HLA antibodies (results are from the C1qScreen single-antigen assay). Complete or near-complete elimination of C1q binding was observed in samples obtained 1 hour after treatment.
Mea
n Fl
uore
scen
ce In
tens
ity
25,000
20,000
15,000
5,000
0
10,000
Single HLA Antigens (N=97)
Before treatmentAt 6 hr after treatment
B C1q-Binding HLA-Antibody Levels before and 1 Hr after Treatment
A HLA-Antibody Levels before and 6 Hr after TreatmentM
ean
Fluo
resc
ence
Inte
nsity
30,000
20,000
0
10,000
Single HLA Antigens (N=97)
Before treatmentAt 1 hr after treatment
37
Highdes Phase II - Study outline (ongoing)38
DD or LD Tx
ATGAM or Alemtuzumab
IdeS
6 mo
Tac+MMF+Steroids
DSA/safety
CXM
IVIg/Rituximab
1 wk
Study outline› Primary objective· IdeS efficacy in creating a negative crossmatch test
› Secondary objectives· DSA levels· Time to negative crossmatch· Safety parameters and kidney function· PD, PK, ADA
› 1(-2) doses· 0.25 (0.5) mg/kg
› Per-protocol medication· IVIg (d7)· Rituximab (d9)· ATGAM or Alemtuzumab induction · Loratadin (d1)· Corticosteroids (d1)
› 6 months follow up
Patient population› 18 crossmatch positive patients with LD or DD (Aim
15-20 patients)› Patients have previously undergone desensitization
unsuccessfully or effective desensitization will be highly unlikely
› 3 US study sites and 2 EU study sites› Enrollment finalized Jan 4, 2018. Final results
expected end of Q3 2018
Median years on kidney transplant waitlist (US)
Note: 1) US OPTN /SRTR 2012, 2011 Annual Data. 2) Primary research
39
HLA-sensitized patients by PRA1,2
By blood type2
PRA 20<80%
4.76
PRA 1-19% PRA 80-100%PRA<1%
2.89 3.09
Type 0 or B
2.50
5.50
Type A
1.00
Type AB
?
High medical need for kidney transplantationBuild up of patients in need of kidney transplantation in the US
Source: USRDS Annual Data Report 2016, US HHS Organ Procurement and Transplantation NetworkNote: 5-year CAGRs (until 2016 for waiting list and transplantations; 2014 for rest). 1) End stage renal disease
800,000
600,000
200,000
0
400,000
1,000,000
# patients
100,000
Patients on dialysis
700,000
Number of patients being transplanted
19,000
Kidney waiting list
500,000
Patients with ESRD1
+4%/yr
+4%/yr
+4%/yr+3%/yr
40
IdeS in anti-GBM antibody disease
› Rare acute kidney disease affecting 1/1,000,000 per year
› Continued enrollment in the investigator initiated Phase II study with IdeS in anti-GBM.
› As of March 31, seven patients had been included in the study. Approximately 15 patients will be recruited in the investigator initiated study at up to 15 clinics in Europe.
› Limited follow-up data is currently available from five of these seven patients who have responded favorably. IdeS appears to be well tolerated in these patients so far.
› Patients enrolled in the study will be monitored for six months.
› The primary objective of this study is to evaluate the safety and tolerability of IdeS as well as efficacy assessed by evaluating renal function at six months after IdeS treatment.
