Oncolytic Virotherapy Summit. December 3, 2015

Transcription

1 Oncolytic Virotherapy Summit December 3, 2015

2 Forward Looking Statements This presentation contains certain forward looking statements relating to the company s financial results, business prospects and the development and commercialization of REOLYSIN, a therapeutic reovirus. These statements are based on management s current expectations and beliefs and are subject to a number of factors which involve known and unknown risks, delays, uncertainties and other factors not under the company s control which may cause actual results, performance or achievements of the company to be materially different from the results, performance or other expectations implied by these forward looking statements. In any forward looking statement in which Oncolytics Biotech Inc. expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. These factors include results of current or pending clinical trials, risks associated with intellectual property protection, financial projections, market projections, actions by the FDA/HPB/MHRA and those other factors detailed in the company s filings with SEDAR and the Securities and Exchange Commission. Oncolytics does not undertake an obligation to update the forward looking statements, except as required by applicable laws. 2

3 Oncolytics Overview Developing REOLYSIN (oncolytic virus) as a cancer therapeutic Conducted 30+ clinical studies in 13 indications Manufacturing at commercial scale 100L cgmp completed 400+ issued patents and 235 pending applications worldwide 1,100+ patients treated; strong safety profile $32.1 million cash as at the end of Q2,

4 What is REOLYSIN? Proprietary isolate of the reovirus Widely found Non-pathogenic Widespread human exposure 4

5 REOLYSIN and Safety General Safety 1,100+ patients treated, 1,000+ of these intravenously No MTD reached Safety profile confirmed in a randomized setting Monotherapy Safety Mild toxicities (grade 1 or 2) including Chills Fever Headache Cough Myalgia Runny nose Sore throat Fatigue Lymphopenia or neutropenia Transient grade 3 and 4 toxicities included lymphopenia or neutropenia symptoms usually last < 6 hours 5

6 REOLYSIN Clinical Program Indication Studies GLIOMA REO 003 Phase I/II REO 007 Phase I/II REO 008 Phase II NCI (COG-ADVL1014) Phase I REO 013 Brain Phase I MAY0 (MC-1472) Phase I Orphan Status PROSTATE REO 001 Phase I REO 002 Phase I IND 209 Phase II OVARIAN NCI (OSU-07022) Phase I/II NCI (GOG-0186H) Phase II Orphan Status COLORECTAL REO 022 Phase II IND 210 Phase II LUNG REO 014 Phase II REO 016 Phase II REO 021 Phase II IND 211 Phase II PANCREATIC REO 009 Phase I REO 017 Phase I/II NCI 8601 Phase II Orphan Status MYELOMA NCI (OSU-11148) Phase I NCI 9603 Translational REO 019 Phase I b MELANOMA NCI (MAYO MC0672 ) Phase II REO 020 Phase II HEAD AND NECK REO 004 Phase I REO 005 Phase I REO 011 Phase I/II REO 015 Phase II REO 018 Phase III BREAST BLADDER IND 213 Phase II REO 023 Run-In Study Ongoing Study Completed Study 6

7 REOLYSIN : Delivery to the Tumour Site When delivered intravenously as a monotherapy, REOLYSIN has been shown to be delivered to the interior of a tumour in: Colorectal cancer metastatic lesions to the liver Brain metastases from various primaries Primary gliomas and astrocytomas Ovarian cancer Multiple myeloma (the majority of cell tumour population in bone marrow lesions) 7

8 REOLYSIN : Reducing Tumour Burden

9 REOLYSIN Mechanism of Action Normal Cells Cellular stress event REOLYSIN Administer to patients PRE- SCREENED for RAS, EGFR, BRAF and others REOLYSIN infects both tumour cells and normal healthy cells REOLYSIN infects both tumour cells and normal healthy cells REOLYSIN does not replicate in cells that are not Ras activated Ras Activated Cells REOLYSIN replicates in Ras-activated tumour cells Healthy cells remain undamaged Tumour cells then rupture to release progeny virus REOLYSIN s ability to kill tumour cells is dependent upon the reovirus completion of its replication cycle. 9

