Zymeworks Presents Initial Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺ at AACR-NCI-EORTC Conference
Zymeworks (NASDAQ: ZYME) reported preliminary Phase 1 clinical data for ZW191, an antibody-drug conjugate targeting folate receptor-α, presented Oct 23, 2025. As of Sep 10, 2025, 41 patients were enrolled (doses 1.6–11.2 mg/kg) with 85% remaining on treatment.
Key efficacy: among response-evaluable patients (n=27) overall ORR 44%; at 6.4–9.6 mg/kg ORR 53%. In gynecological cancers (n=24) ORR was 50% overall and 64% at 6.4–9.6 mg/kg. Responses began at 3.2 mg/kg and occurred with low/negative FRα expression.
Safety and next steps: no serious treatment-related AEs, discontinuations for AEs, or deaths reported. Common Grade ≥3 treatment-related AEs: anemia 10%, neutropenia 5%, thrombocytopenia 5%. MTD determined at 11.2 mg/kg; dose-optimization cohorts at 6.4 mg/kg and 9.6 mg/kg planned (~30 patients each) with dose optimization to start in 4Q-2025.
Zymeworks (NASDAQ: ZYME) ha riferito dati clinici preliminari di fase 1 per ZW191, un conjugato anticorpo-droghe che mira al recettore del folato-α, presentati il 23 ottobre 2025. Alla data del 10 settembre 2025, 41 pazienti sono stati arruolati (dosi 1.6–11.2 mg/kg) con l'85% ancora in trattamento.
Effetti chiave: tra i pazienti valutabili per risposta (n=27) ORR globale 44%; a 6.4–9.6 mg/kg ORR 53%. Nei tumori ginecologici (n=24) ORR globale 50% e 64% a 6.4–9.6 mg/kg. Le risposte hanno avuto inizio a 3.2 mg/kg e si sono verificate anche con espressione FRα bassa/negativa.
Sicurezza e prossimi passi: nessun evento avverso grave correlato al trattamento, interruzioni per AE o decessi riportati. Le AEs correlate al trattamento di grado ≥3 comuni: anemia 10%, neutropenia 5%, trombocitopenia 5%. MTD determinata a 11.2 mg/kg; coorti di ottimizzazione della dose a 6.4 mg/kg e 9.6 mg/kg pianificate (~30 pazienti ciascuna) con l'ottimizzazione della dose prevista per il 4Q-2025.
Zymeworks (NASDAQ: ZYME) informó datos clínicos preliminares de Fase 1 para ZW191, un conjugado anticuerpo- fármaco que apunta al receptor de folato-α, presentados el 23 de octubre de 2025. Al 10 de septiembre de 2025, se inscribieron 41 pacientes (dosis 1.6–11.2 mg/kg) con el 85% permaneciendo en tratamiento.
Eficacia clave: entre los pacientes evaluables para respuesta (n=27) ORR global 44%; a 6.4–9.6 mg/kg ORR 53%. En cánceres ginecológicos (n=24) ORR global 50% y 64% a 6.4–9.6 mg/kg. Las respuestas comenzaron a 3.2 mg/kg y se observaron incluso con expresión FRα baja/negativa.
Seguridad y próximos pasos: no se reportaron eventos adversos graves relacionados con el tratamiento, interrupciones por AEs, ni muertes. AEs relacionados con el tratamiento de grado ≥3 comunes: anemia 10%, neutropenia 5%, trombocitopenia 5%. La MTd se determinó en 11.2 mg/kg; cohortes de optimización de dosis en 6.4 mg/kg y 9.6 mg/kg planificadas (~30 pacientes cada una) con inicio de la optimización de dosis en el 4T-2025.
Zymeworks (NASDAQ: ZYME)는 ZW191에 대한 1상 예비 임상 데이터를 2025년 10월 23일에 발표했습니다. ZW191은 엽산 수용체-α를 표적으로 하는 항체-약물 결합체이며, 2025년 9월 10일 기준 41명의 환자를 등록했고(용량 1.6–11.2 mg/kg), 그 중 85%가 여전히 치료 중입니다.
효능 요약: 반응 평가 가능 환자(n=27)에서 전체 객관적 반응률(ORR) 44%; 6.4–9.6 mg/kg에서 ORR 53%. 자궁부속기관암 등 부인과 암에서(또는 gynecological cancers) (n=24) 전체 ORR 50%, 6.4–9.6 mg/kg에서 64%입니다. 반응은 3.2 mg/kg에서 시작되었고 FRα 발현이 낮거나 음성인 경우에도 발생했습니다.