41
Status
› Drug substance (DS) /drug product (DP) currently used for clinical trial is a frozen 10 mg/mL solution
› The DS and DP processes have been developed and transferred to manufacturers suitable for commercialization
› The DP will be a lyophilized product
Ongoing and planned
› First GMP batch for clinical trials and commercial supply produced in late 2017
› Process characterization and validation for commercial is scheduled to be completed 2018
42
IdeS CMC overview
Guillain-Barré syndrome
Source: 1) McGrogan et al. Neuroepidemiology 2009;32(2):150-63. Note: 2) Seven major markets – US, Germany, UK, France, Spain, Italy, and Japan
43
› GBS is an autoimmune attack on the peripheral nervous system, which rapidly and progressively weakens extremities· 40% lose strength and have pain; 3-7% mortality
› Can affect anyone, at any age› Addressable population of 11,0001 per year in 7MM2
Indication overview
› Current SOC is treatment with IVIG or PE› Only parts of the patients fully recover from GBS,
thus a high unmet need for new treatments
Treatment options
Time from onset of weakness (weeks)
Course of GBS
Antibodies
Infection
Para
lysis
No w
eakn
ess
-4 0 4 8 12
Time from onset of weakness (weeks)
Course of GBSAntibodies
Infection
Para
lysis
No w
eakn
ess
-4 0 4 8 12
PLEX/IVIg
Potential with IdeS
Acute kidney AMR
Source: 1) Puttarajappa et al., Journal of Transplantation, 2012, Article ID 193724. 2) Jordan et al., British Medical Bulletin, 2015, 114:113-125. 3) http://www.irodat.org. Note: 4) Seven major markets – US, Germany, UK, France, Spain, Italy, and Japan
44
› Acute antibody mediated rejection after transplantation is a significant challenge to long term graft survival
› Occurring in ~10-15% of kidney transplants1
› Addressable population of 3,2002,3 in 7MM4
Indication overview
› There are no approved drugs for treatment of AMR; PE and steroids are primarily used today
› AMR patients not treated successfully risk graft failure, dialysis and return to transplantation waitlist
Treatment options
› IdeS treatment of AMR is a quick and effective method to inactivate donor specific antibodies and we expect this to translate into a clinical benefit for the patient
IdeS opportunity
ABOi kidney transplantation
Source: 1) Internal report. 2) Lipshutz, McGuire, Zhu et al., Arch Surg. 2011 Apr;146(4):453-8. Note: 3) Seven major markets – US, Germany, UK, France, Spain, Italy, and Japan
45
› Desensitization protocols are used in ABO incompatible transplant to lower antibodies to blood group antigens
› ABOi transplantation increases the donor pool› Addressable population of >2,6001 per year in 7MM3
Indication overview
› SoC: combinations of antibody removal by PE or IA, rituximab and standard triple immunosuppression2
› Current protocols are often cumbersome, time consuming and not suitable for deceased donor transplantation
Treatment options
› Strong scientific rationale due to an significant role of IgG
› Strong clinical rationale with high likelihood of success
IdeS opportunity
Heart transplantation
Note: 1) Chih et al. The Journal of Heart and Lung Transplantation, Vol 35, No 8, August 2016. 2) Seven major markets – US, Germany, UK, France, Spain, Italy, and Japan
46
› Presence of donor specific anti-HLA antibodies in the patient means transplantation cannot be carried out without antibody mediated rejection (AMR)
› Addressable population of 6501 per year in 7MM2
Indication overview
› Deferral of transplantation or desensitization by PE (experimental protocol – no approved methods)
› High unmet need as heart transplant has an overall low long-term survival rate, while AMR rejection is associated with higher morbidity and mortality compared to other rejection types
Treatment options
› IdeS can enable heart transplantation by removing donor specific antibodies - similar to kidney transplantation
IdeS opportunity
Lung transplantation
Note: 1) Chih et al. The Journal of Heart and Lung Transplantation, Vol 35, No 8, August 2016. 2) Seven major markets – US, Germany, UK, France, Spain, Italy, and Japan
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› Presence of donor specific anti-HLA antibodies in the patient means transplantation cannot be carried out without antibody mediated rejection (AMR)
› Addressable population of 5501 per year in 7MM2
Indication overview
› Deferral of transplantation or desensitization by PE (experimental protocol – no approved methods)
› High mortality rates on waiting lists
Treatment options
› IdeS can enable lung transplantation by removing donor specific antibodies - similar to kidney transplantation
