Jefferies Global Healthcare Conference, June 2015 Robert Kirkman, MD, President and CEO Julie Eastland, CFO

Transcription

1 Jefferies Global Healthcare Conference, June 2015 Robert Kirkman, MD, President and CEO Julie Eastland, CFO Copyright 2015 Oncothyreon

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 forwardlooking 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 The company undertakes no obligation to update the forwardlooking statements contained herein or to reflect events or circumstances occurring after the date hereof. 2 Copyright 2015 Oncothyreon

3 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 3 rd 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 3 Copyright 2015 Oncothyreon

4 Oncothyreon Oncology Product Pipeline Clinical Programs DISCOVERY PRE- CLINICAL PHASE 1 PHASE 2 PHASE 3 ONT-380 (Small Molecule) HER2+ Breast ONT-10 (Immunotherapy) Breast Ovarian Research Programs Chk1 Inhibitor (Small Molecule) Protocells Oncology Rare Diseases Immunotherapy (Antibody) Oncology Licensed from Array BioPharma Licensed from Sentinel Oncology Research Collaboration with Adimab LLC 4 Copyright 2015 Oncothyreon

5 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 5 Copyright 2015 Oncothyreon

6 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 Improved tolerability positions ONT-380 as the preferred drug to combine with other HER2-targeted agents or chemotherapy Potential for improved CNS activity ONT-380 shows superior activity compared with lapatinib and neratinib in CNS tumor models Superior CNS activity and drug tolerability supports evaluation of ONT-380 in treating this key unmet medical need 6 Copyright 2015 Oncothyreon

7 HER2+ Breast Cancer Treatment Paradigm - Where Does ONT-380 Fit? Neoadjuvant Surgery+/- radiation Adjuvant Metastatic first line Metastatic second line Metastatic third line or greater 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 7 Copyright 2015 Oncothyreon

8 Major Market Potential for 3 rd Line Metastatic and Metastatic CNS HER2+ Breast Cancer Third line metastatic disease 2014 GlobalData a 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 mets b - 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 a HER2 Positive Breast Cancer - Global Forecast , September 2014 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: Copyright 2015 Oncothyreon

9 ASCO 2015 Data Presentations 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 Hamilton a,b, Denise A. Yardley a,b, Gabriel Hortobagyi c, Luke Walker d, Virginia F. Borges e, Jorge Chaves f, Alison Conlin g, Stacy Moulder c a Sarah Cannon Research Institute, Nashville, TN; b Tennessee Oncology, Nashville, TN; c MD Anderson Cancer Center, Houston, TX; d Oncothyreon Inc., Seattle, WA; e University of Colorado Cancer Center, Aurora, CO, f Northwest Medical Specialities, Tacoma, WA, g Providence Cancer Center, Portland, OR ONT-380 in the Treatment of HER2+ Breast Cancer Central Nervous System (CNS) Metastases (Mets) Cristiano Ferrario a, Stephen Welch b, Jorge Chaves c, Luke Walker d, Ian Krop e, Erika Hamilton f,g, Virginia Borges h, Stacy Moulder i a Segal Cancer Centre -Jewish General Hospital, Montreal, Quebec; b London Regional Cancer Program, London Health Sciences Centre, London, Ontario; c Northwest Medical Specialties, Tacoma, WA; d Oncothyreon Inc., Seattle, WA; e Dana-Farber Cancer Institute, Boston, MA f Sarah Cannon Research Institute, Nashville, TN; g Tennessee Oncology, Nashville, TN h University of Colorado Cancer Center, Aurora, CO; i MD Anderson Cancer Center, Houston, TX; 9 Copyright 2015 Oncothyreon

10 Overview of ONT 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 mg PO BID (no food restrictions) Capecitabine 1000 mg/m 2 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 10 Copyright 2015 Oncothyreon

11 Patient Characteristics C (n = 7) ONT 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) Prior non-hormonal systemic treatments for metastatic disease, median (range) 3 (2-7) 4 (2-9) 3 (2-6) Trastuzumab (n) Pertuzumab (n) T-DM1 (n) Lapatinib (n) History of CNS metastases (n) Prior treatment for CNS metastases (n) Copyright 2015 Oncothyreon

12 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 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 12 Copyright 2015 Oncothyreon

13 Anti-tumor Activity Best overall response (RECIST 1.1) C (n =7 ) ONT T (n =13 ) C + T (n = 12) Evaluable patients, n CR cpr SD or non-cr non-pd a PD Too early to evaluate a. Includes pt with unconfirmed PR without follow-up scan 13 Copyright 2015 Oncothyreon

