HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY

Transcription

1 HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY Leslie Chong Managing Director & Chief Executie Officer October 2018 Deeloping Cancer Immunotherapies

2 Notice: Forward Looking Statements Any forward looking statements in this presentation hae been prepared on the basis of a number of assumptions which may proe incorrect and the current intentions, plans, expectations and beliefs about future eents are subject to risks, uncertainties and other factors, many of which are outside Imugene Limited s control. Important factors that could cause actual results to differ materially from any assumptions or expectations expressed or implied in this brochure include known and unknown risks. As actual results may differ materially to any assumptions made in this brochure, you are urged to iew any forward looking statements contained in this brochure with caution. This presentation should not be relied on as a recommendation or forecast by Imugene Limited, and should not be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction in which it would be a contraention of applicable law. 2

3 EXECUTIVE SUMMARY Experienced Management & Board Meeting milestones Successful M&A actiity Imugene B-cell Vaccine Pipeline Broadened and strengthened clinical programs globally, including U.S. and European centres HER-Vaxx milestones of Phase 1b recruitment completed; Phase 2 actiity commenced B-Vaxx Phase 2 ongoing KEY-Vaxx pre-clinical work started Synergistic Technology Licensed from Ohio State Uniersity and The Mayo Clinic Full spectrum of indications and targets to choose from, including checkpoint inhibitors and combination therapies 3

4 A TEAM WITH A TRACK RECORD IN DRUG DEVELOPMENT Leslie Chong (Sydney, Australia) Managing Director & Chief Executie Officer Oer 20 years of oncology experience in Phase I III of clinical program deelopment Leadership role inolement in two marketed oncology products Preiously Senior Clinical Program Lead at Genentech, Inc., in San Francisco Paul Hopper (Sydney, Australia) Executie Chairman International & ASX biotech capital markets experience particularly in immuno-oncology & accines Former Chairman of Viralytics, Founder & Director of Prescient, Founder of Imugene & Polynoma LLC, former Director psiida, Somnomed & Fibrocell Science Dr Axel Hoos (Philadelphia, U.S.A.) Non-Executie Director Senior Vice President and Head of Oncology at GSK Former Medical Lead for Yeroy, the first surial improing medicine in Immuno-Oncology Chairman of the BoD of the Sabin Vaccine Institute Co-Chair of the Cancer Immunotherapy Consortium Think-Tank Mr. Charles Walker (Brisbane, Australia) Non-Executie Director Experienced listed biotech CEO and CFO (ASX;ACL and ASX:IMU) Experienced in financial markets including executing 55 international tech corporate transactions Clinical experience includes managing pipeline of drugs in all stages form discoery, through to Phase III to launched products Dr Mark Marino (California, U.S.A.) Chief Medical Officer Oer 28 years of experience in drug deelopment Former CMO of Cytori, Head of Clinical Pharmacology at Eisai and Roche, Head of Research and Early Deelopment at Mannkind, VP Clinical Deelopment at Daiichi Dr Nick Ede (Melbourne, Australia) Chief Technology Officer Oer 25 years peptide accine and drug deelopment Former CEO Adistem, CEO Mimotopes VP Chemistry Chiron (now Noartis), Research Fellow CRC Vaccine Technology Dr Anthony Good (Sydney, Australia) Vice President of Clinical Research Oer 20 years global clinical deelopment experience. Integral to the deelopment of significant new medicines including Viagra, Reatio, Lipitor, and Somaert. Ex Pfizer Global Research and Deelopment, Ex Coance Clinical Serices. 4

5 IMUGENE SCIENTIFIC ADVISORY BOARD Prof Prain Kaumaya Ohio State Uniersity, U.S.A. Prof of Medicine Department of Obstetric Gynecology at Ohio State Uniersity Research focus in tumour immunology, mechanisms of tumour cell-immune cell interactions, and immune mechanisms Research focus on fields of accine with emphasis on peptide accines for cancer Prof Peter Schmid Barts Cancer Institute, Queen Mary Uniersity of London Prof. Ursula Wiedermann-Schmidt Medical Uniersity of Vienna, Austria Co-inentor of HER-Vaxx Professor of Vaccinology at Medical Uniersity of Vienna Medical Oncologist Expertise in breast and lung cancer, cancer immunotherapy and early drug deelopment Leads the Centre of Experimental Medicine at Barts Cancer Institute Dr Neil Segal Memorial Sloan Kettering Cancer Center, U.S.A. Medical Oncologist Expertise in GI, Colon, Pancreatic cancers Actie clinical immuno-oncology researcher Clinical lead in seeral trials using PD-L1 inhibitors Prof Tanios BekaiI Saab Mayo Clinic, U.S.A. Professor of College of Medicine and Science Program Co-Leader, GI Cancer, Mayo Clinic Cancer Center Medical Director, Cancer Clinical Research Office (CCRO) Senior Associate Consultant, Mayo Clinic AZ Prof. Josep Tabernero Vall d Hebron, Barcelona, Spain President of European Society for Medical Oncology (ESMO) President of the Medical Oncology Department at the Vall d Hebron Director of the Vall d Hebron Institute of Oncology (VHIO) Dr Yelina Janjigian Memorial Sloan Kettering Cancer Center, U.S.A. Medical Oncologist Expertise in esophageal and stomach (gastric) cancer Actie in GI clinical trials testing combinations of Her-2 and checkpoint inhibitor therapies 5

