Slide 1: Making a Meaningful Difference
Making a Meaningful Difference Accelerating the next generation of therapeutics to improve the standard of care for the most challenging diseases in cancer, autoimmune and inflammatory disease June 2025 Nasdaq: ZYME | zymeworks.com
Slide 2: Legal Disclaimer
Legal Disclaimer This presentation and any accompanying oral commentary include “forward-looking statements” or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of
Slide 3: Zymeworks: Global Biotech Focused on Targeted Therapies
Zymeworks: Global Biotech Focused on Targeted Therapies Starting with Patients Driven by Science & Empowered by People • Focusing on challenging, Technology • Robust leadership team with multi-factorial diseases with • Suite of ADC technologies decades of experience in drug significant unmet medical
Slide 4: Differentiated Pipeline of Multifunctional Therapeutics
Differentiated Pipeline of Multifunctional Therapeutics Program Technology Target Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Solid Tumor Oncology: Antibody-Drug Conjugates (ADC) ZW191 Gynecological Topo1i ADC | DAR 8 | Fc WT ZD06519 Payload FRα Thoracic NCT06555744 ZW220 Gynecological
Slide 5: 10+ Years of Pioneering Multifunctional Antibody Development
10+ Years of Pioneering Multifunctional Antibody Development Leading the development of next generation antibody-drug conjugates ZW220 & ZW251 Novel Payload Zymelink PreCysion nominations Mechanisms & Hemiasterlin Site- Specific Targeting Moieties & Auristatin Conjugation TOPO1i Platform ZW191 2010
Slide 6: Recent Accomplishments and Near-Term, Upcoming Milestones
Recent Accomplishments and Near-Term, Upcoming Milestones 5+ Strategic Partnerships 1 Internally Developed FDA Approved Drug 6 Nominated Wholly-Owned Candidates Collaborating with industry Ziihera® (zanidatamab-hrii) Multiple Modalities and leaders to accelerate impact (HER2 bispecific antibody) The
Slide 7: Strategic Priorities for 2025 and 2026
Strategic Priorities for 2025 and 2026 Build a diverse and Become a leading, global Invest in our people, differentiated pipeline biotech focused on culture & society targeted therapies Expand solid tumor portfolio with an Harness global presence rooted in emphasis on digestive system cancers R&D to
Slide 8: Focused Therapeutic Areas Provide Diversity to R&D Portfolio
Focused Therapeutic Areas Provide Diversity to R&D Portfolio and Enhanced Optionality for Partnering and Retained Product Rights Solid Tumors Hematological Cancers Autoimmune & • Gynecological cancers • AML Inflammatory Disease • Thoracic cancers • Multiple myeloma • Respiratory diseases • Digestive
Slide 9: Zanidatamab: $2B+ Peak Sales Potential
Zanidatamab: $2B+ Peak Sales Potential* The approval of Ziihera® is the result of over a decade of groundbreaking research and development at Zymeworks 01 Entering market first in BTC with U.S. FDA Approval 02 Path to approval in 1L GEA with sBLA with top-line results estimated 2H 2025 Strong Track
Slide 10: Azymetric: Adaptable to Different Formats and Applications
Azymetric™: Adaptable to Different Formats and Applications Engineering Set of transferable mutations supporting pure and stable Fc heterodimer Simultaneous formation with exclusive chain pairing during Pathway 1 + 1 Formats co-expression Blockade Bispecific Libraries of constant domain Fab mutation
Slide 11: Advancing Our Next-Generation Technology in Challenging Diseases
Advancing Our Next-Generation Technology in Challenging Diseases Antibody-Drug Conjugates Multispecific Antibody Therapeutics Novel Payload Discovery Advanced Protein Engineering Solutions • Our hypothesis on ADC mechanism guides our approach to novel • FDA approved, clinically validated, and novel
Slide 12: Zymeworks Topoisomerase ADC Platform Exemplifies Our Philosophy
