Jefferies Global Healthcare Conference, June 2015 · Opportunity to create cutting -edge products in oncology, immunotherapy, gene therapy and protein replacement Additional product

Jefferies Global Healthcare

Conference, June 2015

Robert Kirkman, MD, President and CEO Julie Eastland, CFO

Copyright © 2015 Oncothyreon

www.oncothyreon.com 2

Forward-looking Statements This presentation contains forward-looking statements, including statements concerning anticipated research, preclinical and clinical development activities, the potential benefits of proprietary technologies and product candidates, the potential of securing partnerships for development of protocell technology in new fields, potential market size and anticipated clinical milestone dates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, the possibility that preclinical and clinical trials of product candidates (including those using the protocell technology) will not be successful, or be completed, or confirm earlier results, risks associated with obtaining additional financing or funding from third parties, risks related to obtaining and protecting intellectual property rights, risks related to the timing and costs of preclinical development and clinical trials and the receipt of regulatory approvals and the other risk factors set forth in the company’s filings with the Securities and Exchange Commission and Canadian securities regulators, including the company’s Quarterly Reports on Form 10-Q and its Annual Report on Form 10-K for fiscal year 2014. The company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof.



Oncothyreon – Leading Oncology Product Candidates and Cutting-Edge Technology

ONT-380 – Potential best-in-class small molecule HER2 Inhibitor Positive data at ASCO 2015

Clinical activity in advanced stage patients Well-tolerated with no grade 3 diarrhea Responses in central nervous system metastases

Development plan in 3rd line MBC and potentially CNS metastases

Protocell technology places Oncothyreon at forefront of nanoparticle biosciences

Protocells offer potential best-in-class delivery technology for large molecules, from enzymes to nucleic acids Opportunity to create cutting-edge products in oncology, immunotherapy, gene therapy and protein replacement

Additional product opportunities ONT-10 – Phase 1b trial in combination with varlilumab Chk1 inhibitor – Collaboration with Sentinel Oncology Immunotherapy – Antibody discovery collaboration with Adimab


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Oncothyreon Oncology Product Pipeline

4 Copyright © 2015 Oncothyreon

DISCOVERY PRE- CLINICAL PHASE 1 PHASE 2 PHASE 3

Clinical Programs

Breast Ovarian

ONT-10 (Immunotherapy)

HER2+ Breast

ONT-380 (Small Molecule)

Licensed from Sentinel Oncology Licensed from Array BioPharma

Research Programs

Chk1 Inhibitor (Small Molecule)

Oncology

Immunotherapy (Antibody)

Oncology Rare Diseases

Protocells

Research Collaboration with Adimab LLC


Overview of HER2+ Breast Cancer

HER2: Member of the HER/EGFR receptor tyrosine kinase family Overexpressed in ~ 15-20% of all breast cancers Associated with increased mortality in early stage disease, decreased time to relapse, and increased incidence of metastases

HER2 targeted therapy in (neo)adjuvant and metastatic settings has led to marked and ongoing improvements in ORR, PFS and survival

Marketed agents include Herceptin®, Perjeta®, Kadcyla®, Tykerb® Modest single agent activity, best activity with combinations

Increased incidence of CNS metastases Up to 50% of patients with HER2+ metastatic breast cancer develop CNS metastases CNS was site of first recurrence in 13-14% of patients in CLEOPATRA trial in first line treatment of HER2+ metastatic breast cancer



ONT-380: The TKI of Choice for Use in HER2+ Breast Cancer

Exceptional potency and selectivity profile Single digit nanomolar potency for HER2 with 500-fold selectivity vs. EGFR Drug selectivity results in reduced incidence and severity of diarrhea/rash compared with lapatinib and neratinib

Potential for improved CNS activity ONT-380 shows superior activity compared with lapatinib and neratinib in CNS tumor models

Improved tolerability positions ONT-380 as the preferred drug to combine with other HER2-targeted agents or chemotherapy

Superior CNS activity and drug tolerability supports evaluation of ONT-380 in treating this key unmet medical need



HER2+ Breast Cancer Treatment Paradigm - Where Does ONT-380 Fit?

