ZYMEWORKS CORPORATE OVERVIEW

Transcription

1 ZYMEWORKS CORPORATE OVERVIEW

2 Legal Disclaimer This presentation includes forward-looking statements within the meaning of U.S. Private Securities Litigation Reform Act of 1995 and forward-looking information within the meaning of Canadian securities laws, or collectively, forward looking statements. Forward-looking statements include statements that may relate to our plans, objectives, goals, strategies, future events, future revenue or performance, capital expenditures, financing needs and other information that is not historical information. Forward-looking statements can often be identified by the use of terminology such as subject to, believe, anticipate, plan, expect, intend, estimate, project, may, will, should, would, could, can, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements, including, without limitation, our examination of historical operating trends, are based upon our current expectations and various assumptions. We may not realize our expectations, and our beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of risks and uncertainties, including those described in the "Risk Factors" and other sections of our public filings with the Securities and Exchange Commission and Canadian securities regulators. These forward-looking statements are made only as of the date hereof, and Zymeworks Inc. undertakes no obligation to update or revise the forward looking statements, whether as a result of new information, future events or otherwise, except as required by law. PAGE 2

3 Leading the Next Wave of Biotech Breakthroughs Corporate Extensive corporate assets Platforms Pipeline Partnerships Building a sustainable global business Platform licenses represent a source of non-dilutive capital Therapeutic Platforms Synergistic platforms to deliver multifunctional therapeutics Elegantly tailored solutions for complex biological challenges Validated by deals with 6 global pharma partners Comprehensive patent protection Pipeline Programs Proprietary lead program in the clinic Encouraging tolerability and anti-tumor activity in heavily pretreated breast and gastric cancers Deep and diverse wholly owned preclinical pipeline Second drug candidate poised to enter clinic PAGE 3

4 Industry-Leading Therapeutic Platforms Bispecific Antibodies Next-Gen Drug Conjugates Immune Function Modulation Multivalent Antibody- Alternatives 6 Active Partners PAGE 4

5 Strategic Partnerships and Collaborations Partners Events Programs Announced: 2011 Milestone #1: 2012 Multiple Milestone #2: 2013 Up to 3 Expanded: 2014 Announced: Expanded: Milestone #1: Milestone #2: Multiple Up to 5 (Includes Immuno-Oncology) Enabling Platform(s) Equity Azymetric TM EFECT TM - Azymetric TM C$27M (Initial) Royalty % Range Low-Mid Single Digit Low-Mid Single Digit Total Deal Size Announced: 2015 Multiple Up to 8 Azymetric TM C$10M (Initial) Low-Mid Single Digit 1.32B Announced: 2015 Multiple Up to 10 EFECT TM - Low Single Digit 1.10B Announced: 2016 Multiple Up to 6 Azymetric TM - Low-Mid Single Digit Announced: Milestone #1: One (Immuno-Oncology) Azymetric TM EFECT TM - Low Single Digit Announced: 2017 Multiple Up to 6 Option for 2 Additional Azymetric TM EFECT TM - Low-Mid Single Digit 1.45B (US$MM unless otherwise noted) Total: US $5.5 Billion PAGE 5

6 Synergistic Therapeutic Platforms Engineering fit-for-purpose biotherapeutics to maximize effect Azymetric Bispecifics Bispecific Fab Formats Hybrid Formats Alternate Formats EFECT Immune Modulation PAGE 6 ZymeLink AlbuCORE Drug Conjugates AntibodyAlternatives

7 Fully-Integrated Drug Development Engine Inhibition of Multiple Pathways Potent ADC Payloads Target Discovery, Selection and Antibody Generation Dual- Targeting of Receptors Complementary Therapeutic Platforms Azymetric EFECT ZymeLink AlbuCORE Biparatopic- Enhanced Payload Delivery Highly- Customized Fit-for-Purpose Therapeutics Finely-Tuned Immune Cell Engagement Antibody- Alternative Biologics Optimized PK Multivalent Targeting PAGE 7

