Leading the Next Wave of Biotech Breakthroughs

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1 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 clinic Anti-tumor activity in heavily pretreated gastric, breast and other HER2-expressing cancers Deep and diverse wholly owned preclinical pipeline Second drug candidate poised to enter clinic PAGE 1

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 Industry-Leading Therapeutic Platforms Bispecific Antibodies 6 Active Partners PAGE 3 Next-Gen Drug Conjugates Immune Function Modulation Multivalent AntibodyAlternatives

4 ZW25 Biparatopic HER2 Binding Drives Unique Mechanisms of Action HER2 ECD2 HER2 ECD4 ZW25 PAGE 4

5 ZW25 Biparatopic HER2 Binding Drives Unique Mechanisms of Action Increased Tumor Cell Binding HER2 Receptor Clustering Enhanced Internalization MFI Internalization 37 C, 24h ZW25 Trastuzumab 2000 MFI MFI Concentration (nm) ZW25 Trastuzumab Single ZW25 Antibody ZW25-HER2 Cluster MCF7 JIMT-1 SKOV3 BT-474 MCF7 JIMT-1 SKOV3 BT-474 HER2 IHC (0/1+) (2+) (2/3+) (3+) JIMT-1 (HER2 2+) Transmission Electron Microscopy Internalization 37 o C, 24h PAGE 5

6 ZW25 Bispecific for HER2-Expressing Cancers HER2 HER2 Unique Mechanisms of Action Biparatopic - targets two distinct HER2 epitopes Increased tumor cell binding Potent effector-mediated cytotoxicity Blocks ligand-dependent and -independent tumor growth Enhanced HER2 internalization and down-regulation Clinical Data Highlights Clinical benefit 1 of single agent ZW25 observed in heavily pretreated breast and gastric cancer patients Target lesions decrease in majority of patients 2 Best response in response-evaluable patients: 12 Partial Response; 6 Stable Disease; 15 PD 2018 Catalysts Report additional data from Monotherapy and Combination Cohort Expansion phases Complete single agent enrollment Refine regulatory strategy and accelerate development 1 Confirmed partial response or stable disease 6 months 2 21/31 patients with measurable disease per RECIST 1.1 criteria and at least one tumor re-staging PD; progressive disease PAGE 6

7 ZW25 Adaptive Clinical Trial Design Weekly and every two week dosing regimens evaluated Recommended dose and schedule: 10 mg/kg weekly or 20 mg/kg every two weeks 3+3 Dose Escalation (n=22) RD Expansion Cohorts (n=20) 1 Weekly ZW25 IV Days 1, 8, 15, and 22 of 28 day cycle 5 mg/kg IV QW (n=3) 10 mg/kg IV QW (n=6) No DLTs HER2 High breast cancer (n=9) HER2 High and Intermediate Gastroesophageal (n=5) Every 2 Weeks 15 mg/kg IV QW (n=7) HER2 High other cancers (n=6) ZW25 IV Days 1 and 15 of 28 day cycle 20 mg/kg IV Q2W (n=6) 1 Enrollment ongoing. Data as of cut-off date of 18 April 2018 PAGE 7

8 ZW25 Safety Overview Well-tolerated with no dose-limiting toxicities Treatment-related AEs all Grade 1 or 2 except in one patient Reversible Grade 3 hypophosphatemia, arthralgia and fatigue (10 mg/kg QW) No treatment-related serious adverse events or discontinuations No LVEF decreases 10% during treatment No new detectable anti-drug antibodies PAGE 8

9 ZW25 Single Agent Anti-Tumor Activity in HER2-Expressing Cancer Patients Target Lesions Decrease in Majority of Patients with Measurable Disease 1 % Change in SLD at Best Response Breast Gastroesophageal Colorectal Cervical Salivary gland Gallbladder -90 SLD = sum of longest diameters 1 11/42 patients not evaluable for change in SLD: too early (n=3); no target lesions (n=4); CNS progression on Day 14 (n=1); clinical progression on Day 21 (n=1); withdrawal of consent (n=1); unrelated SAE (n=1). PAGE 9