6 Imugene deelops accines to boost and direct the body s immune system to specifically target and attack cancer cells. 6

7 A BETTER WAY TO MAKE ANTIBODIES TO TREAT CANCER? In a facility: Using B-cells in your body VS B-cells are cells in the human body that naturally produce millions of antibodies For example, Merck s PD-1 inhibitor Keytruda Teaching B-cells to make antibodies using peptide antigens 7

8 HER-Vaxx MIMOTOPE: MECHANISM OF ACTION Peptides mimic the epitope HER-Vaxx Antibody Secretion Tumor Cell 3 Peptides B-cell Actiation Via helper T- cells HER-2/neu EPITOPE = Antibody Binding Site HER-Vaxx Immunotherapy B-Cell HER-Vaxx attacks the same target as the the world s largest selling breast cancer drug Herceptin 8

9 CURRENT PHASE 1B/2, IN GASTRIC CANCER Phase 1b Lead-in Phase 2 Open label ~Up to 18 patients in 3 cohorts of up to 6 pts per cohort Combination with chemo/cisplatin Endpoints: - Recommended Phase 2 Dose of HER-Vaxx - Safety: any HER-Vaxx toxicity - Immunogenicity (anti-her-2 antibody titres) Open label ~70 patients from sites in Asia Combination with chemo Randomized Primary Endpoints: - TBD PFS and/or OS - (cont. on Ph1b results) Secondary endpoint: - Immune response 2H, 2017 : Phase 1B Patients Enrolled 2H, 2018: Phase 1B Recruitment Completed 1H, 2019: Commence Phase 2 1H, 2020: Interim Phase 2 Data Aailable 9

10 STRATEGIC AQUISITION WORLDWIDE EXCLUSIVE LICENSE Six patent families, 22 patents IND ready PD-1 clinical trial (Phase 1) Ongoing Her-2 clinical trial (Phase 2) Six additional clinical candidates Her-1, Her-2, Her-3, VEGF, IGF-1R CD28 Three year R&D contract with access to Ohio translational labs Access to experience and expertise with Prof. Prain Kaumaya and team 10

11 PROF PRAVIN KAUMAYA & DR TANIOS BEKAII SAAB For reprint orders, please contact: Could precision-engineered peptide epitopes/accines be the key to a cancer cure? Combination cancer accines with peptide mimics hae the potential to treat existing cancer and preent its recurrence. Prain TP Kaumaya The Ohio State Uniersity, Department of Obstetrics & Gynecology, Suite 316 Medical Research Facility, 420 W. 12th Ae., Columbus, OH 43210, USA kaumaya.1@osu.edu 11

12 IMUGENE PIPELINE CLINIC OR CLINIC READY PROGRAM PRE-CLINICAL PHASE 1 CLINICAL DEVELOPMENT PHASE 2 HER-Vaxx (HER2) B-Vaxx (HER2) KEY-Vaxx (PD-1) Her-2 & PD-1 Combo DISCOVERY PIPELINE PROGRAM DISCOVERY/PRE-CLINICAL ID OF CANDIDATE Combination: Her-1; Her-2; Her-3; IGF-1R Her-1 (EGFR) Her-3 IGF-1R VEGF Combination (numerous) PD-1/PDL-1 12

13 ACQUIRED HER-2 VACCINE (B-Vaxx): ENCOURAGING PHASE 1 TRIAL RESULTS 10 out of 24 patients had stable disease & 1 out of 24 patients had partial response; 1 patient had PFS at 40+ months No toxicity obsered % maximal change in SPD from baseline 160% 140% 120% 100% 80% 60% 40% 20% 0% -20% -40% -60% -80% * * dose leel 1 dose leel 2 dose leel 3 dose leel 4 Best Response PR * SD PD if not indicated * * * * * Phase Ib Immunotherapy Trial with a Combination of Two Chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B Cell Peptide Vaccine emulsified in ISA 720 and nor-mdp Adjuant in Patients with Adanced Solid Tumors, Immunological Response and Clinical Outcome. Tanios Bekaii-Saab, Daniel H. Ahn, Christina Wu, Robert Wesolowski, Amir Mortazai, Maryam Lustberg, Jeffrey Fowler, Bhuaneswari Ramaswamy, Lai Wei, Jay Oerholser and Prain T.P. Kaumaya. Cancer Discoery2018 manuscript in preparation 13

