Zymeworks Announces Decision to Discontinue Clinical Development of ZW171, a Mesothelin-directed T cell Engager
Zymeworks (Nasdaq: ZYME) has announced the discontinuation of clinical development for ZW171, a T cell engager targeting mesothelin-driven cancers. The decision follows the completion of Phase 1 trial dose escalation cohorts in ovarian cancer and non-small cell lung cancer patients.
While cytokine release syndrome was manageable, the trial revealed dose-limiting toxicities related to mesothelin-targeted effects. The company determined that further dose evaluation would not support a favorable benefit-risk profile. Current trial participants may continue treatment at their investigator's discretion.
Zymeworks continues to advance other pipeline candidates, including the ongoing Phase 1 trial of ZW191, planned Phase 1 study for ZW251 in 2025, and an IND filing for ZW209 in early 2026.
Zymeworks (Nasdaq: ZYME) ha annunciato la sospensione dello sviluppo clinico di ZW171, un agente che recluta cellule T mirato ai tumori guidati da mesotelina. La decisione segue il completamento dei cohort di escalation di dose della Fase 1 in pazienti con carcinoma ovarico e carcinoma polmonare non a piccole cellule.
Sebbene la sindrome da rilascio di citochine sia stata gestibile, lo studio ha evidenziato tossicità limitanti la dose correlate agli effetti mirati sulla mesotelina. L’azienda ha ritenuto che ulteriori valutazioni di dose non avrebbero sostenuto un rapporto beneficio-rischio favorevole. I partecipanti attuali allo studio possono proseguire il trattamento a discrezione dell’investigatore.
Zymeworks prosegue lo sviluppo di altri candidati in pipeline, incluso l’attuale studio di Fase 1 su ZW191, lo studio di Fase 1 pianificato per ZW251 nel 2025 e una domanda IND per ZW209 prevista per i primi mesi del 2026.
Zymeworks (Nasdaq: ZYME) ha anunciado la interrupción del desarrollo clínico de ZW171, un reclutador de células T dirigido a cánceres impulsados por mesotelina. La decisión se toma tras completar las cohortes de escalado de dosis del ensayo de Fase 1 en pacientes con cáncer de ovario y cáncer de pulmón no microcítico.
Aunque el síndrome de liberación de citocinas fue manejable, el ensayo reveló toxicidades limitantes de dosis relacionadas con los efectos dirigidos a la mesotelina. La compañía determinó que una mayor evaluación de dosis no respaldaría un perfil beneficio-riesgo favorable. Los participantes actuales del ensayo pueden continuar el tratamiento a discreción del investigador.
Zymeworks continúa avanzando con otros candidatos de su pipeline, incluido el ensayo de Fase 1 en curso de ZW191, el estudio de Fase 1 planificado para ZW251 en 2025 y una presentación IND para ZW209 a principios de 2026.
Zymeworks (Nasdaq: ZYME)는 메소텔린 기반 암을 표적하는 T세포 유도제인 ZW171의 임상 개발 중단을 발표했습니다. 이 결정은 난소암 및 비소세포폐암 환자를 대상으로 한 1상 용량 증량 코호트가 완료된 후 내려졌습니다.
사이토카인 방출 증후군은 관리 가능한 수준이었으나, 임상시험에서 메소텔린 표적 효과와 관련된 용량 제한 독성이 확인되었습니다. 회사는 추가 용량 평가가 유리한 이익-위험 프로파일을 뒷받침하지 못할 것으로 판단했습니다. 현재 시험 참가자는 담당 연구자의 재량에 따라 치료를 계속할 수 있습니다.
Zymeworks는 진행 중인 ZW191의 1상 시험, 2025년 예정된 ZW251의 1상 연구, 그리고 2026년 초 예정된 ZW209에 대한 IND 제출을 포함한 다른 파이프라인 후보 개발을 계속 진행하고 있습니다.
Zymeworks (Nasdaq: ZYME) a annoncé l’arrêt du développement clinique de ZW171, un activateur de cellules T ciblant les cancers dépendants de la mésothéline. La décision suit l’achèvement des cohortes d’escalade de dose de l’essai de Phase 1 chez des patients atteints de cancer de l’ovaire et de cancer du poumon non à petites cellules.
Bien que le syndrome de libération de cytokines ait été maîtrisable, l’essai a mis en évidence des toxicités limitantes liées à la dose associées aux effets ciblant la mésothéline. La société a estimé que de nouvelles évaluations de dose ne soutiendraient pas un profil bénéfice‑risque favorable. Les participants actuels à l’essai peuvent poursuivre le traitement à la discrétion de l’investigateur.
Zymeworks poursuit le développement d’autres candidats de sa pipeline, notamment l’essai de Phase 1 en cours pour ZW191, l’étude de Phase 1 prévue pour ZW251 en 2025 et un dossier IND pour ZW209 au début de 2026.
Zymeworks (Nasdaq: ZYME) hat die Einstellung der klinischen Entwicklung von ZW171 angekündigt, einem T‑Zell‑Engager, der auf mesothelingetriebene Tumore abzielt. Die Entscheidung folgt auf den Abschluss der Dosis-Eskalationskohorten der Phase‑1‑Studie bei Patientinnen/Patienten mit Ovarialkarzinom und nicht‑kleinzelligem Lungenkarzinom.
Obwohl das Zytokinfreisetzungssyndrom beherrschbar war, zeigte die Studie dosislimitierende Toxizitäten, die mit mesothelin‑gerichteten Effekten zusammenhängen. Das Unternehmen kam zu dem Schluss, dass weitere Dosisbewertungen kein günstiges Nutzen‑Risiko‑Profil unterstützen würden. Aktuelle Studienteilnehmende können die Behandlung nach Ermessen des Prüfarztes fortsetzen.