8 Product Candidates and Discovery Programs Programs LEAD PRODUCT CANDIDATES Enabling Platform(s) Indication(s) DISCOVERY PRECLINICAL PHASE 1 PHASE 2 WORLDWIDE COMMERCIAL RIGHTS ZW25 HER2 x HER2 Bispecific ZW33 HER2 x HER2 Bispecific ADC Azymetric Azymetric Breast Cancer Gastric Cancer Breast Cancer Gastric Cancer PRECLINICAL AND ADVANCED DISCOVERY PROGRAMS Bispecific ADCs T Cell Engaging Bispecifics Checkpoint Modulating Bispecifics PARTNERSHIPS * Azymetric, EFECT ZymeLink Azymetric EFECT Azymetric EFECT Solid Tumors Solid Tumors Solid Tumors Bispecific Azymetric Immuno-Oncology Bispecific Azymetric, EFECT Not Disclosed Bispecific Azymetric Not Disclosed Bispecific Azymetric, EFECT Not Disclosed Bispecific Azymetric, EFECT Immuno-Oncology Bispecific Azymetric, EFECT Not Disclosed *Stage of most advanced publically disclosed program PAGE 8

9 Flexible Platforms to Drive Broader Therapeutic Applications Future Autoimmune Today Broader Oncology Inflammation Broader Oncology Underserved Oncology ZW25 & ZW33 Underserved Oncology Multiple Active Discovery Programs Underserved Oncology Future Discovery Programs Azymetric Azymetric EFECT ZymeLink AlbuCORE Azymetric EFECT ZymeLink AlbuCORE New Platforms PAGE 9

10 Key Value Drivers 2017 Highlights ü ZW25: Top-line data from the dose escalation portion of Phase 1 clinical trial ü ZW25: Safety and preliminary anti-tumor activity data at ASCO ü Lilly, Daiichi Sankyo, Merck announce progress of their Azymetric programs ü ZW25: Additional dose escalation data at ESMO ü Janssen Azymetric Partnership: ZW receives US$50M upfront payment, up to $1.45B deal value ü ZW25: Dose escalation and cohort expansion updates at SABCS 2018 Milestones q ZW25: Complete enrollment and report additional data from the adaptive Phase 1 clinical study q ZW25: Refine the regulatory strategy and accelerate development q File an Investigational New Drug (IND) Application for a wholly-owned product candidate q Present preclinical data showcasing maturing pipeline and evolving therapeutic platforms q Establish new strategic drug development partnerships PAGE 10

11 ZW25 Bispecific for HER2-Expressing Cancers Unique Mechanisms of Action Biparatopic - targets two distinct HER2 epitopes Increased binding density Potent effector-mediated cytotoxicity Blocks ligand-dependent and -independent tumor growth Enhanced HER2 down-regulation Clinical Data Highlights Clinical benefit 1 of single agent ZW25 observed in heavily pretreated HER2-High breast and gastric cancer patients Target lesions decrease in majority of patients 2 Best response in response-evaluable patients: Breast cancer: 5 PR; 2 SD; 4 PD Gastric cancer: 1 PR; 1 SD; 4 PD Partial Response, PR; Stable Disease, SD; Progressive Disease, PD 2018 Catalysts Complete enrollment and report additional data from the adaptive Phase 1 clinical study Refine the regulatory strategy and accelerate development 1 Confirmed PR or stable disease (SD) 6 months 2 14/19 patients with measurable disease per RECIST 1.1 criteria and at least one tumor re-staging PAGE 11

12 ZW25 Biparatopic HER2 Binding Drives Unique Mechanisms of Action ZW25 targets two distinct HER2 epitopes (biparatopic) leading to unique binding geometries Biparatopic Trans Binding Each HER2 receptor can be targeted by two ZW25 antibodies Monoclonal Binding Each HER2 receptor can only be bound by one monoclonal antibody Typical Monoclonal (Trastuzumab) Binding PAGE 12 ZW25 Biparatopic Trans Binding

