Zymeworks Presents New Preclinical Data at AACR 2026 Highlighting Broad Antibody-Drug Conjugate Programs Including Novel RAS-Targeting Platform

• Six poster presentations showcase Zymeworks' next-generation ADC programs, including multiple first-in-class pan-RAS inhibitor ADCs 
• Data highlight efficacy, tumor-selective delivery, and favorable tolerability across multiple solid tumor models
• New programs include Ly6E, CLDN18.2, and PTK7-targeting ADCs, as well as novel payload and platform innovations
• New clinical data from Phase 1 trial of ZW191 to be presented in an oral presentation on April 21

VANCOUVER, British Columbia, April 17, 2026 (GLOBE NEWSWIRE) -- Zymeworks Inc. (NASDAQ:ZYME), a biotechnology company managing a portfolio of licensed healthcare assets while developing a diverse pipeline of novel, multifunctional biotherapeutics, today announced six poster presentations featuring new preclinical data from its antibody-drug conjugate (ADC) and payload development programs at the American Association for Cancer Research (AACR) Annual Meeting 2026.

"Our AACR presentations highlight the breadth and depth of our ADC platforms, including multiple novel approaches to targeting RAS-driven cancers," said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. "These data reinforce our strategy to develop differentiated therapeutics with the potential to improve efficacy while addressing key limitations of existing treatment approaches."

Poster Presentation Highlights

ZW191 - a differentiated FRα-targeted topoisomerase I antibody drug conjugate active in combination with standard of care drugs

Abstract: 1707

Session: Experimental and Molecular Therapeutics

ZW191 is a clinical-stage (NCT06555744) folate receptor alpha (FRα)-targeting antibody-drug conjugate featuring a novel antibody and a moderate-potency, bystander-active topoisomerase I inhibitor payload (TOPO1i), ZD06519, designed to drive improved efficacy and tolerability versus existing FRα-targeted ADCs. In nonclinical studies, ZW191 demonstrates activity across all levels of FRα expression and shows promising combination potential with standard-of-care therapies, supported by a favorable tolerability profile.

Key non-clinical findings include:

• Differentiated by its superior internalizing novel antibody and moderate potency novel TOPO1i payload.
• Favorable tolerability profile, attributed to moderate potency TOPO1i payload and moderate stability linker, potentially achieves higher ADC dosing, better tolerability and improved combination potential with standard of care chemotherapeutics.
• Nonclinical in vitro and in vivo studies support the efficacious combination of ZW191 with standard of care therapies across multiple modes of action.
  
  

A pan-RASi antibody drug-conjugate platform with high activity in RAS sensitive cancers

Abstract: 1642

Session Category: Experimental and Molecular Therapeutics

Zymeworks' RASi-ADC platform integrates novel tricomplex pan-RAS inhibitors into ADCs to enable tumor-selective delivery and improved therapeutic index.

Key findings include:

• Strong regressions observed in multiple tumor models at single doses as low as 1 mg/kg
• ADC delivery demonstrates improved tumor selectivity compared to orally administered RAS inhibitors
• Favorable tolerability observed in rodents and non-human primates
• Platform supports development of broadly applicable ADCs for RAS-mutated cancers

Development of ZW418, a biparatopic PTK7-targeting antibody-drug conjugate incorporating a novel pan-RAS inhibitor payload for the treatment of non-small cell lung cancer

Abstract: 4944

Session Category: Experimental and Molecular Therapeutics

ZW418 is a first-in-class biparatopic ADC targeting PTK7, designed to enhance binding, internalization, and delivery of a pan-RAS inhibitor payload in non-small cell lung cancer (NSCLC).

Key findings include:

• Strong anti-tumor activity observed across PTK7-expressing RAS-mutant NSCLC xenograft models, at doses as low as 1 mg/kg
• Biparatopic design enhances receptor engagement, internalization, and payload delivery
• Selective cytotoxicity in KRAS-mutant tumor cells while sparing normal tissues
• Favorable pharmacokinetics and tolerability support further development

ZW427, a Ly6E-targeting antibody-drug conjugate bearing a novel pan-RAS inhibitor payload for the treatment of RAS mutated cancers

Abstract: 7715

Session Category: Experimental and Molecular Therapeutics

ZW427 is a first-in-class ADC targeting Ly6E, designed to deliver a novel pan-RAS inhibitor payload to tumor cells in colorectal (CRC), pancreatic (PDAC), and lung cancers.