Zymeworks Topoisomerase ADC Platform Exemplifies Antibody-Drug Conjugates Our Philosophy and Enables Our Pipeline Payload synthesis ADC in vitro Moderate potency to enable & screening potency higher ADC dose ~100 payloads prepared In vitro potency: and tested in vitro target-dependency and bystander
Slide 13: Zymeworks' Engineering Approach: Format and Geometry Screening
Multispecific Antibody Therapeutics Zymeworks’ Engineering Approach: Key Expertise in Format and Geometry Screening to Identify Differentiated Activity Biparatopic Multi-Cytokine Blocker Zanidatamab ZW1528 (IL4Rα x IL33) Optimization of affinity and format IgG-like format, manufacturability and PK f
Slide 14: Maintain Focus on Cancers with Highest Unmet Medical Need
Maintain Focus on Cancers with Highest Unmet Medical Need: Increase GI Tract and Thoracic Cancer Coverage and Expand to Heme-Onc Cancers Therapeutic focus areas | ZYME Development Programs 100 Testis Thyroid Melanoma Prostate HR+ HER2+ BC HR+ HER2- BC HL CLL Endometrial (ZW91, ZW171, ZW220) 80 HR- H
Slide 15: Target Selection Driven by Expression Profile, Biology and Clinical Precedence
Target Selection Driven by Expression Profile, Biology and Clinical Precedence Selection of an ADC or TCE strategy is driven by target expression, biology including internalization rate, clinical precedence and differentiation to prior therapeutic programs mRNA Expression Profile of Select Cancer Ta
Slide 16: ZW171: Bispecific Antibody Designed to Target MSLN Cancers
Optimized Design1 • T cell-engaging bispecific antibody for the treatment of MSLN- expressing solid tumors, built with Azymetric™. • Unique geometry: Two single-chain fragment variable arms targeting MSLN; one Fab arm targeting the CD3 component of the T cell receptor, redirecting the body’s immune
Slide 17: ZW171: Mesothelin Expression Is Frequent in Ovarian Cancer
ZW171: Mesothelin Expression Is Frequent Proportion of Patients with MSLN+ Tumors (%) in Ovarian Cancer, Endometrial Cancer, NSCLC, PDAC, and 5.1% Other Malignancies 8.4% 12.0% IHC 11.1% 4.4% 21.9% Strong 19.0% 17.4% 3+ 83.8% 10.1% 13.8% 2+ 53.0% Mod 40.6% 29.0% 22.4% 1+ Weak TPS NSCLC Adeno Endomet
Slide 18: ZW171 Exhibits a Wider Therapeutic Window Compared to Next Gen MSLN TCEs
ZW171 Exhibits a Wider Therapeutic Window Compared to Next Gen MSLN TCEs Enhanced tumor selective cytotoxicity ZW171 CT951 JNJ-790324212 AMG 3053 (LNK101) No targeting of normal tissues Low affinity CD3 binding to mitigate peripheral T cell binding and cytokine release Maintains potency in the prese
Slide 19: ZW171: Mediates Strong Anti-Tumor Activity in Patient-derived Models
ZW171: Mediates Strong Anti-Tumor Activity in Patient-derived Models Patient-derived NSCLC Humanized Patient-derived Pancreatic Cancer Ovarian Cancer Model Leveraging Mouse Model Humanized Mouse Model Endogenous Tumor T cells NSCLC (CTG-2579) donor 2 PDAC (CTG-1375) Negative 1500 control 1500 10000
Slide 20: ZW171 Global Phase 1 Study in MSLN-Expressing Solid Tumors
ZW171 Global Phase 1 Study in MSLN-Expressing Solid Tumors (NCT06523803) Open-label, FIH, dose-escalation study USA USA Part 1: Dose Escalation N= ~160 Part 2: Dose Optimization and Expansion Dose Optimization Dose Expansion United Kingdom Advanced UK ovarian, NSCLC malignancies MTD/RD Cohort 2: NSC
Slide 21: ZW191: ADC Designed to Target FRα-Expressing Tumors
Optimized Design1 • ADC targeting FRα -expressing tumors including ovarian cancer, other gynecological cancers, and NSCLC. • Comprised of a humanized IgG1 antibody conjugated to a novel camptothecin-based topoisomerase 1 inhibitor payload technology, ZD06519. • Drug-to-antibody ratio ~8. • Validated
Slide 22: FRα-expressing Cancers Represent a Significant Commercial Opportunity
FRα-expressing Cancers Represent a Significant Commercial Opportunity1-7 Potential first and best-in-class in Potential best-in-class opportunity in FRα-high endometrial, NSCLC, TNBC, and FRα-mid/low solid FRα-high ovarian cancer tumors FRa-Expressing Cancers Estimate of Newly Diagnosed FRα+ Patient
Slide 23: ZW191: Key Design Considerations
