ZW191 demonstrates encouraging anti-tumor activity in heavily pretreated ovarian and endometrial cancers, regardless of FRα expression
Confirmed objective response rate (cORR) of 61% at doses 6.4-9.6 mg/kg in platinum resistant ovarian cancer
Median duration of response was not reached at the time of data cutoff, and median progression-free survival was 7.6 months in ovarian and endometrial cancer cohorts
Favorable tolerability profile and broad therapeutic window support continued clinical development

VANCOUVER, British Columbia, April 21, 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 results from the dose-escalation part of the Phase 1 study for ZW191, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), at the 2026 American Association for Cancer Research (AACR) Annual Meeting.

The data from Part 1 of the ongoing global Phase 1 study (ZWI-ZW191-101), highlight a compelling combination of anti-tumor activity and manageable safety in patients with advanced, heavily pretreated solid tumors, including ovarian and endometrial cancers.

"We are highly encouraged by the initial clinical data for ZW191, which reinforce the strength of our ADC platform and its ability to generate differentiated therapeutics," said Sabeen Mekan, M.D., Senior Vice President and Chief Medical Officer at Zymeworks. "The breadth and durability of responses, along with activity across varying levels of FRα expression, support further development of ZW191 as a potential best-in-class agent for patients with ovarian and endometrial cancers."

Part 2a, the dose-optimization portion of the study evaluating patients with ovarian cancer at doses of 6.4 mg/kg and 9.6 mg/kg, has completed enrollment, with participants recruited globally across North America, Europe, and Asia-Pacific. The data from Part 2a will determine the recommended dose for any future registration studies.

Key Findings

In platinum resistant ovarian cancer patients, ZW191 demonstrated a cORR of 56% across all dose levels, with tumor regression observed in 68% of patients and disease control achieved in 94%. Notably, ZW191 demonstrated compelling anti-tumor activity in the 6.4-9.6 mg/kg dose range regardless of FRα expression, with a cORR of 61% observed in ovarian and 57% in endometrial cancers, with disease control observed in 100% of patients. These findings highlight the potential for ZW191 to benefit a broad patient population, including those with low or heterogeneous target expression.

In endometrial cancer, ZW191 showed a cORR of 40% across all dose levels and 57% in the 6.4-9.6 mg/kg cohort, with disease control rates of 80% and 86%, respectively. Responses were observed regardless of FRα expression levels, suggesting potential activity across a broad patient population.

Across ovarian and endometrial cancer cohorts, responses were observed early, with a median time to response of 1.4 months. Median duration of response was not reached at the time of data cutoff, and median progression-free survival was 7.6 months.

ZW191 was well tolerated and safely administered up to 11.2 mg/kg. Severe (grade ≥3) treatment-emergent adverse events (TEAEs) occurred in 55% of patients treated with ZW191, most of which were grade 3. The most common grade ≥3 events were neutropenia (24%), anemia (20%), and thrombocytopenia (12%). Grade 4 events were infrequent, and one grade 5 event was reported at the highest dose level and was not treatment-related. Serious TEAEs occurred in 35% of patients, and 20% discontinued due to adverse events. Overall, the safety profile was manageable with no unexpected signals.

"These data demonstrate the potential of ZW191 to deliver meaningful clinical benefit in patients with heavily pre-treated gynecological tumors with limited options," said Patricia LoRusso, DO, PhD (hc), FAACR and lead author. "The combination of encouraging response rates and manageable safety profile supports further development of this therapy, particularly in ovarian and endometrial cancers where new treatment options are urgently needed."

ZW191's differentiated profile, including a high drug-to-antibody ratio and novel payload, support its potential to address key limitations of current therapies and expand the reach of FRα-targeted treatment approaches across multiple tumor types.

About ZW191

ZW191 is an antibody-drug conjugate engineered to target a protein called folate receptor-⍺ found in ~75% of high-grade serous ovarian carcinomas,¹ over 50% of endometrial cancers^,2,3 and ~70% of lung adenocarcinomas⁴. ZW191's differentiated design strongly supports its ability to internalize into FR⍺-expressing cells with the potential to release bystander active topoisomerase-1 inhibitor (ZD06519), a novel proprietary payload developed by Zymeworks to kill tumor cells.

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.

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 the potential safety profile and therapeutic effects of Zymeworks' product candidates; Zymeworks' development of product candidates; status of studies and the related data; anticipated clinical data presentations; 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.

Contacts:

Investor Inquiries:

Shrinal Inamdar

Vice President, Investor Relations

(604) 678-1388

ir@zymeworks.com  

Media Inquiries:

Diana Papove

Vice President, Corporate Communications

(604) 678-1388

media@zymeworks.com

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¹ Köbel, M., Madore, J., Ramus, S. et al., Br J Cancer 111, 2297–2307 (2014).

²May B, Conway N, Truong T, Linhart S, et al. FRα, B7-H4, & HER2 Expression in Endometrial Cancer: Assessing the Promise of Antibody Drug Conjugate Therapies. Presented at: SGO 2025 Winter Meeting; January 30 - February 1, 2025; Whistler, British Columbia, Canada.

³ Senol S, Ceyran AB, Aydin A, Zemheri E, Ozkanli S, Kösemetin D, Sehitoglu I, Akalin I. Folate receptor α expression and significance in endometrioid endometrium carcinoma and endometrial hyperplasia. Int J Clin Exp Pathol. 2015 May 1;8(5):5633-41.

⁴ O'Shannessy DJ, et al., Oncotarget. 2012 Apr; 3(4):414-25.

Zymeworks Presents New Phase 1 Data for ZW191, a Folate Receptor Alpha-Targeting ADC at AACR Annual Meeting 2026