안전성 및 향후 계획: 치료와 관련된 중대한 이상반응(AEs), AE로 인한 치료 중단, 사망은 보고되지 않았습니다. 치료와 관련된 3등급 이상 AEs로는 빈혈 10%, 호중구감소 5%, 혈소판감소 5%가 흔했습니다. 최대 내약용량(MTD)은 11.2 mg/kg으로 결정되었고, 용량 최적화 코호트는 각각 6.4 mg/kg 및 9.6 mg/kg로 계획되어 있으며(각 약 30명), 2025년 4분기 시작될 예정입니다.
Zymeworks (NASDAQ : ZYME) a publié des données cliniques préliminaires de phase 1 pour ZW191, un conjugué anticorps-médicament ciblant le récepteur du folate-α, présentées le 23 octobre 2025. À la date du 10 septembre 2025, 41 patients avaient été recrutés (doses 1,6–11,2 mg/kg) et 85% étaient toujours en traitement.
Efficacité clé : parmi les patients évaluables pour la réponse (n=27), l'ORR globale est de 44%; à 6,4–9,6 mg/kg, ORR de 53%. Dans les cancers gynécologiques (n=24), ORR globale de 50% et 64% à 6,4–9,6 mg/kg. Les réponses ont commencé à 3,2 mg/kg et se sont produites même avec une faible/negative expression de FRα.
Sécurité et prochaines étapes : aucun événement indésirable grave lié au traitement, ni interruptions pour événements indésirables, ni décès signalés. Les AEs liés au traitement de Grade ≥3 les plus courants : anémie 10%, neutropénie 5%, thrombocytopénie 5%. Le MTD a été déterminé à 11,2 mg/kg; des cohortes d’optimisation de dose à 6,4 mg/kg et 9,6 mg/kg sont prévues (~30 patients chacune) avec démarrage de l’optimisation de dose au cours du T4 2025.
Zymeworks (NASDAQ: ZYME) hat vorläufige Phase-1-Klinikdaten für ZW191, ein Antikörper-Wirkstoff-Konjugat, das auf den Folatrezeptor-α abzielt, veröffentlicht, präsentiert am 23. Oktober 2025. Stand 10. September 2025 wurden 41 Patienten eingeschlossen (Dosen 1,6–11,2 mg/kg); 85% befinden sich weiterhin in Behandlung.
Schlüsselergebnisse: Bei responstable Patienten (n=27) liegt das overall ORR bei 44%; bei 6,4–9,6 mg/kg beträgt die ORR 53%. In gynäkologischen Krebserkrankungen (n=24) beträgt die ORR 50% insgesamt und 64% bei 6,4–9,6 mg/kg. Die Antworten begannen bei 3,2 mg/kg und traten auch bei niedriger/negativer FRα-Expression auf.
Sicherheit und nächste Schritte: keine schwerwiegenden behandlungsbedingten AEs, keine Dekomplikationen aufgrund von AEs und keine Todesfälle berichtet. Häufige behandlungsbezogene AEs Grad ≥3: Anämie 10%, Neutropenie 5%, Thrombozytopenie 5%. Die MTD wurde bei 11,2 mg/kg festgelegt; Dosis- Optimierungs-Kohorten bei 6,4 mg/kg und 9,6 mg/kg geplant (je ca. 30 Patienten) mit Beginn der Dosisoptimierung im 4. Quartal 2025.
زيميووركس (بورصة ناسداك: ZYME) أصدرت بيانات سريرية تمهيدية للمرحلة 1 لـ ZW191، وهو مركب ضوئي-دوائي يستهدف مستقبل الفولات-α، مقدمة في 23 أكتوبر 2025. حتى 10 سبتمبر 2025، تم تسجيل 41 مريضاً (جرعات 1.6–11.2 mg/kg) وبقاء 85% في العلاج.
الكفاءة الأساسية: من بين المرضى القابلين لتقييم الاستجابة (n=27) معدل الاستجابة الشامل (ORR) 44%; عند 6.4–9.6 mg/kg ORR 53%. في سرطانات الفرج/أعضاء الأنثى (أورام نسائية) (n=24) ORR الكلي 50% و64% عند 6.4–9.6 mg/kg. بدأت الاستجابات عند 3.2 mg/kg ووقعت حتى مع انخفاض/سلبية تعبير FRα.
