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Nasdaq: ZYME | zymeworks.com 3Q 2025 Results Conference Call and Webcast November 6, 2025
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2 Legal Disclaimer This presentation and the 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 1934, as amended. Forward-looking statements in this presentation and the accompanying oral commentary include, but are not limited to, statements that relate to Zymeworks’ expectations regarding implementation of its strategic priorities; anticipated regulatory submissions and the timing thereof; the anticipated benefits of its collaboration agreements with Jazz, BeiGene and other partners, including Zymeworks’ ability to receive any future milestone payments and royalties thereunder and the an ticipated timing thereof; anticipated actions by partners and the timing thereof; the potential addressable market of Zymeworks’ produc t candidates; the timing of and results of interactions with regulators; Zymeworks’ plans for preclinical and clinical development of its product candidates and enrollment in its trials, including any cessation or suspension thereof; the timing and status of ongoing and future studies and the related data; extrapolations or comparisons of results derived from independent studies which are subject to misinterpretation, assumptions or caveats of each study; anticipated preclinical and clinical data presentations; anticipated poster presentations; preclinical and clinical development progress and expectations regarding future regulatory submissions, filings and approvals and the timing thereof; the timing of and results of interactions with regulators; potential safety profile, therapeutic effects and commercial potential of Zymeworks’ product candidates; the evolution of and plans relating to Zymeworks’ business strategy related to anticipated and potential future royalty streams and existing and potential new partnerships; expected financial performan ce and future financial position; the commercial potential of technology platforms and product candidates; Zymeworks’ ability to satisfy potential regulatory and commercial milestones with existing and future partners; the timing and status of ongoing and future studies and the release of data; anticipated continued receipt of revenue from existing and future partners; Zymeworks’ early stage pipeline; anticipated sufficiency of existing cash resources and certain anticipated regulat ory milestone payments to fund Zymeworks’ planned operations into the second half of 2027; Zymeworks’ ability to execute new collaborations and partnerships and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “on track”, “progress”, and similar expressions, or any discussion of strategy, are intended to identify forward-looking statements. 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 are based upon Zymeworks’ current expectations and various assumptions, including, without limitation, Zymeworks’ examination of historical operating trends. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation: any of Zymeworks’ or its partners’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; Zymeworks may not achieve milestones or receive additional payments under its collaborations; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of new or changing laws and regulations; marke t conditions, including the impact of tariffs; potential negative impacts of FDA regulatory delays and uncertainty and new policies implemented under the current administration, including executive orders, changes in the leadership of federal agenc ies such as the FDA, staff layoffs, budget cuts to agency programs and research, and changes in drug pricing controls; the impact of pandemics and other health crises on Zymeworks’ business, research and clinical development plans and timelines and results of operations, including impact on its clinical trial sites, collaborators, and contractors who act for or on Zymeworks’ behalf; zanidatamab may not be successfully commercialized; Zymeworks’ evolution of its business strategy related to anticipated and potential fu ture milestones and royalty streams and existing and potential new partnerships may not be successfully implemented; clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collabor ators’ product candidates; Zymeworks’ assumptions and estimates regarding its financial condition, future financial performance and estimated cash runway may be incorrect; inability to maintain or enter into new partnerships or strategic col laborations; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission (copies of which may be obtained at www.sec.gov and www.sedarplus.ca). Although Zymeworks believes that such forward-looking statements are reasonable, there can be no assurance they will prove to be correct. Investors should not place undue reliance on forward-looking statements. The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward -looking statements to reflect new information, future events or circumstances, or to reflect the occurrences of unanticipated events.