Current development plan focused on metastatic disease First line – Herceptin, Perjeta, docetaxel Second line – Kadcyla Third line – no preferred regimen: Opportunity for ONT-380 Prevention or treatment of CNS metastases: Opportunity for ONT-380

Potential additional opportunities Neoadjuvant Adjuvant Earlier metastatic treatment line

Neoadjuvant Surgery+/- radiation Adjuvant Metastatic

first line Metastatic

second line

Metastatic third line

or greater



Major Market Potential for 3rd Line Metastatic and Metastatic CNS HER2+ Breast Cancer

Third line metastatic disease 2014 GlobalDataa estimate for Stage IV, third line patients is 13,425 GlobalData estimate of Tykerb’s average annual US cost ~$60,000 Assuming 10% premium to Tykerb and comparable major market pricing Estimated addressable market for Stage IV 3rd line is ~$890M

HER2+ CNS Metastatic Disease 2014 GlobalData estimate for Stage IV patients is 67,127 Estimated Stage IV patients with brain metsb - 25% or 16,782 Similar pricing assumptions Estimated addressable market for CNS mets is ~$1.1B


Major markets are US, JP, GM, UK, FR, IT, SP

b Clayton AJ, Danson S, Jolly S, et al. Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 2004;91:639-643.

a HER2 Positive Breast Cancer - Global Forecast 2013-2023, September 2014


ASCO 2015 Data Presentations

ONT-380 in the Treatment of HER2+ Breast Cancer Central Nervous System (CNS) Metastases (Mets) Cristiano Ferrarioa, Stephen Welchb, Jorge Chavesc, Luke Walkerd, Ian Krope, Erika Hamiltonf,g, Virginia Borgesh, Stacy Moulderi

aSegal Cancer Centre -Jewish General Hospital, Montreal, Quebec; bLondon Regional Cancer Program, London Health Sciences Centre, London, Ontario; cNorthwest Medical Specialties, Tacoma, WA; d Oncothyreon Inc., Seattle, WA; eDana-Farber Cancer Institute, Boston, MA fSarah Cannon Research Institute, Nashville, TN; gTennessee Oncology, Nashville, TN hUniversity of Colorado Cancer Center, Aurora, CO; iMD Anderson Cancer Center, Houston, TX;

A Phase 1b Study of ONT-380, an Oral HER2-Specific Inhibitor, in Combination with Capecitabine (C) and Trastuzumab (T) in 3rd line+ Treatment of HER2+ Metastatic Breast Cancer (MBC) Erika Hamiltona,b, Denise A. Yardleya,b, Gabriel Hortobagyic, Luke Walkerd, Virginia F. Borgese, Jorge Chavesf, Alison Conling, Stacy Moulderc aSarah Cannon Research Institute, Nashville, TN; bTennessee Oncology, Nashville, TN; cMD Anderson Cancer Center, Houston, TX; dOncothyreon Inc., Seattle, WA; eUniversity of Colorado Cancer Center, Aurora, CO, fNorthwest Medical Specialities, Tacoma, WA, gProvidence Cancer Center, Portland, OR


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Overview of ONT-380 + Capecitabine (C) + Trastuzumab (T) Phase 1b Trial


Parallel 3+3 dose escalation of ONT-380 in combination with either C alone or T alone, followed by evaluation in combination with both C and T Selected Study Objectives

Evaluate safety of ONT-380 in combination with C and T Explore anti-tumor activity based on assessment of response by RECIST 1.1

Patient Population HER2+ breast cancer with progression after prior therapy with trastuzumab and T-DM1 for metastatic disease CNS disease -- Untreated asymptomatic metastases or progressive metastases after prior whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) allowed