10 Breast Cancer: Single Agent Anti-tumor Activity All 20 patients with history of HER2 High breast cancer, and median 5 prior HER2-targeted regimens for metastatic disease Prior trastuzumab (T) = 100%; T-DM1 (K) = 95%; pertuzumab (P) = 85%; lapatinib (L) = 50%; investigational agent (I) = 35% % Change in SLD at Best Response * # # # # 5 mg/kg QW 10 mg/kg QW 15 mg/kg QW 20 mg/kg Q2W TPKI TKL TPKI TKL TPK 1 TP TPKLI TKL TPKL TPKI TPK TPKL TPK TPKLI TPK TPKl TPKL * * PD due to new CNS lesion # PD due to new lesion 1 HER2 negative liver biopsy obtained at study entry; progressive disease in liver SLD = sum of longest diameters. 3/20 breast cancer patients not evaluable for change in SLD: no measurable disease (n=2); clinical progression on Day 21 (n=1). PAGE 10

11 Gastric Cancer: Single Agent Anti-tumor Activity Median 4 prior systemic regimens, including prior trastuzumab in all patients % Change in SLD at Best Response # HER2 Status HIGH HIGH 1 HIGH HIGH INT HIGH HIGH HIGH 5 mg/kg QW 10 mg/kg QW 15 mg/kg QW 20 mg/kg Q2W HER2 High: IHC 3+ or 2+/FISH+; HER2 Intermediate: IHC 2+/FISH-; HER2 Low: IHC 1+/FISH-; HER2 Negative: IHC 0/FISH- # PD due to new lesion 1 IHC1+/FISH+; 5/13 patients GEA patients not evaluable for change in SLD: too early (n=1); no measurable disease (n=1); CNS PD Day 14 due to brain metastases (n=1); unrelated SAE (n=1); and withdrawal of consent (n=1). PAGE 11

12 Other HER2 High Cancers: Single Agent Anti-tumor Activity All patients with history of HER2 High cancer Median 4 prior systemic regimens % Change in SLD Change in Target Lesions at Time of Best Response # 10 mg/kg QW 15 mg/kg QW 20 mg/kg Q2W Colorectal Cervical Colorectal Salivary Colorectal Gallbladder # PD due to new lesion HER2 heterogeneous (HER2 High/HER2 Negative by central review) Colorectal Colorectal TP Salivary Gallbladder T Colorectal TP Cervical T Adnexal TPK Colorectal Colorectal TKLI Time on Treatment SD SD SD PR # PR Active Patients Days on Treatment 3/9 patients not evaluable for change in SLD: too early (n=2); no measurable disease (n=1). T = trastuzumab; P = pertuzumab; K = T-DM1; L = lapatinib; I = investigational agent PAGE 12

13 ZW25 Summary Well tolerated at all dose levels/schedules in heavily pretreated patients Recommended dose 20 mg/kg every two weeks Cytotoxin-free anti-tumor activity across multiple cancers HER2 High breast cancer with median 5 prior HER2-targeted regimens HER2 High and HER2 Intermediate gastroesophageal cancers after prior tras HER2 High colorectal, gall bladder and salivary gland cancers Validates Azymetric platform and biparatopic approach to overcome target resistance PAGE 13

14 ZW25 Ongoing Activities Continuing evaluation as single agent Late stage HER2 High gastroesophageal cancers HER2 High colorectal and other cancers Evaluating combinations with other agents in earlier lines of therapy Gastroesophageal and breast cancers Expanding early dataset in lower HER2-expressing cancers PAGE 14

15 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 ZW49 HER2 x HER2 Bispecific ADC Azymetric Azymetric ZymeLink Breast, Gastric, & Other HER2-Expressing Cancers HER2-Expressing Cancers 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 publicly disclosed program PAGE 15

16 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 clinic Anti-tumor activity in heavily pretreated gastric, breast and other HER2-expressing cancers Deep and diverse wholly owned preclinical pipeline Second drug candidate poised to enter clinic PAGE 16

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