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3 3Q 2025 Earnings Results Call Agenda Leone Patterson, MBA, CPA EVP, CBO and CFO • Business Update • Financial Update • Q&A • R&D Update • Q&A Paul Moore, Ph.D. CSO Ken Galbraith Chair and CEO • Clinical Updates • Q&A Sabeen Mekan, MD SVP Clinical Development • Q&A
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Leone Patterson, MBA, CPA FINANCIAL UPDATE 4 Executive Vice President, Chief Business and Financial Officer
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Pipeline Progress Progress on both clinical and preclinical programs within our wholly-owned product pipeline: • ENA Conference: Preliminary Phase 1 data on ZW191 provides early validation of ADC platform • First Patient Dosed in our Phase 1 clinical trial of ZW251, a DAR4 ADC targeting GPC3 • ERS Conference: Preclinical data presented on ZW1528, a novel IL-4Rα x IL-33 bispecific Partnership Progress Financial Highlights Continued Progress Across Business in Q3 2025 • J&J Innovative Medicine Initiated Phase 3 study for pasritamig (JNJ- 78278343) triggering $25.0M development milestone • Earned royalties of $1.0 million based on Ziihera® net product sales by Jazz and BeOne for 3Q-2025 • As of November 4, completed share repurchases of $22.7 million of the remaining $30.0 million of our share repurchase program for 1,439,068 shares of the Company’s common stock at an average price per share of $15.80 5 ADC: antibody-drug conjugate; ENA: AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics; DAR4: drug -to-antibody ratio of 4; ERS: European Respiratory Society Congress; ESMO: European Society for Medical Oncology; FIH: First-in-human; GPC3: glypican 3; ITT: intention-to-treat; mCRC: Metastatic Colorectal Cancer; OS: Overall Survival; PFS: Progression-free survival • In October 2025, at EMSO our partner Jazz presented a trial-in-progress poster on the DiscovHER PAN-206 phase 2 study of zanidatamab in HER2- overexpressing solid tumors, as well as a two-year follow-up in first-line mCRC. • In November 2025, Jazz announced that the ITT population for the primary PFS and interim OS analyses of the HERIZON-GEA-01 trial will include the full patient population enrolled in the study of 920 patients. • Also, at ESMO, J&J Innovative Medicine presented new data on Translational Analyses of T-cell Phenotypes and Their Association with Clinical Efficacy in the FIH Trial of Pasritamig in mCRC.
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$ 25.3 M $ 2.5 M $1.4 M $ 1.0 M $13.5M 3Q 2025 3Q 2024 Royalty Research support fee & drug supply Milestones 6 3Q 2025 Revenues, Operating Expenses and Cash Resources Revenue (USD) $45.8M • $25.3M of milestone and research period extension fee recognized in 3Q- 2025 from J&J and Merck. • $1.0M of royalty revenues from Jazz and BeOne. $34.4M $15.0M $15.7M $29.2M Cash, Cash equivalents and Marketable Securities (USD) $324.2M $333.4M • Decrease in cash resources for 3Q-2025 YTD due to cash used in operations offset by milestone receipts. • $16.2M was incurred to 3Q-2025 under our stock repurchase program. $ 35.6 M $ 36.4 M $ 14.1 M $ 13.9 M 3Q 2025 3Q 2024 R&D G&A Operating Expenses (USD) $ 299.4 M $ 324.2 M 3Q 2025 4Q 2024 • Slight decrease in R&D spend due to program mix and timing partially offset by higher stock-based compensation expense.
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Sabeen Mekan, MD CLINICAL DEVELOPMENT UPDATE 7 Senior Vice President, Clinical Development
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8 ZW191 Demonstrates a Favorable Clinical Safety Profile a. Percentages calculated based on the number of participants in the DLT evaluable set (n=25; n=5 at dose level 6.4 mg/kg). Treatment is ongoing and not all participants have completed the DLT window. DLT: dose-limiting toxicity; TRAE: treatment-related adverse event; AE: adverse event. TRAE, n (%) ZW191 1.6 mg/kg (n=3) ZW191 3.2 mg/kg (n=3) ZW191 4.8 mg/kg (n=4) ZW191 6.4 mg/kg (n=10) ZW191 8.0 mg/kg (n=11) ZW191 9.6 mg/kg (n=8) ZW191 11.2 mg/kg (n=2) Total (n=41) Any TRAE 1 (33) 3 (100) 3 (75) 8 (80) 10 (91) 6 (75) 2 (100) 33 (80) Grade ≥3 TRAE 0 1 (33) 0 1 (10) 4 (36) 1 (13) 0 7 (17) TRAE leading to dose interruption 0 2 (67) 0 0 1 (9) 0 0 3 (7) TRAE leading to dose reduction 0 0 0 1 (10) 1 (9) 0 0 2 (5) DLT eventa 0 0 0 1 (20) 0 0 0 1 (4) No serious TRAEs, discontinuations due to AEs, or deaths reported Data cutoff: September 10, 2025 Presented at 2025 AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics – Poster: LB-A011