Key findings include:

• Robust anti-tumor activity observed across CRC, PDAC, and NSCLC xenograft models with a range of Ly6E expression
• Targeted delivery enables sustained RAS inhibition in tumors with reduced activity in normal tissues such as skin and colon
• Favorable tolerability observed in rodents and non-human primates at exposures exceeding projected efficacious doses
• Potential to improve efficacy and safety profile compared to small molecule pan-RAS inhibitors

ZW439, a novel CLDN18.2-targeting pan-RAS inhibitor antibody-drug conjugate for the treatment of RAS mutated pancreatic cancer

Abstract: 4556

Session Category: Experimental and Molecular Therapeutics

ZW439 is a novel ADC targeting CLDN18.2, designed to deliver a pan-RAS inhibitor payload in pancreatic ductal adenocarcinoma.

Key findings include:

• Strong anti-tumor activity observed in CLDN18.2-expressing RAS-mutant xenograft models, at doses as low as 1 mg/kg
• Target-dependent delivery of pan-RAS inhibitor payload with potent RAS pathway inhibition and cytotoxicity
• Robust bystander activity supports activity in heterogeneous tumors
• Favorable pharmacokinetics and tolerability compared to small molecule RAS inhibitors

Design and evaluation of mRNA translation inhibitors for use as antibody drug conjugate payloads

Abstract: 2062

Session Category: Experimental and Molecular Therapeutics

Zymeworks presented a novel class of eIF4A inhibitor payloads designed to inhibit mRNA translation and enable a new mechanism for ADC therapies.

Key findings include:

• Over 40 novel eIF4A inhibitor payloads synthesized spanning a range of potency and hydrophilicity
• Hydrophilic linker designs improve both efficacy and tolerability in vivo
• Demonstrated robust anti-tumor activity across multiple targets including HER2, TROP2, EGFR, Ly6E, and PTK7
• Represents a novel payload class with potential to overcome resistance to existing ADC payloads

Posters are available on the Company's website located at https://www.zymeworks.com/publications/.

Oral Presentation Details

Results from Part 1 dose escalation of ZWI-ZW191-101 study: Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)–targeting antibody-drug conjugate (ADC), in participants with advanced solid tumors

Abstract: CT306

Session: Advances in Precision Oncology

Lead author Patricia LoRusso, DO, PhD (hc), FAACR will present an updated data cut from the late breaking abstract on Tuesday, April 21, 2026 at 2:30 – 4:30 pm Pacific Standard Time (PST). The presentation will be available on the Company's website located at https://www.zymeworks.com/publications/ at the time of the session.

About Zymeworks Inc.

Zymeworks is a global biotechnology company managing a portfolio of licensed healthcare assets and developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, including cancer, inflammation, and autoimmune disease. Zymeworks' asset and royalty aggregation strategy focuses on optimizing positive future cash flows from an emerging portfolio of licensed products such as Ziihera® (zanidatamab-hrii) and other licensed products and product candidates, such as pasritamig. In addition, Zymeworks is also building a portfolio of healthcare assets that can generate strong cash flows, while supporting the development of innovative medicines. Zymeworks engineered and developed Ziihera, a HER2-targeted bispecific antibody using the Zymeworks' proprietary Azymetric™ technology and has entered into separate agreements with BeOne Medicines Ltd. (formerly BeiGene, Ltd.) and Jazz Pharmaceuticals Ireland Limited granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zymeworks is rapidly advancing a robust pipeline of product candidates, leveraging its expertise in both antibody drug conjugates and multispecific antibody therapeutics targeting novel pathways in areas of significant unmet medical need. Zymeworks' complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutics. These capabilities have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X.

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This press release includes "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 press release include, but are not limited to, statements that relate to Zymeworks' preclinical and clinical development of product candidates; status of studies and the related data; anticipated preclinical and clinical data presentations; potential safety profile and therapeutic effects of Zymeworks' product candidates; Zymeworks' implementation of its long-term strategy; 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", "preserve", "intend", "could", and similar expressions 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. 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 or royalties 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; market conditions, including the impact of tariffs; potential negative impacts of FDA regulatory delays and uncertainty around recent policy developments, changes in the leadership of federal agencies such as the FDA, staff layoffs, budget cuts to agency programs and research, and changes in drug pricing controls; the impact of global and regional geopolitical or public health developments 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' business strategy related to anticipated and potential future milestones and royalty streams and existing and potential new partnerships may not be successfully implemented; Zymeworks' evolution of its business strategy may not deliver meaningful shareholder returns; Zymeworks may be unsuccessful in actively managing and/or aggregating revenue generating assets alongside its active R&D operations; ongoing and future clinical trials may not demonstrate safety and efficacy of any of Zymeworks' or its collaborators' product candidates; data providing early validation of our antibody drug conjugate platform and next generation pipeline programs may not be replicated in future studies; 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 collaborations; 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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