Jefferies Global Healthcare Conference - June 2014 Robert Kirkman, MD, President and CEO Julie Eastland, CFO

Transcription

1 Jefferies Global Healthcare Conference - June 2014 Robert Kirkman, MD, President and CEO Julie Eastland, CFO

2 Forward-looking Statement This presentation contains forward-looking statements, including statements concerning anticipated clinical development activities, the potential benefits of product candidates 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 clinical trials will not be successful, or be completed, or confirm earlier clinical trial results, risks associated with obtaining additional financing or funding from third parties, risks related to the timing and costs of 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 10Q 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

3 Oncothyreon Advancing Leading Oncology Product Candidates ONT-380 Potential best-in-class small molecule HER2 Inhibitor Highly selective for HER2 to minimize off-target side effects Active in HER2+ brain metastasis models Development plan focused on combination therapy for metastatic disease and patients with brain metastases Tecemotide First-in-class immunotherapy for non-small cell lung cancer 10.2 month median survival advantage in large sub-group (n=806) in Phase 3 trial Partner Merck Serono conducting 1,000 patient confirmatory Phase 3 trial ONT-10 Second generation immunotherapeutic Phase 1 data at ASCO demonstrates improved immunogenicity and prolonged stable disease in advanced stage patients Collaboration with Celldex for combination Phase 1b trial with varlilumab Fully owned by Oncothyreon 3

4 Oncology Product Pipeline Multiple approaches to target solid tumors Clinical Programs PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Tecemotide (Immunotherapy) NSCLC ONT-380 (Small Molecule) HER2+ Breast ONT-10 (Immunotherapy) Various Solid Tumors Adjuvant Technology PET-Lipid A Licensed to Merck KGaA Collaboration with Array BioPharma 4

5 Overview of HER2+ Breast Cancer HER2: Member of the HER/EGFR receptor tyrosine kinase family Overexpressed in ~ 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 Antibody and small molecule approaches Modest single agent activity, best activity with chemo combinations Two agents targeting HER2 better than one Treatment paradigm is evolving Development plan designed to position ONT-380 for the future of HER2 directed therapy Focus on potential competitive advantages of ONT-380 5

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 rash/gi toxicity compared with lapatinib and neratinib Improved tolerability positions ONT-380 as the preferred drug to combine with other HER2-targeted agents or chemotherapy 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

7 ONT-380 is the Only Selective HER2 Inhibitor in Clinical Development ONT-380 Compound ONT-380 Neratinib Lapatinib HER2 IC 50 (nm) 8 7 Cellular Selectivity Data EGFR IC 50 (nm) HER2 IC 50 (nm) 50% Human Serum

8 ONT-380 Active Alone and in Combination in Preclinical HER2+ Tumor Models ONT-380 (100 mg/kg, PO QD) ONT-380 (100 mg/kg) 8

9 ONT-380 Shows Superior Activity in Preclinical CNS Tumor Model ONT-380 produced superior therapeutic benefit compared with lapatinib and neratinib in mice bearing intracranial HER2+ tumors BT-474 HER2+ breast carcinoma ONT-380 (75 mg/kg, BID PO) 9

10 ONT-380 Is Active In Heavily Pretreated Patients Phase 1 Trial Partial responses observed in 3/22 (14%) of heavily pre-treated HER2+ patients dosed 600mg BID PR + SD 6 months in 6/22 (27%) of patients dosed 600mg BID Investigator Assessment PR PRu SD 6 months PR+SD 6 months PR+Pru+SD 6 months ONT-10 Dose (mg BID), HER2+ MBC Pts with measurable disease (n) 600/650 N= N=4 1* Total n=22 % *ONT-380 was held after 4 days of dosing due to DLT and then restarted at 600 mg BID, Pru_Unconfirmed PR All 3 PRS had confirmed progression on trastuzumab and 2 had progressed on lapatinib No treatment related Serious Adverse Events or discontinuations due to Adverse Events 10

11 ONT-380 Clinical Safety Treatment Related Adverse Events ( 10% Patients) 200 mg n = mg n = 3 ONT-380 Dose (BID)* 500 mg n = 4 600/650 mg** n = mg n = 4 Total (25 to 800 mg BID) n = 50 (%) Grade Nausea Diarrhea (28) 10 (20) 3 (6) 0 (0) 1 (2) 0 (0) Fatigue (8) 6 (12) 0 (0) Elevated AST and/or ALT (0) 3 (6) 3 (6) Combined Rash*** (18) 0 (0) 1 (2) Vomiting (10) 1 (2) 0 (0) * AEs reported at doses of 25 mg BID (n = 3), 50 mg BID (n = 3) and 100 mg BID (n = 3) are only presented as part of the total column. ** The 650 mg BID dose was modified to 600 mg due to lack of availability of 25 mg capsules (650 mg BID [n = 3]; 600 mg BID [n = 24]). *** Combined rash includes events of rash, maculopapular rash, skin exfoliation, dermatitis acneiform and pruritic rash. 11

12 Positioning ONT-380 in the HER2+ Breast Cancer Treatment Paradigm Neoadjuvant Surgery+/- radiation Adjuvant Metastatic first line Metastatic second line Metastatic third line or greater Identify new strategies to target CNS metastases Treatment of existing CNS metastases Three ongoing trials include patients with CNS metastases Potential registration strategy Prevention of CNS metastases 30% or more of patients with HER2+ metastatic breast cancer eventually develop CNS metastases Identify better tolerated and more effective combination therapies Exploit better side effect profile to support long term drug regimens Potential to overcome resistance to HER2 inhibition Ongoing trials in combination with HER2 targeted agents and chemotherapy 12