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9 ZW191 Demonstrates a Potential Best-In-Class Efficacy Profile Best percent change in target lesion size from baseline (n=27) Best response ZW191 1.6 mg/kg (n=3) ZW191 3.2 mg/kg (n=3) ZW191 4.8 mg/kg (n=4) ZW191 6.4 mg/kg (n=7) ZW191 8.0 mg/kg (n=4) ZW191 9.6 mg/kg (n=3) ZW191 6.4-9.6 mg/kg (n=14) Total (n=24) PR, n (%)a 0 2 (67) 1 (25) 4 (57) 2 (50) 3 (100) 9 (64) 12 (50) cPR, n (%) 0 2 (67) 1 (25) 3 (43) 1 (25) 0 4 (29) 7 (29) SD, n (%) 1 (33) 1 (33) 2 (50) 3 (43) 2 (50) 0 5 (36) 9 (38) PD, n (%) 2 (67) 0 1 (25) 0 0 0 0 3 (13) aPR includes confirmed and unconfirmed. The 5 participants with unconfirmed PR are all awaiting confirmation. Note: Percentages are out of gynecological cancer (OC and EC) participants. cPR: confirmed partial response; EC, endometrial cancer; OC, ovarian cancer; PD: progressive disease; PR: partial response; RECIST v1.1: Response Evaluation Criteria in Solid Tumors version 1.1; SD: stable disease Preliminary efficacy for response-evaluable participants with gynecological cancer 27 participants were response-evaluable by having at least 1 post-baseline scan. Response based on RECIST v1.1 (response and progression defined as -30% and +20% change from baseline, respectively). EC: endometrial cancer; FRα: folate receptor alpha; LC: non-small cell lung cancer; OC: ovarian cancer; RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1 Data cutoff: September 10, 2025 Presented at 2025 AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics – Poster: LB-A011
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10 ZW191: Next Steps Data-Driven Development • Building confidence in our ADC platform through safety, pharmacokinetics, and efficacy with emerging clinical data Optimization & Differentiation • 11.2 mg/kg dose defined as MTD since this data-cut • Randomized dose optimization to begin in 4Q-2025 in platinum resistant ovarian cancer at 9.6 and 6.4 mg/kg doses (~30 pts/cohort) • Early data supports best-in-class potential Strategic Growth Potential • Emerging data will inform registration and combination strategies, including earlier-line opportunities • In parallel, partnership discussions are underway to further refine and accelerate development
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11 ZW251: Phase 1 Study in Glypican 3-Expressing Hepatocellular Carcinoma (HCC) (NCT07164313) Part 1: Dose Escalation (~6 dose levels; n=60) ZW251 Dose Level 1 X mg/kg Q3W ZW251 Dose Level 2 X mg/kg Q3W ZW251 Dose Level 3 X mg/kg Q3W ZW251 Dose Level 4 X mg/kg Q3W ZW251 Dose Level 5 X mg/kg Q3W ZW251 Dose Level 6 X mg/kg Q3W Treatment until disease progression, unacceptable toxicity, or withdrawal of consent Key Eligibility Criteria • HCC advanced or metastatic • Progressed on SOC treatment • Measurable by RECIST 1.1 • Child-Pugh class A • ECOG 0-1 • Adequate organ function ADA: anti-drug antibody; BOR: best overall response; DCR: disease control rate; DOR: duration of response; ECOG: Eastern Cooperative Oncology Group performance status; ORR: objective response rate; PD: pharmacodynamics; PK: pharmacokinetics; Q3W: every 3 weeks; RECIST: Response Evaluation Criteria in Solid Tumors; SOC: standard of care; R Dose A Dose B Part 2: Dose Optimization (n=40) Primary Endpoints Secondary Endpoints • Safety and tolerability • ORR (Part 2) • PK, ADA, • DOR, DCR, PFS, ORR (Part 1)
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Paul Moore, Ph.D. RESEARCH & DEVELOPMENT UPDATE 12 Chief Scientific Officer