Treatments 21 day cycle ONT-380 300 mg PO BID (no food restrictions) Capecitabine 1000 mg/m2 BID Days 1-14 Trastuzumab 8 mg/kg IV Cycle 1 Day 1, then 6 mg/kg q 21 days starting Cycle 2 Prophylactic anti-diarrheal medication not required

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Patient Characteristics


ONT-380 + C

(n = 7) T

(n = 13) C + T

(n = 12) Age, median (range) 54 (38-70) 49 (35-67) 48 (36-67) ECOG 0/1 (n) 3/4 5/8 8/4 Hormone receptor positive (n) 5 10 8 Prior non-hormonal systemic treatments for metastatic disease, median (range)

3 (2-7) 4 (2-9) 3 (2-6)

Trastuzumab (n) 7 13 12

Pertuzumab (n) 4 6 7

T-DM1 (n) 7 12 12 Lapatinib (n) 3 12 4

History of CNS metastases (n) 2 11 6 Prior treatment for CNS

metastases (n) 2 11 4

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Safety Overview

Majority of AEs Grade 1 or 2 in severity; no Grade 3 diarrhea

Most common AEs overall (in ≥5 pts) Diarrhea, nausea, constipation, fatigue, palmar-plantar erythrodysesthesia syndrome (PPE), vomiting, headache, dyspepsia, dizziness, hot flush, and arthralgia

11 SAEs overall 10 SAEs considered unrelated to study drugs 1 SAE in pt treated with ONT-380 300 mg BID + C + T considered related to both ONT-380 and capecitabine

Reversible Gr 4 edema at site of pre-existing untreated asymptomatic thalamic metastasis; considered possible treatment effect Considered a DLT; no other DLTs on study

No significant changes in left ventricular ejection fraction


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Anti-tumor Activity


ONT-380 + C

(n =7 ) T

(n =13 ) C + T

(n = 12) Best overall response (RECIST 1.1) Evaluable patients, n 7 11 9 CR 0 1 1 cPR 5 3 4 SD or non-CR non-PD 2 5 2a PD 0 2 2 Too early to evaluate 0 2 3

a. Includes pt with unconfirmed PR without follow-up scan

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Change in Measurable Disease: ONT-380 + C + T


T,P,K T,L,K T,L,P,K T,P,K T,P,K T, K T,L,P,K T,K T,L,P,K

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

60%

Max

imum

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f Lon

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Dia

mte

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(%)

ONT-380 + Capecitabine +Trastuzumab

Prior treatment history T = trastuzumab L = lapatinib P = pertuzumab K = T-DM1

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ONT-380 in the Treatment of HER2+ Breast Cancer CNS Mets - 1

Patients with response-evaluable CNS metastases were selected for inclusion in this case series from the following ongoing phase 1b studies:

ONT-380-004: Phase 1b, open-label study of ONT-380 + T-DM1 (ado-trastuzumab emtansine)

Population: Patients with HER2+ breast cancer with progression after prior therapy with both trastuzumab and a taxane

ONT-380-005: Phase 1b, open-label study of ONT-380 +/- capecitabine (C) and +/- trastuzumab (T)

Population: Patients with HER2+ breast cancer with progression after prior therapy with both trastuzumab and T-DM1


ONT - 380 300 mg PO BID

T - DM 1 3 . 6 mg / kg IV q 21 days

Capecitabine 1000 mg / m 2 PO BID

Cycle Days 1 - 14

Trastuzumab 8 mg / kg IV C 1 D 1 ;

6 mg / kg IV q 21 days

Capecitabine +

Trastuzumab

In combination with :

ONT - 380 Study 005 ONT - 380 Study 004

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CNS metastases were considered response-evaluable if they met either of the following criteria:

Untreated, asymptomatic lesions in patients who had never received radiotherapy or surgery to the CNS Progressive or new lesions in patients who had received previous radiotherapy and/or surgery to the CNS

Groups analyzed separately based on data suggesting lower CNS response rates to systemic tx in previously radiated pts Previously radiated lesions that did not have obvious progression were not considered response evaluable