السلامة والخطط القادمة: لم تُبلَّغ عن أحداث جانبية خطيرة مرتبطة بالعلاج، ولا حالات توقف بسبب العوارض الجانبية، ولا وفيات. أكثر الأحداث الجانبية المرتبطة بالعلاج من الدرجة ≥3 هي: فقر الدم 10%، نقص العدلات 5%، نقص صفائح الدم 5%. تم تحديد الحد الأقصى للتحمل (MTD) عند 11.2 mg/kg؛ مخطط لمجموعات تحسين الجرعة عند 6.4 mg/kg و9.6 mg/kg (كل منها حوالي 30 مريضاً) مع بدء تحسين الجرعة في الربع الرابع من 2025.
Zymeworks（纳斯达克股票代码：ZYME）在2025年10月23日公布了ZW191的I期临床数据初步结果。ZW191是一种靶向叶酸受体-α的抗体药物偶联物。截至2025年9月10日，已入组41名患者（剂量1.6–11.2 mg/kg），其中85%仍在治疗中。
关键疗效：在可评估应答的患者中（n=27）总客观缓解率（ORR）为44%；在6.4–9.6 mg/kg剂量组ORR为53%。在妇科癌症组（n=24）总ORR为50%，6.4–9.6 mg/kg组为64%。应答起始于3.2 mg/kg，即使在FRα表达低/阴性的情况下也出现。
安全性与后续步骤：未报告与治疗相关的严重不良事件、因不良事件导致的中止或死亡。治疗相关的Grade ≥3不良事件常见为：贫血10%，中性粒细胞减少5%，血小板减少5%。MTD在11.2 mg/kg处确定；剂量优化队列设在6.4 mg/kg和9.6 mg/kg（各约30名患者），计划在2025年第四季度开始剂量优化。
- Response-evaluable ORR 44% (n=27)
- Gynecological cancers ORR 50% (n=24)
- High-dose window: ORR 53% at 6.4–9.6 mg/kg
- Gynecologic ORR 64% at 6.4–9.6 mg/kg
- MTD established at 11.2 mg/kg; two cohorts selected for optimization
- Response-evaluable population limited to 27 of 41 enrolled patients
- Grade ≥3 treatment-related anemia in 10% of patients
- Grade ≥3 neutropenia and thrombocytopenia each in 5%
Insights
Phase 1 data show early efficacy and tolerable safety for ZW191, supporting dose‑optimization and further development.
ZW191 produced meaningful objective response rates in a heavily pretreated population: overall ORR
The safety profile appears manageable for an ADC: no treatment‑related deaths, no discontinuations for AEs, and low rates of dose modifications or delays. The most common Grade ≥3 treatment‑related AEs were anemia (
These results justify near‑term milestones to track: completion of the two dose‑optimization cohorts, durability and depth of responses in the ~60 planned patients, and any emerging safety signals as exposure increases. Expect meaningful readouts over the next 6–12 months after dose optimization begins; those data will determine whether a registrational pathway can be defined.
- Preliminary efficacy data, combined with a tolerable safety profile, reinforce the potential of ZW191 in patients with advanced solid tumors, including ovarian, endometrial, and non-small cell lung cancer
64% overall response rate in gynecological cancers at doses ≥6.4mg/kg- Responses observed at all doses evaluated at 3.2mg/kg and above demonstrating wide therapeutic index of Zymeworks’ novel antibody-drug conjugate platform
- Dose optimization of ZW191 in ovarian cancer to initiate in 4Q-2025
- Investor and analyst call to be held today at 3:30 pm Eastern Time (ET)
VANCOUVER, British Columbia, Oct. 23, 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 preliminary results from a Phase 1 study evaluating ZW191, an antibody-drug conjugate (ADC) targeting folate receptor-alpha (FR⍺), at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics, being held October 22-26, 2025, in Boston, MA.
“These first clinical data from our Phase 1 study of ZW191 provide early validation of our innovative approach to designing novel ADCs, through combining a unique antibody design with our proprietary payload, ZD06519,” said Sabeen Mekan, MD, Senior Vice President of Clinical Development of Zymeworks. “We are encouraged by the early signs of anti-tumor activity and favorable safety profile in a heavily pretreated population, which supports best-in-class potential and strengthens our confidence in this approach. With dose optimization planned to begin in the fourth quarter of this year and additional candidates such as ZW251 advancing in development, we remain focused on delivering meaningful new treatment options for patients with challenging cancers.”