13 ZW25 Biparatopic HER2 Binding Drives Unique Mechanisms of Action ZW25 s unique binding geometries promote: Extended chain formation and HER2 receptor clustering Enhanced HER2 internalization and downregulation Increased tumor cell binding density and potent effector function-mediated cytotoxicity Enhanced blockade of ligand-dependent and ligand-independent tumor growth Typical Monoclonal (Trastuzumab) Binding Trastuzumab PAGE 13 ZW25 Biparatopic Promotes Receptor Clustering ZW25

14 HER2 Classification for Breast Cancer HER2 Status HER2 High HER2 Intermediate HER2 Low HER2 Negative HER2 High 15.2% HER2 Assay Results IHC 3+, IHC 2+ or FISH Positive IHC 2+, FISH Equivocal or FISH Negative IHC 1+, FISH Equivocal or FISH Negative IHC 0 or FISH Negative HER2 Negative 18.5% HER2 Intermediate 25.9% Estimated Annual Incidence (US & EU5) 75, , ,159 92,115 HER2 Low 40.4% Potential Large Market Underserved for ZW25/ZW33 Population ZW25 and ZW33 - Expanding The Treatment Paradigm for HER2+ Cancer PAGE 14

15 ZW25 Adaptive Clinical Trial Design Part 1: 3+3 Dose Escalation & Schedule Exploration Weekly Schedule Bi-weekly Schedule Cohort 1 5 mg/kg IV QW Cohort 2 10 mg/kg IV QW Cohort 3 15 mg/kg IV QW Cohort 4 20 mg/kg IV Q2W Objectives Characterize safety and pharmacokinetics Evaluate potential anti-tumor activity per RECIST 1.1 every 8 weeks and potential biomarkers of response Selected Eligibility Requirements Locally-advanced (unresectable) or metastatic solid tumors that express HER2 Progression after standard of care therapies No known active brain metastases (stable treated brain metastases allowed) PAGE 15

16 ZW25 Single Agent Anti-Tumor Activity in HER2-High Breast and Gastric Cancer Patients Target Lesions Decrease in Majority of Patients with Measurable Disease 1 60 % Change in Target Lesions (SLD) * * * * -80 Patients HER2 Status 2 GE (1-003) GE (3-011) Breast (3-007) Breast (1-002) Breast (3-006) Breast (4-007) GE (3-002) GE (3-005) Breast (1-001) Breast (4-005) Breast (3-004) Breast (4-006) Breast (4-001) GE (3-010) na/fish+ 1+/FISH+ 2+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 3+/FISH+ 5 mg/kg, QW 10 mg/kg, QW 15 mg/kg, QW 20 mg/kg, Q2W 1 14/19 breast or gastric, gastroesophageal junction, or esophageal (GE) patients with measurable disease per RECIST 1.1 criteria and at least one tumor re-staging 2 HER2 status based on central assessment and refers to immunohistochemistry score / gene amplification status * PD due to new lesion Data as of November 16, 2017 (SABCS) PAGE 16

17 ZW25 Time on Study for HER2-High Breast and Gastric Cancer Patients Systemic Disease Control Observed Across All Dose Levels and Schedules PR PR cpr Breast Cancer PR PR PR cpr PD due to CNS lesion Gastric/GEJ Cancer PR cpr 6 months Days on Study 5 mg/kg, QW 10 mg/kg, QW 15 mg/kg, QW 20 mg/kg, Q2W missed dose PD, continued for clinical benefit Data as of November 16, 2017 (SABCS) PAGE 17