14 WHY SELECT AND TARGET PD-1 FOR B-CELL VACCINATION? Monoclonal antibody immunotherapies Keytruda (Merck) and Opdio (BMS) targeting PD-1 sold USD$3.8B and $4.9B, respectiely, in In industry-recognized mouse cancer models (colon cancer), the PD-1 targeting B-cell accine is more superior than the gold standard mouse PD-1 monoclonal antibody (used in preclinical model testing for Keytruda and Opdio). Whilst acknowledging the rapid rise in clinical trials inoling PD-1 and their combination with other treatments *, a PD-1 B-cell accination approach represents a paradigm shift in cancer immunotherapy. * Tang etal. Comprehensie analysis of the clinical immuno-oncology landscape, Annals of Oncology, The combination of the PD-1 accine with the acquired Phase II Her-2 accine significantly inhibits tumor growth c/w mab control in a Her-2+ model of colon cancer. 14

15 PD-1/HER-2 VACCINE COMBINATION ACTIVE IN MODEL OF COLORECTAL CANCER WITH NO SIGNS OF TOXICITY All mice accinated oer a period of 9 weeks showed no signs of scruffiness, lesions, and lethargy Organs (spleen, lier, heart, lung, kidney, and tumor) from the Balb/c mice accinated with combination peptides (HER-2 and PD-1) were collected from mice and submitted for analysis % Cancer growth inhibition in Colorectal cancer model PD-1 accine plus Her-2 accine PD-1 accine 65% 90% No significant lesions were noted in any of the organs submitted for histologic ealuation. PD-1 mab 39% There were also no oert biochemical abnormalities noted. Control (PBS) 0% 0% 20% 40% 60% 80% 100% Inhibition of cancer growth 16 days after infusion of cancer cells 15

16 PD-1 KEY-VAXX VACCINE PHASE 1 DEVELOPMENT PATH PD-1 candidate accine Identified May, 2018 CMC manufacturing Formal pre-clinical Finalise regulatory IND submissions 2019: Commence Phase 1 Proposed Adaptie Phase 1/2 PD-1 Vaccine Design Expansions Assumption Dose Finding Signal Seeking Cohort 1 Cohort Cohort OBD *Safety *Immunogenecity *Tumor PD Expansion Indication Expansion (12-20 patients) Indication Expansion (12-20 patients) Proof of Concept 16

17 FINANCIAL SUMMARY ASX:IMU Options on issue (as at July 2018) Market Cap (31/Jul/18): Ordinary Shares: $79.2M AUD, $58.9M USD billion Listed: (IMUOA) Listed: (IMUOB) No. of options Exercise Price Expiry 242.5M $ /11/ M $ /11/2021 Unlisted: 79.5M $0.024* 09/03/2020* 12 month price range: 1.3 cents 3.9 cents AUD Ag daily olume: 9.5M shares (April-July 2018) Total: 570.3M $0.03* 01/07/2020* Top 5 shareholders (as at July 2018) No. of Shares % Capital * Aerage Inestment to Date: Cash & Equialents: ~$42.5M (public) ~$ 5.5M (VC) $25.8M (as at 31 July 2018) Priate Portfolio Management 240,906, % Platinum Asset Management 165,986, % Dr. Nicholas Smith 86,000, % J P Morgan Nominees Australia Limited 79,957, % Paul Hopper Executie Chairman 75,678, % 17

18 EXECUTIVE SUMMARY Experienced Management & Board Meeting milestones Successful M&A actiity Imugene B-cell Vaccine Pipeline Broadened and strengthened clinical programs globally, including U.S. and European centres HER-Vaxx milestones of Phase 1b recruitment completed; Phase 2 actiity commenced B-Vaxx Phase 2 ongoing KEY-Vaxx pre-clinical work started Synergistic Technology Licensed from Ohio State Uniersity and The Mayo Clinic Full spectrum of indications and targets to choose from, including checkpoint inhibitors and combination therapies 18

19 EXECUTIVE SUMMARY Experienced management & board: Meeting milestones and successful M&A actiity Imugene B-cell accine pipeline: Broadened and strengthened clinical programs globally, include U.S. and European centres HER-Vaxx milestones of Phase 1b recruitment completed; Phase 2 actiity commenced B-Vaxx Phase 2 ongoing KEY-Vaxx pre-clinical work started Synergistic technology licensed from Ohio State Uniersity and The Mayo Clinic: Full spectrum of indications and targets to choose from, including check point inhibitors and combination therapies 19

20 Leslie Chong Chief Executie Officer & Managing Director