Key Findings
As of September 10, 2025, the study enrolled 41 patients from doses 1.6 to 11.2 mg/kg (which was ongoing as of this date) in a heavily pretreated patient population of platinum resistant ovarian cancer, metastatic endometrial cancer, and metastatic non-small cell lung cancer who were enrolled regardless of FR⍺ expression levels. The majority of patients (
- ZW191 exhibited promising preliminary anti-tumor activity:
- For all response-evaluable participants (n=27) across dose levels, objective response rate (ORR) was
44% ; across doses of 6.4 mg/kg to 9.6 mg/kg, ORR was53% . - For response-evaluable gynecological cancer participants (n=24) across dose levels, ORR was
50% ; across doses of 6.4 mg/kg to 9.6 mg/kg, ORR was64% . - Responses were observed beginning at the 3.2 mg/kg dose and in tumors with low/negative levels of FRα expression.
- For all response-evaluable participants (n=27) across dose levels, objective response rate (ORR) was
- ZW191 demonstrated a manageable safety profile, with low rates of dose modifications, dose delays, and Grade ≥3 treatment-related adverse events (AE).
-
- No serious treatment-related AEs, discontinuations due to AEs, or deaths were reported.
- The most common ≥ Grade 3 treatment-related AEs were anemia (
10% ), neutropenia (5% ) and thrombocytopenia (5% ).
-
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- These data represent a broad therapeutic window for ZW191 and provide the rationale for further investigation in advanced solid tumors.
Since this data-cut, 11.2 mg/kg has been determined as the maximum tolerated dose and based on safety, efficacy, and pharmacokinetic data, two dose levels – 6.4 mg/kg and 9.6 mg/kg – have been selected for dose optimization, with approximately 30 patients planned in each cohort. This next stage of development is designed to further evaluate ZW191’s clinical activity and safety to inform a registrational strategy.
“It is rewarding to see the scientific promise behind ZW191, including its novel antibody and payload technology, begin to translate into meaningful observations in the clinic,” said Patricia LoRusso, DO, PhD (hc), FAACR and lead author. “These early efficacy and safety findings represent an important step in exploring new treatment strategies for patients with advanced, aggressive cancers and I look forward to observing ZW191’s continued progress.”
Presentation Details
- Title: Preliminary Results From a Phase 1 First-in-Human Multicenter Open-Label Study Of ZW191, a Folate Receptor α–Targeting Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors
- Session: Poster Session A
- Date/Time: Thursday, October 23, 2025 at 12:30-4:00 pm ET
Investor & Analyst Call
A live webcast will be held today at 3:30 pm ET with lead author Patricia LoRusso, DO, PhD (hc), FAACR and Zymeworks senior management to discuss the data presented. Dial-in details and webcast replay available on Zymeworks’ website at https://ir.zymeworks.com/events-and-presentations.
About ZW191
ZW191 is an ADC engineered to target a protein called folate receptor-⍺ (FR⍺), found in ~
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’ data presentations and key findings; the timing and status of ongoing and future studies and the release of data; the potential therapeutic effects of and commercial potential of Zymeworks’ product candidates; Zymeworks’ preclinical pipeline; plans for product candidates’ next stages of development; the ability to advance product candidates into later stages of development and the timing of such advancement; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “anticipate”, “potential”, “will”, “on track”, “continue”, “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: clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; 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; 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 and new policies implemented under the current administration, including executive orders, 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 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; clinical trials and any future clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; 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
1 Köbel, M., Madore, J., Ramus, S. et al., Br J Cancer 111, 2297–2307 (2014).
2 O'Shannessy DJ, et al., Oncotarget. 2012 Apr; 3(4):414-25.
FAQ
What were ZW191 Phase 1 response rates reported by Zymeworks (ZYME) on Oct 23, 2025?
What dose levels of ZW191 will Zymeworks (ZYME) use in dose optimization in 4Q-2025?
What safety signals did Zymeworks report for ZW191 in the Phase 1 study?
What is the maximum tolerated dose (MTD) of ZW191 reported by Zymeworks?
Did ZW191 show activity in tumors with low or negative FRα expression?
How many patients were enrolled in the ZW191 Phase 1 study as of the data cut?