ZW191: Key Design Considerations ZW191’s Novel mAb Drives Superior Internalization, Anti-tumor Activity Across Multiple Tumor Types And Payload Delivery, and Tissue Penetration Range of FRα Expression (PDX models) IGROV-1 KB-HeLa Intracellular Payload Ovarian Cancer Internalization Cervical Carcinom
Slide 24: Differentiation is Critical for ZW191 in the Competitive FRα ADC Space
Differentiation is Critical for ZW191 in the Competitive FRα ADC Space for TOPO1i A novel design to target FRα The balance between drug-linker stability and payload potency differentiates ZW191 from other Potential best-in-class antibody FRα-TOPO1i ADCs The ZW191 antibody was selected for enhanced i
Slide 25: ZW191: Global Phase 1 Study in FRα-Expressing Solid Tumors
ZW191: Global Phase 1 Study in FRα-Expressing Solid Tumors (NCT06555744) USA Open-label, FIH, dose-escalation study USA Part 1: Dose Escalation N=~145 Part 2b: Dose Expansion Japan Part 2a: Dose Optimization Part 2b: Dose Expansion JPN Ovarian cancera Endometrial cancer and non-squamous NSCLC Advanc
Slide 26: ZW251: ADC Designed to Target GPC3-Expressing HCC
Optimized Design • Potential first-in-class ADC designed to treat GPC3-expressing HCC with a new MOA • Composed of a humanized IgG1 antibody conjugated to a novel camptothecin-based topoisomerase 1 inhibitor, ZD06519 • Intermediate drug-to-antibody ratio ~4 • Validated peptide cleavable linker seque
Slide 27: HCC Epidemiology and Current Treatment
HCC Epidemiology and Current Treatment HCC Burden Standard of Care for Systemic HCC • Globally 6th most common cancer and third most common • In the US, most patients receive IO-VEGF or IO-IO combinations in cause of death from cancer 1L; multi-targeted TKIs are a 2L option 5-Year Relative Survival,
Slide 28: ZW251: Potential Utility in Hepatocellular Carcinoma
ZW251: Potential Utility in Hepatocellular Carcinoma On track for clinical studies in mid-2025 Robust ADC Internalization Differentiated Modality Impressive Tolerability and Dose- and Cytotoxicity Demonstrates Anti-tumor Activity proportional PK in NHP ZW251 internalized in HCC cell line Non-GLP tox
Slide 29: ZW220: ADC Designed to Target NaPi2b-Expressing Cancers
Optimized Design1 • ADC targeting NaPi2b-expressing solid tumors • Comprised of a humanized IgG1 antibody conjugated to a moderate potency topoisomerase I inhibitor payload technology with bystander activity, ZD06519 • Intermediate drug-to-antibody ratio ~4 • Validated peptide cleavable linker seque
Slide 30: NaPi2b is Overexpressed in Multiple Cancers with High Unmet Medical Need
NaPi2b is Overexpressed in Multiple Cancers with High Unmet Medical Need 100 90 83% 81% 80% 80 Range: 77% 64-96% Range: Range: NaPi2b % Positivity by IHC 68-91% 70 66-84% 60 54% 53% 50 Ovarian 1) Banerjee et al. 2023. ESM O #145 40 2) Richardson et al. 2022. SG O #76 3) Levan et al. 2017. BM C Cance
Slide 31: ZW220: Potential Utility in Multiple Cancers
ZW220: Potential Utility in Multiple Cancers ZW220 Efficiently Internalizes and Anti-tumor Activity in Ovarian and Impressive Tolerability and Dose- Co-localizes with Lysosomes Lung Cancer Models proportional PK in NHP ZW220 (mAb) internalization in Ovarian Cancer cell line Non-GLP toxicology study
Slide 32: ZW209: Trispecific T Cell Engager Designed to Target DLL3
Optimized Design • Potential first-in-class TriTCE that targets DLL3-expressing tumor cells, and CD3 and CD28 on T cells. • TriTCE with potentially optimized TAA, CD3, CD28 binding affinity and geometry using Azymetric™ and EFECT™ platforms. • Leverages obligate cis-T cell binding and conditional CD
Slide 33: DLL3 is an Ideal Target to Evaluate TriTCE Co-stim Platform
DLL3 is an Ideal Target to Evaluate TriTCE Percentage of Patients with DLL3+ Tumors (%) Co-stim Platform, with 85% Opportunities in Multiple 77% 77% Cancers 17% 74% 13% 8% TPS ≥ 1% 12% TPS ≥ 25% Responsiveness of DLL3-expressing tumors to TCE modality validated with Imdelltra™ and 17% TPS ≥ 50% othe