CT scans and brain MRI at baseline and once every 6 weeks through cycle 6, then once every 9 weeks. Overall response assessment and treatment decisions per RECIST 1.1

CNS response defined as ≥30% decrease in sum of the longest diameter (SLD) of CNS target lesions (target lesions must be ≥1 cm) CNS progression defined as ≥20% increase from nadir and ≥5 mm absolute increase in the SLD of all target lesions, or unequivocal progression in non-target lesions

Definition of Response-Evaluable CNS Metastases

CNS Assessment

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ONT-380 + T-DM1 C T C+T Total

Patients enrolled (n) 36 7 13 12 68

No history of CNS metastases (n) 14 5 2 6 27

Stable treated CNS metastases (n) (not evaluable for CNS response) 10 1 6 2 19

Response-evaluable for CNS metastases (n) 12 1 5 4 22

Untreated asymptomatic 6 0 0 2 8

Progression after prior CNS treatment (n) 6 1 5 2 14

Patients: 22 out of 68 patients had response-evaluable CNS metastases

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Anti-tumor Activity


Untreated, Asymptomatic CNS Mets n=8

Progressive/ New CNS Mets after Tx n=14

Best Response CNS Only Overall CNS Only Overall

CR 1 0 0 0

PR 2 2 2 4

SD 3 4a 6 5b

PD 0 2 0 0

Not evaluable 2c 0 1d 0

Too early 0 0 5 5

a. Includes one pt with unconfirmed PR who went off study for AE of PPE b. Includes 1 pt with non-CR non-PD (i.e. has non-target lesions only) c. 2 pts with systemic PD but without follow up CNS scan on study d. 1 pt with increasing lesion taken off study for surgical resection; pathology revealed no viable tumor cells

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Anti-tumor Activity


Change in Measurable CNS Lesions

T,P,L T

T,L,P T,L,P T,L,P T T,L,P

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

Best

Res

pons

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Max

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iam

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) In

CN

S M

etas

tase

s

Prior Local Therapy

+ Capecitabine + Trastuzumab

+ Capecitabine

+ Trastuzumab

+ T-DM1

T T,P T,P T,P T

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

Best

Res

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Max

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in S

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s (%

) in

CN

S M

etas

tase

s

Untreated/Asymptomatic

3 pts not shown: 1 non-target lesions only, 2 without f/u CNS scans at time of systemic PD

7 pts not shown: 5 active patients who have not yet had first f/u MRI, 1 pt with non-target lesions only, 1 pt taken for surgical resection of increasing target lesion with no viable tumor found

+ T-DM1

Anti-tumor Activity

Patient History Previously treated with trastuzumab, paclitaxel and pertuzumab for 11 months Found to have new asymptomatic CNS metastases at the time of study screening No history of prior CNS radiation therapy

Case Study: Untreated/Asymptomatic CNS Metastases


Treatment: ONT-380 + T-DM1 MRI:

Post 6 cycles: Complete resolution of target and non-target lesions in CNS (Images selected to demonstrate longest axis of lesions)

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Anti-Tumor Activity

Patient History: Whole brain radiotherapy 21 months prior to study entry Progression of 4 of 5 known lesions while on lapatinib + cabazitaxel for 4 mos, just prior to study enrollment

Treatment: ONT-380 + Trastuzumab + Capecitabine

MRI:

Post 6 cycles: -60% reduction in CNS lesions (Images selected to demonstrate longest axis of lesions)

21

Screening Post-cycle 6:

Case Study: Progressive CNS Lesion after Local Therapy

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Summary and Conclusions from ASCO 2015


ONT-380 300 mg BID in combination with each of T-DM1, trastuzumab, capecitabine, or trastuzumab + capecitabine has been well tolerated in patients with HER2+ breast cancer

Majority of AEs were Grade 1 or 2 in severity, with no Grade 3 diarrhea

Encouraging signs of activity in both systemic and CNS metastases in a heavily pretreated population for all combinations evaluated