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92 ZW191 Phase 1 Data Provides Early Validation of ADC Platform and Design Philosophy ZW191 ZW251 ZW220 ZW327 ZW318 Target FRα GPC3 NaPi2b Ly6E PTK7 Various Payload ZD06519 (TOPO1i) ZD06519 (TOPO1i) ZD06519 (TOPO1i) ZD06519 (TOPO1i) ZD06519 (TOPO1i) Targeted small molecule, Novel cytotoxic, dual payload Potential Indications OVCA, EC, NSCLC HCC OVCA, EC, NSCLC Pan Tumor NSCLC, TNBC Various Clinical Assets Preclinical Assets Next Gen
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14 ZW171 Phase 1 Provides Learnings for Next-Gen T Cell Engager Pipeline Oncology: Solid Tumors ZW171 Target: MSLN x CD3 Format: T Cell Engager Strategy: 2+1 Novel CD3 Epitope Azymetric and EFECT mutations QSP Modelling for FIH & Dose Projections Subcutaneous Delivery Step Up Dosing ZW209 Target: DLL3xCD3xCD28 Format: TriTCE Co-Stim Strategy: 1 + 1 + 1 Incorporation of CD3-dependent CD28 co-stimulation to enhance TCE-mediated antitumor activity in solid tumors by overcoming low T cell infiltration, T cell anergy and enhancing sustainability of T cell response Clinical DesignMolecular Design * * Design shown for representative purposes only CD28 DLL3 CD3 CD3 MSLN MSLN
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Diverse Potential Revenue Streams from Existing Partnerships • Near-Term Revenue Catalysts: Continued royalties from Jazz and BeOne Medicines for Ziihera® expected in 2025. • Long-Term Growth Potential: Wholly-owned assets provide flexibility for future licensing and royalty opportunities. 15 1 Current stage represents the current preclinical, clinical or commercial stage of development for the particular program, as applicable. 2 Tiered royalties of up to 19.5% of net sales in BeOne territories, increasing to up to 20% when cumulative amounts forgone as a result of a royalty reduction of 0.5% reaches a cap in the low double-digit millions of dollars. 3 Represents potential future milestone payments following recognition of $25.0 million development milestone in September 2025 . Except as otherwise indicated, the information is provided as at September 30, 2025. The information included in the table ab ove presents a summary of key aspects of our collaboration and licensing agreements. For additional information regarding the terms and conditions of our collaboration and licensing agreements, please refer to “Item 1. Business – Strategic Partnerships and Collaborations” of our Annual Report on Form 10-K for the year ended December 31, 2024 filed with the SEC on March 5, 2025, and the other information included in the Qu arterly Report on Form 10-Q for the quarter ended September 30, 2025. 15 Program & Platform Partner Therapeutic Indication Current Stage1 Potential Future Milestone Payments Royalty Rate Bispecific Antibody Azymetric | EFECT JNJ-78278343 CD3 x KLK2 Bispecific Azymetric | EFECT Bispecific Antibody Azymetric | EFECT Bispecific Antibody Azymetric | EFECT Bispecific Antibody Azymetric Zanidatamab Azymetric | EFECT Ziihera® (zanidatamab-hrii) Azymetric | EFECT Marketed in first indication (BTC) Marketed in first indication (BTC) Phase 3 Phase 1 Phase 1 Preclinical Phase 1 Castration-Resistant Prostate Cancer Oncology Undisclosed Immuno-Oncology Infectious Disease/Undisclosed HER2-expressing Cancer HER2-expressing Cancer Up to $1.36 billion Up to $144 million Up to $434 million3 Up to $313 million Up to $921.8 million Up to $230 million Up to $1.1 billion Tiered royalties up to 19.5% of net sales in BeOne territories2 Tiered worldwide royalties in the mid-single digit percentages Tiered worldwide royalties on sales Tiered worldwide royalties on sales Tiered worldwide royalties from low single digit percentages up to 10% Tiered worldwide royalties in the low to mid-single digit percentages Tiered worldwide royalties between 10% to 20% other than in BeOne territories Bispecific Antibody Azymetric | EFECT Preclinical Up to $1.1 billion Tiered worldwide royalties in the low single digit percentagesUndisclosed
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Q&A 16 Ken Galbraith Chair & CEO Paul Moore, Ph.D. CSO Leone Patterson, MBA, CPA EVP, CBO and CFO Sabeen Mekan, MD SVP Clinical Development