18 ZW25 Data Highlights and Timeline Actively Recruiting for Part 2: Single Agent Cohort Expansion Breast Cancer Summary Median 6 prior HER2-targeted regimens for metastatic disease 9 patients with measurable disease Disease control rate (best response of PR or SD): 64% (7/11): 5 PR, 2 SD, 4 PD 3 patients with PD due to CNS disease had systemic (non-cns) disease control (SD or PR) at time of progression Gastric Cancer Summary Median 4 prior treatment regimens 5 patients with measurable disease 6 of 8 patients evaluable for response Disease control rate (best response of PR or SD) 33% (2/6): 1 cpr, 1 SD, 4 PD Phase 1 Dose Escalation 5;10;15 mg/kg weekly 20 mg/kg bi-weekly Top- Line Data ASCO 2017 ESMO 2017 SABCS 2017 Single Agent Cohort Expansion Combination Tx Cohort Expansion Safety ZW25 was well-tolerated at all doses and schedules, with the most common adverse events being diarrhea, infusion reactions, or nausea, all Grade 1 or 2 in severity PAGE 18

19 ZW25 Phase 1 Dose Escalation Data Breast Cancer Best response : 5 PR, 2 SD, 4 PD (DCR = 64%) Median time on study 119 days (range: ) Median 6 prior HER2-targeted regimens for metastatic disease 3 Patients with PD due to CNS metastases had systemic disease control (SD or PR) at time of progression Patient Cohort HR Status Prior Approved HER2 Therapies # Prior HER2 Regimens (Metastatic Disease) Visceral Disease Known Prior Brain Metastases Best Response to ZW25 Time on Study (days) Status/Comments mg/kg QW - H, P, K 4 Yes No PR mg/kg QW - H, P, K, L 7 Yes No PD 63 Continued in SLD through C10; Off study due to PD end of C mg/kg QW + H, P, K, L 3 Yes No cpr 169 Off study due to PD end of C mg/kg QW - H, P, K, L 7 Yes Yes PR mg/kg QW + H, P, K, L 6 No No SD mg/kg QW + H, P, K 6 Yes Yes cpr mg/kg QW + H, K, L 6 No Yes PD 54 PD end of C4 due to LMD with continued systemic (non-cns) PR PD due to brain met in C3; continues on study with systemic SD Off study due to physician decision end of C6 (increased CEA) (C2: -8%, C4: -33%) mg/kg QW + H, K, L 5 Yes No PD 56 PD due to symptomatic brain mets mg/kg Q2W - H, P, K, L 8 Yes Yes PD mg/kg Q2W - H, P, K 5 Yes No PR 71 Off study due to physician decision C mg/kg Q2W - H, P, K 4 Yes No SD 119+ Active HR, Hormone receptor; H, trastuzumab; P, pertuzumab; K, T-DM1; L, lapatinib; LMD, leptomeningeal disease; SLD, sum of longest diameters; C, cycle Data as of November 16, 2017 (SABCS) PAGE 19

20 ZW25 Phase 1 Dose Escalation Data - Gastric Cancer 6 of 8 patients evaluable for response Best response: 1 cpr, 1 SD, 3 PD (DCR = 33%) Patient with cpr experienced a 71% decrease in their target lesions Patient with SD on study > 6 months Median 4 prior systemic regimens Patient Cohort HER2 Status (per Central review) Prior Approved HER2 Therapies Prior Systemic Regimens Any, n Best Response to ZW25 Time on Study (days) Status/Comments mg/kg QW NA H 4 PD 55 FISH+ per local assessment; Biopsy unavailable for central review mg/kg QW 3+, FISH+ H 2 SD % in SLD end of C6; PD end of C mg/kg QW 1+, FISH- H 3 PD mg/kg QW 3+, FISH+ H 6 PD mg/kg Q2W 3+, FISH+ H 3 cpr 115+ PD due to new lesion end of C2 with 24% in target lesions cpr with 71% in SLD end of C4, still active mg/kg Q2W 1+, FISH+ H, K 7 PD 57 1 IHC1+/FISH- based on central assessment, but previously treated as IHC 3+/FISH+ based on original local review. Two patients were not evaluable for response. One patient withdrew consent and one patient left study due to a small bowel obstruction deemed unrelated to study drug. DCR, % of evaluable patients with best response of either CR, PR or SD at any time. Data as of November 16, 2017 (SABCS) PAGE 20