IdeS opportunity
EnzE – IdeS in oncology
› Enzyme based antibody enhancement through pre-treatment
› The abundance of normal IgG in blood interferes with therapeutic monoclonal antibodies
› Pre-treatment with IdeS/NiceR has potential to potentiate antibody based cancer therapies· Growing market – targeted therapies are already
increasingly replacing existing chemotherapies
› Currently in preclinical development
Source: 1) Sofia Järnum et al. Enzymatic Inactivation of Endogenous IgG by IdeS Enhances TherapeuticAntibody Efficacy. Mol Cancer Ther 2017;16:1887-1897
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IdeS
EnzE PoC has been demonstrated in vivo for mice
› Study design· Mice (SCID) were injected intraperitoneally
with either, IVIg or IVIg and 3x IdeS· Rituximab (RTX) treatment was started on
day 14 after tumor cell inoculation (palpable tumors), once a week
› Outcome· The suppressive effect of IVIg on effector cell
function is abrogated by IdeS· IdeS can significantly improve the therapeutic
effect of rituximab
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10 15 20 25 300
500
1000
1500
Days after inoculation
Tum
or v
olum
e (m
m3 )
RTX start
No treatment
Rituximab
IdeS+Rituximab
Mice with human IgG (≈9 mg/mL)
NiceR – treating more indications by enabling repeat dosing› Hansa is developing NiceR – novel IgG
cleaving enzymes with lowered immunogenicity for repeat dosing
› NiceR broadens the indication space to reoccurring acute conditions, e.g. relapses in auto-immune diseases or reoccurring AMR
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Development of the two NiceRprojects are run in parallel
NICP· Generate an IgG cysteine peptidase
based on the amino acid sequence of IdeZ, a homolog to IdeS – already from start less immunogenic· Currently developed to improve
activity against IgG· A production process is under
development
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TRICP· “Molecular stealth technology” to
avoid the immune system· Generate variants of IdeS molecules
less immunogenic but with retained enzymatic activity compared to IdeS· For TRICP, drug candidates are
modified and evaluated
Strong patent protectionExpected year of expiry for each family
Note: 1) Includes additional term from PTA. 2) Assumes maximum 5 year SPC / PTE term is awarded in each territory
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2021 2023 2025 2027 2029 2031 2033 2035 2037
Dose Regime
IdeS - Medical Use
Dose Regime
IdeS - Medical Use
Dose Regime
IdeS - Medical Use
Expiry YearNormal patent term Supplementary protection / PTE
1
2
Competitive landscape› Hansa Medical is the first company developing IgG eliminating enzymes
› No FDA/EMA-approved methods for desensitization
› Some clinics use experimental protocols based on plasmapheresis, IVIG (e.g. Gammagard®, Baxalta/Shire plc) or rituximab (e.g. Rituxan®, Genentech Inc.), or combinations thereof
› Usually, such protocols require pre-treatment for days or weeks and are therefore mostly applicable in living donor transplantation
› No FDA/EMA approved methods for ABMR. Plasmapheresis and steroids is primarily used today. Some clinics also use Soliris®, Alexion Pharmaceuticals Inc. and/or rituxan. Shire plc is running a Phase III study in ABMR with Cinryze®.
› No FSA/EMA-approved methods for treatment of anti-GBM. Standard of care in the acute phase: plasmapheresis, steroids and cyclophosphamide.
› ABOi transplantation possible today with plasmapheresis in living donor transplantation but very limited in deceased donor transplantation.
› Standard-of-care for Guillain-Barré syndrome: Plasmapheresis or IVIG
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Pipeline with blockbuster potential54
Candidate / Method / Project 1 Indication
Research/Preclinical Phase I 2 Phase I/II Phase II Pivotal Registration
THERAPEUTICS
IdeS Kidney transplantation in highly sensitized patients 3
Anti-GBM antibody disease
Antibody mediated kidney transplant rejection (AMR)
Guillain-Barré syndrome
NiceR Recurring treatment in autoimmune disease,transplantation and oncology
EnzE Cancer immunotherapy
DIAGNOSTICS
HBP-assay (IVD) 4 Prediction of severe sepsis
n Planned n Ongoing n Completed
1) The EndoS project has been deprioritized and is put on hold.2) Present and future IdeS Phase II studies to be based on the same Phase I study. Results from the Phase I study have been published, Winstedt el al. (2015) PLOS ONE 10(7).3) Two separate Phase II studies with IdeS in highly sensitized patients are currently ongoing.4) Out-licensed to Axis-Shield Diagnostics Ltd.