14 Change in Measurable Disease: ONT C + T 60% ONT Capecitabine +Trastuzumab Maximum Change in Sum of Longest Diamteters (%) 40% 20% 0% -20% -40% -60% -80% T,P,K T,L,K Prior treatment history T = trastuzumab L = lapatinib P = pertuzumab K = T-DM1 T,L,P,K T,P,K T,P,K T, K T,L,P,K T,K T,L,P,K -100% 14 Copyright 2015 Oncothyreon

15 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 : Phase 1b, open-label study of ONT T-DM1 (ado-trastuzumab emtansine) Population: Patients with HER2+ breast cancer with progression after prior therapy with both trastuzumab and a taxane ONT : 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 mg PO BID In combination with : T - DM 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 ONT Study 004 ONT Study Copyright 2015 Oncothyreon

16 ONT-380 in the Treatment of HER2+ Breast Cancer CNS Mets - 2 Definition of Response-Evaluable CNS Metastases 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 CNS Assessment 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 nontarget lesions 16 Copyright 2015 Oncothyreon

17 ONT-380 in the Treatment of HER2+ Breast Cancer CNS Mets - 3 Patients: 22 out of 68 patients had response-evaluable CNS metastases ONT T-DM1 C T C+T Total Patients enrolled (n) No history of CNS metastases (n) Stable treated CNS metastases (n) (not evaluable for CNS response) Response-evaluable for CNS metastases (n) Untreated asymptomatic Progression after prior CNS treatment (n) Copyright 2015 Oncothyreon

18 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 PR SD 3 4 a 6 5 b PD Not evaluable 2 c 0 1 d 0 Too early 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 18 Copyright 2015 Oncothyreon

19 Anti-tumor Activity Change in Measurable CNS Lesions 40% Untreated/Asymptomatic 40% Prior Local Therapy Best Response in Maximum Change in Sum of Longest Diameters (%) in CNS Metastases 20% 0% -20% -40% -60% -80% T T,P T,P + T-DM1 T,P T Best Response in Maximum Change in Sum of Longest Diameters (%) In CNS Metastases 20% 0% -20% -40% -60% -80% T,L,P T,L,P T,L,P T T,L,P T,P,L T + Capecitabine + Trastuzumab + Capecitabine + Trastuzumab + T-DM1-100% 3 pts not shown: 1 non-target lesions only, 2 without f/u CNS scans at time of systemic PD -100% 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 19 Copyright 2015 Oncothyreon

20 Anti-tumor Activity Case Study: Untreated/Asymptomatic CNS Metastases 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 Treatment: ONT T-DM1 MRI: Post 6 cycles: Complete resolution of target and non-target lesions in CNS (Images selected to demonstrate longest axis of lesions) 20 Copyright 2015 Oncothyreon

21 Anti-Tumor Activity Case Study: Progressive CNS Lesion after Local Therapy 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 Trastuzumab + Capecitabine MRI: Post 6 cycles: -60% reduction in CNS lesions (Images selected to demonstrate longest axis of lesions) Screening Post-cycle 6: 21

22 Summary and Conclusions from ASCO 2015 ONT 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 22 Copyright 2015 Oncothyreon

23 Protocells: A Nanoconstruct to Address Intractable Therapeutic Challenges 23 Copyright 2014 Oncothyreon

24 The Protocell Advantage Attributes Stability and Loading Targeting Safety and Immunogenicity Therapeutic Applicability Historical Challenges of Nanoconstructs Poor stability leads to cargo leakage and off-target toxicities Despite surface targeting ligands, previous constructs rely primarily on Enhanced Permeability and Retention (EPR) characteristics Increasing target ligand density for greater target specificity leads to greater immunogenicity Payloads limited in terms of chemical/molecular classes Protocell Solution 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 Fluid lipid bilayer with targeting ligands enables multivalent and cooperative binding to target cells, leading to a 100x improvement over similarly-targeted liposomes Targeting is achieved with a minimal number of ligands, thereby reducing unintended interactions and reducing immune profile Protocells deliver diverse cargos including small molecules, all nucleic acids (DNA, sirna, mrna), and peptides/proteins 24 Copyright 2014 Oncothyreon

25 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 Copyright 2015 Oncothyreon

26 Expected Milestones 2015 Expected Milestone Date ONT-380 Phase 1b update at ASCO Q2 15 ONT-380 Phase 2 trial initiation in MBC Q4 15 Protocell preclinical data Q4 15 ONT-380 Phase 1b T-DM1 data Q4 15 ONT-10 varlilumab combination trial data Q4 15 Protocell partnership Q Copyright 2015 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 Q Expanding product discovery capabilities Protocells in oncology and rare diseases Additional preclinical data expected H Business development opportunities Chk1 inhibitor Immunotherapy antibody discovery collaboration with Adimab Well funded Cash and investments -- $77.5 million at March 31, Copyright 2014 Oncothyreon