10 REO 003: REOLYSIN Intratumoural Monotherapy Anaplastic Astrocytoma Early Cytotoxic Activity Followed by Late Stage Immune-Mediated Response Against the Residual Tumour Days after REOLYSIN administration: Viral replication mediated tumour response 10 Post debulking Immune mediated tumour response

11 REO 021: Partial Response in Patient with Squamous Cell Carcinoma of the Lung Right Upper Lung Mass (8.3 cm) Right Upper Lung Mass (4.1 cm) Right Upper Lung Mass (3.6 cm) Right Pleural Met (2.2 cm) Pre-Treatment Right Pleural Met (0.8 cm) Post-Cycle 2 Right Pleural Met (0.4 cm) Post-Cycle 4 11

12 REO 018 Head and Neck Cancer: Randomized Tumour-Specific Response Data First Endpoint: Velocity o 105 patients o 86% of test arm (n=50) had tumour stabilization or shrinkage o 67% of control arm (n=55) had tumour stabilization or shrinkage o p-value Second Endpoint: Volume Loco-regional patients with or without distal metastases o 23% improvement in test arm vs. control for tumour volume decrease o p-value 0.076, n=118 Patients with distal metastases only o 30% improvement in test arm vs. control for tumour volume decrease o p-value 0.021, n=47 Study demonstrated that REOLYSIN increased both the magnitude and velocity of tumour shrinkage 12

13 REOLYSIN Plus Carfilzomib Response Data in Multiple Myeloma % Change of Monoclonal Protein Patients Evaluable for Response Response as per International Myeloma Working Group (IMWG): Patients 1 & 2 = VGPR; Patients 3, 6 & 7 = PR; Patients 4, 5 & 8 = MR 13

14 Registration Program for REOLYSIN Tumour Reduction Endpoints: Neoadjuvant treatment of muscle-invasive bladder cancer Neoadjuvant = therapy used prior to a major therapeutic intervention (usually surgery) in order to improve outcome Muscle invasive bladder cancer is the only cancer indication in which US regulators have accepted histopathological response as a registration endpoint in a neoadjuvant study to date Each patient enrolled in the study will be assessable for this endpoint at a maximum of nine weeks after starting treatment Next Steps: IND has been filed to conduct a small run-in study assessing histopathological response in muscle invasive bladder cancer o REOLYSIN in combination with gemcitabine and cisplatin Subject to confirmation of response proceed to pivotal trial 14

15 REOLYSIN : Improving Overall Survival

16 REOLYSIN Mechanism of Action Normal Cells Cellular stress event REOLYSIN Administer to patients PRE- SCREENED for RAS, EGFR, BRAF and others REOLYSIN infects both tumour cells and normal healthy cells REOLYSIN does not replicate in cells that are not Ras activated Ras Activated Cells Healthy cells remain undamaged Progeny viruses repeat cell infection cycle in nearby tumour cells Tumour cells then rupture to release progeny virus REOLYSIN infects both tumour cells and normal healthy cells REOLYSIN replicates in Ras-activated tumour cells Productively infected cells upregulate interferon and others, including PD-1 and PD-L1, and induce an antitumour specific immune response mediated by T cells 16

17 REO 003: REOLYSIN Intratumoural Monotherapy Anaplastic Astrocytoma Early Cytotoxic Activity Followed by Late Stage Immune-Mediated Response Against the Residual Tumour Days Post Treatment: Viral replication mediated tumour response 17 Post debulking Immune mediated tumour response

18 Patient Outcomes Are Influenced By Immune Status The survival rate of ovarian cancer patients with high PD-L1 expression on entry is statistically significantly worse than that of patients with low PD-L1 expression on entry. Five year survival was 80.2% for patients with low PD-L1 expression on entry and 52.6% for those with high PD-L1 expression on entry (p = 0.016). Mean survival was 9.56 years for patients with low PD-L1 expression on entry and 6.48 years for those with high PD-L1 expression on entry. 1 The survival rate of ovarian cancer patients with high intraepithelial CD8 + T lymphocyte counts on entry is statistically significantly better than that of patients with low CD8 + T lymphocyte counts. Five year survival was 86.9% for patients with high CD8 + T lymphocyte counts on entry and 39% for those with low CD8 + T lymphocyte counts on entry (p < 0.001). Mean survival was 9.6 years for patients with high CD8 + T lymphocyte counts on entry was 9.6 years and 4.7 years for those with low CD8 + T lymphocyte counts on entry. 1 1 Hamanishi et al Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. PNAS 104(9):