Slide 34: CD28 Co-stimulatory T Cell Engager Approaches
CD28 Co-stimulatory T Cell Engager Approaches Bispecific CD28 T cell Engagers CD28 x TAA +/- PD1 CD28 x TAA + CD3 x TAA Limitations: Limitations: Initial clinical activity for CD28-TAA • Optimized for single agent activity and strong CD28 agonism, potential for +PD1, but potential toxicity due to si
Slide 35: ZW209: Mediates Enhanced and Sustained Cytotoxicity
ZW209: Mediates Enhanced and Sustained Cytotoxicity ZW209 demonstrates conditional CD28 binding and target-dependent anti-tumor activity Conditional Binding of CD28, Improved T Cell Proliferation, Improved Cytotoxicity Over Requiring Co-engagement of CD3; Memory T Cell Expansion and Bispecifics in L
Slide 36: ZW209: Enhanced Anti-Tumor Activity and Favorable Safety Profile
ZW209: Mediates Enhanced Anti-Tumor Activity and Favorable Safety Profile in In Vitro and Animal Studies ZW209 Mediates Enhanced Anti-Tumor Activity In Vivo Compared to Well Tolerated in Non-Human Tumour Volume (mm3) - NCI-H82 Donor H Benchmark Bispecific TCE inFabHumanized Tumour Volume (mm3) - NCI
Slide 37: AD-VAN-CE Portfolio: Progressing First In Class Therapeutics
- AD-VAN-CE Portfolio: Progressing “First In Class” Therapeutics 1. Focus on novel “first in class” multi-functional therapeutics: novelty of modality, mechanism of action (MoA), and/or targeting strategy. Disruptive therapeutics with high potential benefit to patients. 2. Build on competitive edge
Slide 38: ZW1528: Bispecific Designed to Address Respiratory Inflammation
Optimized Design • IL-4Rα x IL-33 bispecific molecule that inhibits multiple pathways within Anti-IL4Rα Anti-IL-33 complex pathophysiology of inflammation in diseases such as mixed- type COPD • In-house antibody discovery of novel anti-IL4Rα and IL-33 paratopes • Native IgG-like geometry Differentia
Slide 39: Bispecific Antibody Therapeutics for AIID and Hematology Oncology
Bispecific Antibody Therapeutics as the Potential Answer to Complex Biology of AIID and Hematology Oncology Patients Clinical Science Technology • Serious, difficult-to-treat diseases Clinically validated targets Clinically validated platform (e.g., ALL, cHL, MM, COPD, and NHL) Benefits of combinati
Slide 40: ZW1528: A Potential New Treatment Option in COPD
ZW1528: A Potential New Treatment Option in COPD Potently blocks two complementary pathways of respiratory inflammation, while aligning with requirements for successful AIID therapeutics Effectively Blocks of IL-4/13 and Demonstrates Biomarkers of IL- Effectively Blocks Complementary IL-33 Signaling
Slide 41: Multiple Candidates in Development Offer Strategic Pivot Points
Multiple Candidates in Development Offer Strategic Pivot Points ZW1528 ZW220 ZW209 Preclinical Development Decision Pathway Factors ZW251 Optimal dose Tolerability and safety ZW191 Early signs of anti-tumor activity ZW171 Proof of targeted therapy: strong relationship between expression levels and a
Slide 42: Executive Summary
Executive Summary With nomination of Recent approval of ADVANCE portfolio Clear decision-making ZW209, 5x5 solid tumor zanidatamab broadly diversified into processes to advance portfolio construction is demonstrates our hematological cancers and or cease development 18 months ahead of experience and
Slide 43: Meaningful Catalyst Events Anticipated Throughout 2025 & 2026
Meaningful Catalyst Events Anticipated Throughout 2025 & 2026 2025 2026 Potential regulatory decision in Pivotal Phase 3 top-line PFS data Expected IND submission for EU expected for zanidatamab in 2L readout in 1L GEA for zanidatamab ZW209 (DLL3) in 1H 2026 BTC targeted by our partner Jazz in 2H 20
Slide 44: Company Contacts
Company Contacts Investor Relations Media Relations Shrinal Inamdar Diana Papove Senior Director, Investor Relations Senior Director, Corporate Communications ir@zymeworks.com media@zymeworks.com +1 604 678 1388 +1 604 678 1388 Nasdaq: ZYME | zymeworks.com