21 Key Value Drivers 2017 Highlights ü ZW25: Top-line data from the dose escalation portion of Phase 1 clinical trial ü ZW25: Safety and preliminary anti-tumor activity data at ASCO ü Lilly, Daiichi Sankyo, Merck announce progress of their Azymetric programs ü ZW25: Additional dose escalation data at ESMO ü Janssen Azymetric Partnership: ZW receives US$50M upfront payment, up to $1.45B deal value ü ZW25: Dose escalation and cohort expansion updates at SABCS 2018 Milestones q ZW25: Complete enrollment and report additional data from the adaptive Phase 1 clinical study q ZW25: Refine the regulatory strategy and accelerate development q File an Investigational New Drug (IND) Application for a wholly-owned product candidate q Present preclinical data showcasing maturing pipeline and evolving therapeutic platforms q Establish new strategic drug development partnerships PAGE 21

22 Management Team Ali Tehrani, Ph.D. President & Chief Executive Officer Diana Hausman, M.D. Chief Medical Officer Neil Klompas, CPA, CA Chief Financial Officer John Babcook SVP, Discovery Research Surjit Dixit, Ph.D. VP, Platform Technologies Wajida Leclerc VP, Human Resources Founded Zymeworks in Current Board member of LifeSciences BC, Creatus Biosciences Inc., CQDM and a member of the BC Premier s Tech Council. Past member of the MITACS and BIOTECanada Advisory Boards and Committees. PhD (Microbiology & Immunology) from UBC, MSc (Biochemistry) from UMass Over fifteen years of clinical drug development experience. Former CMO at Oncothyreon and previously at ZymoGenetics, Berlex and Immunex. Internal medicine and specialty training at U of WA, MD from University of Pennsylvania and AB (Biology) from Princeton Chartered Professional Accountant with over 20 years of healthcare and biotech experience. Formerly with KPMG s U.S. Biotech/Pharma M&A Transaction Advisory Group and Canadian Life Sciences practices Former President and CSO of Kairos Therapeutics, with over 20 years of biologics research. Co-founder of ImmGenics Pharmaceuticals and he has participated in the development of more than 100 therapeutic antibody-based programs Former coordinator for Computational Molecular Biophysics, Weselyan University. PhD and MSc (Chemistry) from Indian Institute of Technology (New Delhi). He leads the implementation and advancement of our proprietary ZymeCAD approach Prior to Zymeworks, Ms. Leclerc was the Senior Director, Human Resources at QLT Inc. and Xenon Pharmaceuticals. BA (Liberal Arts and Business) from SFU Jennifer Kauffman-Shaw, Ph.D., LLB VP, Intellectual Property & Legal Affairs Over 20 years in global intellectual property strategy and management. Formerly part of the senior management teams at QLT Inc. and Sirius Genomics and co-founder of ImStar Therapeutics. PhD and LLB from U of A. PAGE 22

23 Board of Directors Nick Bedford Chairman Kenneth J. Hillan, M.B., Ch.B. Hollings Renton, MBA Natalie Sacks, M.D. Ali Tehrani, Ph.D. Lota S. Zoth, CPA Independent consultant. Former Chairman of the Board of ActiveState Corp. and Head of German Equities at UBS Chief Executive Officer of Achaogen and a member of its Board of Directors since October 2011 Independent consultant. Former Chairman, CEO and President of Onyx Pharmaceuticals, and current member of the board of directors of AnaptysBio and Portola Pharmaceuticals Chief Medical Officer of Aduro Biotech and previously VP of Clinical Development at Onyx Pharmaceuticals Founded Zymeworks in Current Board member of LifeSciences BC, Creatus Biosciences Inc., CQDM and a member of the BC Premier s Tech Council. Past member of the MITACS and BIOTECanada Advisory Boards and Committees. PhD (Microbiology & Immunology) from UBC, MSc (Biochemistry) from Umass Independent consultant. Former Chief Financial Officer of MedImmune Inc. PAGE 23

24 ZYMEWORKS CORPORATE OVERVIEW