Clinical benefit and response seen in patients previously treated with trastuzumab, pertuzumab, T-DM1, or lapatinib

Decrease in size of target CNS lesions (up to 100%) seen in patients with and without prior history of CNS local therapy, with CNS tumor control of >6 months in some patients

Based on observed clinical benefit and responses seen, a Phase 2 study to further evaluate the activity of ONT-380 in combination with capecitabine and trastuzumab in patients with advanced HER2+ breast cancer with progression after pertuzumab and T-DM1 is planned

Further study of CNS activity of ONT-380 is warranted

www.oncothyreon.com Copyright © 2014 Oncothyreon

Protocells: A Nanoconstruct to Address Intractable Therapeutic Challenges

23

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The Protocell Advantage

Attributes Historical Challenges of Nanoconstructs Protocell Solution

Stability and Loading

Poor stability leads to cargo leakage and off-target

toxicities

Nano-silica core stabilizes drug product allowing outer, lipid layer to be functionalized for ideal in vivo behavior while carrying 1000x

the cargo of liposomes

Targeting

Despite surface targeting ligands, previous constructs rely primarily on Enhanced Permeability and Retention

(EPR) characteristics

Fluid lipid bilayer with targeting ligands enables multivalent and cooperative binding to target cells, leading to a 100x improvement over

similarly-targeted liposomes

Safety and Immunogenicity

Increasing target ligand density for greater target

specificity leads to greater immunogenicity

Targeting is achieved with a minimal number of ligands, thereby reducing unintended

interactions and reducing immune profile

Therapeutic Applicability

Payloads limited in terms of chemical/molecular classes

Protocells deliver diverse cargos including small molecules, all nucleic acids (DNA, siRNA,

mRNA), and peptides/proteins

24

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Protocell Platform – Planned 2015 POC Studies

Oncology – Improved risk/benefit Cargo: Cytotoxics, targeted small molecules and protein toxins with limited therapeutic windows Targeting: Tumor-associated antigens Goal: Show improved efficacy and superior therapeutic index; enable development of targeted toxins as superior alternative to ADC’s

Rare genetic diseases – gene replacement or modulation Cargos: Proteins/enzymes, mRNA, DNA Targeting

Liver for lysosomal storage diseases Tissue-specific receptors (non-liver targets)

Goal: Deliver protein replacement therapeutics in vivo for lysosomal and other genetic diseases

CAR T-cells – potential of in-vivo CAR T-cell transfection Cargo: Chimeric antigen receptor mRNA/DNA Targeting: T-cell specific receptors Goal: Show in vivo transfection of T-cells with reporters and CARs; initiate animal tumor models in 2H 2015



Expected Milestones – 2015


Expected Milestone Date

√

Q4 15

√

Protocell preclinical data

Protocell partnership Q4 15

ONT-10 varlilumab combination trial data Q4 15

ONT-380 Phase 1b T-DM1 data Q4 15

ONT-380 Phase 1b update at ASCO

ONT-380 Phase 2 trial initiation in MBC Q4 15

Q2 15 √

www.oncothyreon.com Copyright © 2014 Oncothyreon 27

Oncothyreon – The Investment Opportunity

ONT-380 – potential best-in-class small molecule HER2 inhibitor Clinical activity in advanced stage patients; no grade 3 diarrhea Exclusive license to develop and commercialize Phase 2 trial in third line metastatic breast cancer planned Additional data and CNS plan Q4 2015

Expanding product discovery capabilities Protocells in oncology and rare diseases

Additional preclinical data expected H2 2015 Business development opportunities

Chk1 inhibitor Immunotherapy antibody discovery collaboration with Adimab

Well funded Cash and investments -- $77.5 million at March 31, 2015

Documents

Jefferies Global Healthcare Conference, June 2015 · Opportunity to create cutting -edge products in oncology, immunotherapy, gene therapy and protein replacement Additional product