13 ONT-380 Ongoing Trials to Enable Development Strategy in Metastatic Disease, including Brain Metastases Phase 1b in combination with TDM-1 (Kadcyla ) Dose escalation in patients previously treated with Herceptin and a taxane to determine MTD/RP2D Includes patients with brain metastases Up to 48 patients including expansion cohorts Phase 1b in combination with trastuzumab (Herceptin ) and/or capecitabine (Xeloda ) Study includes both combinations and triplet Includes patients with brain metastases Up to 50 patients including expansion cohorts Phase 1 in combination with trastuzumab in patients with brain metastases Investigation sponsored by Dana-Farber Cancer Institute Up to 50 patients 13

14 ONT-380 Overview of Collaboration between Oncothyreon and Array Oncothyreon will conduct defined set of proof of concept Phase 1b and Phase 2 studies Oncothyreon and Array will share in development after proof of concept studies Mechanism for Oncothyreon to recap percentage of proof of concept costs Array responsible for commercialization worldwide Oncothyreon has 50% co-promote right in US, with 50/50 profit share Royalty to Oncothyreon on net sales ex-us, intended to approximate 50/50 profit share Oncothyreon and Array share equally proceeds from any third party license ex-us 14

15 Tecemotide and ONT-10 the Future of Immunotherapy Targeting MUC1 Tecemotide Licensed to Merck KGaA START demonstrated 10.2 month median survival advantage in Stage III NSCLC patients with concurrent chemo-radiation Merck Serono has initiated START2 a 1000 patient Phase 3 trial based on subgroup analysis ONT-10 Proprietary to Oncothyreon Validated target Potential for improved mechanism of action Phase 1 data demonstrate strong antibody response and encouraging clinical data 15

16 Pivotal Phase 3 START Trial (Merck KGaA) 16

17 OS rate, % Primary Endpoint Overall Survival Updated at ESMO Updated at ESMO 17

18 OS rate, % Overall Survival in Concurrent Chemo-Radiotherapy Updated at ESMO Updated OS (concomitant chemo/rt) 18

19 What Does START Mean Going Forward for Tecemotide and ONT-10? MUC1 is a valid target 10.2 month statistically significant survival advantage in predefined subgroup 806 patient subgroup is largest trial in Stage III lung cancer The future for tecemotide Merck Serono committing significant resources to START2 Large market opportunity Up to $90 million in milestones plus royalties ranging from midteens to high single digits, depending on territory The future for ONT-10 Potentially improved vaccine Opportunity to leverage lessons from START Fully owned by Oncothyreon 19

20 ONT-10: The Next Generation Proprietary liposomal microparticle formulation Simple to manufacture, scalable Glycosylated MUC1 peptide antigen Modified antigen designed to produce cellular and humoral immune response Better mimics tumor-associated MUC1 PET Lipid A adjuvant Fully synthetic product with improved potency versus MPL 20

21 ONT-10: A Two Part, Phase 1 Trial Study Design Part 1 Part 2 Endpoints Dose escalation schedule in 49 patients to determine maximally tolerated or recommended (MTD/RD) dose of ONT-10 Administered weekly or every other week for 8 weeks Patients have Stage 3 or 4 MUC1 expressing tumors Enrollment complete To enroll expansion cohorts of up to 15 patients each at MTD/RD Primary endpoint is safety Secondary endpoint is level of immune response to the vaccine Antibody response T-cell response Exploratory analysis of clinical response 21

22 ONT-10 Generates Robust Antibody Response Against MUC-1 22

23 ONT-10 Disease Control 72% of patients eligible for maintenance study 31/43 response-evaluable patients without progression by immune-related response criteria (irrc) after at least 12 weeks on induction study 11 patients on treatment without progression for > 6 months (range months) Ovarian/primary peritoneal (n=3); breast (n=2); NSCLC (n=2); endometrial, prostate, cervical, and colorectal (n=1 each) 2 ovarian cancer patients with nodal shrinkage 16% decrease (RECIST 1.1) at Week 9 (ovarian cancer, 500 µg Q2W) 44% decrease (irrc) at maintenance cycle 4 (ovarian cancer, 500 µg QW) 23

24 ONT-10 Overall Time on Treatment for 31 Patients in Maintenance Study 180 days Active 24

25 ONT-10 Next Steps Taking Advantage of the Opportunity Expanding Phase 1 trial in disease-specific indications Breast cancer Ovarian cancer Phase 1b combination trial of ONT-10 and varlilumab Breast and ovarian cancer Collaboration with Celldex Therapeutics Varlilumab (CDX-1127) targets CD27, a critical molecule in the activation pathway of lymphocytes Fully human agonist monoclonal antibody Combinations of immune modulating therapies likely represent the future of immunotherapy 25

26 2014 Clinical Milestones Expected Milestone Date ONT-380 Phase 1b trial initiations Tecemotide START2 initiation ONT-10 Phase 1 data update at ASCO ONT-380 Phase 1b trial data ONT-380 Phase 2 trial initiation ONT-10 Phase 2 trial initiation Q1 14 Q2 14 Q2 14 Q4 14 Q4 14 Q

27 Oncothyreon The Investment Opportunity ONT-380 potential best in class small molecule HER2 inhibitor Highly competitive safety profile Potential to treat or prevent brain metastases Phase 1b data Q Tecemotide START data validates MUC1 target 10.2 month statistically significant survival advantage in 806 patient pre-specified subgroup Confirmatory Phase 3 trial START2 underway ONT-10 Follow-on vaccine targeting MUC1 Novel adjuvant and improved mechanism of action Phase 1 data encouraging antibody response and disease control Planned Phase 1b combination trial with varlilumab Fully owned by Oncothyreon Well funded cash $64.3 million at 3/31/14 27