Zymeworks treibt weiterhin andere Pipeline‑Kandidaten voran, darunter die laufende Phase‑1‑Studie von ZW191, eine geplante Phase‑1‑Studie für ZW251 im Jahr 2025 und eine IND‑Einreichung für ZW209 Anfang 2026.
- Well-managed cytokine release syndrome in Phase 1 study
- Company maintains active development pipeline with multiple candidates
- Demonstrates disciplined portfolio management approach
- Discontinuation of ZW171 clinical development program
- Dose-limiting toxicities observed due to mesothelin-related off-tumor effects
- Unfavorable benefit-risk profile for further development
Insights
Zymeworks discontinues ZW171 cancer program due to safety concerns despite completing Phase 1 dose escalation, focusing resources on other pipeline candidates.
Zymeworks' decision to discontinue ZW171 represents a significant setback in their oncology pipeline. The mesothelin-targeting T cell engager was being evaluated for gynecological, thoracic, and digestive system cancers - all areas with substantial unmet needs. The termination came after completing the planned dose escalation portion of the Phase 1 trial and establishing a maximum tolerated dose.
The critical issue identified was an unfavorable benefit-risk profile due to dose-limiting toxicities consistent with mesothelin-related on-target off-tumor effects. This highlights a common challenge with mesothelin as a target - it's expressed not only on tumor cells but also on normal mesothelial cells lining the pleura, peritoneum, and pericardium. While cytokine release syndrome was manageable, the off-target toxicity created an insurmountable safety hurdle.
From a development perspective, this outcome illustrates the "fail fast" principle in biotechnology. Rather than continuing investment in a compound with fundamental safety limitations, Zymeworks is redirecting resources to more promising candidates including ZW191 (currently in Phase 1), ZW251 (Phase 1 expected in 2025), and ZW209 (IND filing planned for early 2026). This portfolio management approach, while disappointing for the mesothelin program, represents prudent resource allocation for a clinical-stage company with multiple candidates.
The disconnect between promising preclinical activity and clinical reality with ZW171 also reinforces the limitations of preclinical models in predicting human toxicity profiles, particularly for novel modalities like T cell engagers that have complex safety considerations.
VANCOUVER, British Columbia, Sept. 02, 2025 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company 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, today announced its decision to voluntarily discontinue clinical development of ZW171, a T cell engager designed to target gynecological, thoracic, and digestive system cancers.
ZW171 is designed to address cancers driven by mesothelin, a well-recognized but historically challenging target.
The decision to discontinue clinical development of ZW171 was based on completion of the planned cohorts of the dose escalation portion of the Phase 1 trial of ZW171 in patients with ovarian cancer and non-small cell lung cancer. After completing the planned dose escalation cohorts and establishing a maximum tolerated dose, Zymeworks determined that further dose evaluation in the current trial would be unlikely to support a benefit-risk profile consistent with the desired monotherapy target product profile. While cytokine release syndrome was well-managed in the Phase 1 study, dose-limiting toxicities were consistent with mesothelin-related on-target off-tumor toxicity. Ongoing participants in the Phase 1 trial will continue treatment at the discretion of their investigator, and participants who have discontinued treatment will continue safety follow-up as per the study protocol.
“While this is a disappointing outcome given the promising preclinical activity observed with ZW171, we are deeply grateful to the patients, providers, and caregivers for their support and participation in the ZW171 Phase 1 study,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “As part of Zymeworks’ disciplined approach to the management of our broad product portfolio, we are committed to careful and consistent evaluation of clinical progress for each product candidate to ensure our resources are directed towards those product candidates with the greatest potential impact for patients. We continue to advance our broader product pipeline, including the ongoing Phase 1 trial of ZW191 and the initiation of a Phase 1 study for ZW251 expected in 2025. We are also preparing an IND filing for ZW209, our DLL3-directed trispecific T cell engager, planned in the first half of 2026.”
About Zymeworks Inc.
Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat conditions such as cancer, inflammation, and autoimmune disease. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks 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. Zanidatamab has received accelerated approval from the U.S. FDA, conditional approval from the NMPA in China, and conditional marketing authorization from the European Commission for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. It is the first and only dual HER2-targeted bispecific antibody approved for this indication in the U.S., Europe, and China. Zanidatamab is also being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with multiple HER2-expressing cancers. Zymeworks is rapidly advancing a robust pipeline of wholly-owned product candidates, leveraging its expertise in both antibody drug conjugates and multispecific antibody therapeutics targeting novel pathways in areas of significant unmet medical need. A Phase 1 study for ZW191 is actively recruiting and ZW251 is expected to enter clinical trials in 2025. In addition to Zymeworks’ pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X.
Cautionary Note Regarding Forward-Looking Statements
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’ expectations regarding implementation of its strategic priorities; statements that relate to potential therapeutic effects and commercial potential of zanidatamab and Zymeworks’ other product candidates; Zymeworks’ plans for clinical development of its product candidates and enrollment in its clinical trials, including any cessation or suspension thereof; the timing and status of ongoing and future studies and the related data; potential safety profile and therapeutic effects of zanidatamab and Zymeworks’ other product candidates; expected financial performance and future financial position; the timing and status of ongoing and future studies and the release of data; 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 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 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; 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 future 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 collaborators’ 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 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.
Investor inquiries:
Shrinal Inamdar
Senior Director, Investor Relations
(604) 678-1388
ir@zymeworks.com
Media inquiries:
Diana Papove
Senior Director, Corporate Communications
(604) 678-1388
media@zymeworks.com
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