19 REOLYSIN in Multiple Myeloma Variable REOLYSIN Monotherapy, Pre-Treatment REOLYSIN Monotherapy, Post-Treatment Statistics REOLYSIN + Carfilzomib, Pre- Treatment REOLYSIN + Carfilzomib, Post- Treatment Statistics CD (21.5) 63.9 (18.3) not significant 37.8 (8.5) 84.6 (26.8) p=0.060 PD-L (9.2) 30.6 (11.5) not significant 74.2 (49.5) (31.1) p=0.005 caspase (0.6) 6.2 (0.9) not significant 6.2 (0.8) 24.8 (4.3) p=0.005 Data supplied by Dr. J. Nuovo 19

20 Top-Line Overall Survival (OS) Results REO 017 (Pancreatic Cancer) Comparison with ACCORD 11 and MPACT Studies: Treatment n CA % Decrease from Baseline Median PFS (months) Median OS (months) 1-Year Survival (%) 2-Year Survival (%) Gemcitabine (ACCORD 11) (Conroy et al., 2011) 171 N/A Gemcitabine (MPACT) (Van Hoff et al., 2013) (Goldstein et al., 2015) Gemcitabine/REOLYSIN (REO 017)

21 Top Line Overall Survival (OS) Results REO 016 (Non-Small Cell Lung Cancer) Comparison with Schiller et al., 2002: Treatment n Median PFS (months) Median OS (months) 1-Year Survival (%) 2-Year Survival (%) Carboplatin and paclitaxel (Schiller et al., 2002) Carboplatin, paclitaxel and REOLYSIN (REO 017)

22 Immune Preclinical Research In ovarian cancer models in mice: Combination of gemcitabine and reovirus type 3 improved overall survival In melanoma models in mice: Combination of GM-CSF with REOLYSIN improved overall survival In brain cancer models in mice: Combination of a checkpoint inhibitor (anti-pd-1) with REOLYSIN improved overall survival 22

23 Enhancing Immune Responses to Improve Overall Survival Ongoing preclinical and clinical research has led to three clinical programs: 1. Gemcitabine in combination with REOLYSIN (REO 009 and REO 017); 2. GM-CSF in combination with REOLYSIN (Mayo (pediatric) and Leeds (adult)); or 3. Checkpoint inhibitors in combination with REOLYSIN (first study: pancreatic cancer, standard of care plus REOLYSIN plus pembrolizumab) 23

24 Registration Program for REOLYSIN Advanced Gliomas A key finding from REO 013 was that REOLYSIN can cross the blood brain barrier and subsequently infect and kill tumour in the brain, as well as primary gliomas and metastatic lesions from other primary cancers outside brain We have completed and initiated four studies of REOLYSIN in glioma patients: REO 003: Phase 12 local monotherapy REO 007: Phase 12 infusion monotherapy REO 013b: Phase 1 IV prior to surgical resection MC1472: Phase 1 IV combined with GM-CSF pediatric (ongoing) Second study assessing response in adult patients receiving REOLYSIN and the standard of care (surgery followed by radiation and temozolomide) Subject to confirmation of best approach proceed to pivotal trial, which will also measure overall survival 24

25 Manufacturing & Intellectual Property

26 Manufacturing Now produced at 100L (commercial scale) under cgmp with final formulation Commercial manufacturing agreement in place with Sigma- Aldrich Fine Chemicals (SAFC) 26

27 Patent Portfolio More than 400 patents issued worldwide, including 56 US and 20 Canadian Reovirus issue patent claims cover: o Compositions of matter comprising reovirus o Pharmaceutical use of reoviruses to treat neoplasia and cellular proliferative diseases o Combination therapy with radiation, chemotherapy and/or immune suppressants o Methods for manufacturing reovirus and screening for susceptibility to reovirus o Pharmaceutical use of reoviruses in transplantation procedures Approximately 235 pending applications worldwide 27

28 Oncolytic Virotherapy Summit December 3, 2015