ZW191 demonstrates compelling anti-tumor activity in platinum-resistant ovarian cancer patients regardless of FRα expression level

Confirmed objective response rate (cORR) of 78.6% in FRα-positive (≥75% at PS2+) platinum-resistant ovarian cancer patients and 47.4% in FRα-negative patients (<75% at PS2+) across all dose levels studied

Median duration of response was not reached at the time of data cutoff, and median progression-free survival was 7.6 months across ovarian and endometrial cancer cohorts

Patient recruitment in dose optimization cohorts completed, with favorable tolerability profile and broad therapeutic window supporting continued clinical development

VANCOUVER, British Columbia, June 14, 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 presented new clinical data from the dose-escalation portion of its ongoing Phase 1 study evaluating ZW191, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), at the European Society for Medical Oncology (ESMO) Gynaecological Cancers Congress 2026.

The presentation highlights compelling anti-tumor activity in patients with platinum-resistant ovarian cancer (PROC) and in patients with endometrial cancer, including patients with both positive and negative FRα expression. The results further support the potential of ZW191 to address limitations of currently available and investigational FRα-targeted therapies and broaden treatment opportunities for patients with gynecologic cancers.

"We are highly encouraged by these data, which continue to demonstrate the differentiated profile of ZW191 and its potential to deliver meaningful clinical benefit across a broad population of patients with ovarian and endometrial cancers," said Sabeen Mekan, M.D., Senior Vice President and Chief Medical Officer of Zymeworks. "The response rate observed in FRα-positive ovarian cancer patients compares favorably with currently available therapies, while maintaining meaningful activity in patients with negative FRα expression. Together these encouraging data on durability, progression-free survival, and manageable safety profile further strengthen our confidence in the program and reinforce the ability of our ADC platform to generate differentiated therapeutics."

The analysis included efficacy data by FRα expression level from Part 1 of the ongoing Phase 1 study as of the March 9, 2026, data cutoff. FRα expression was assessed by immunohistochemistry and categorized using the Proportion and Staining Intensity, defined as the percentage of cells with 2+/3+ staining. Tumors were categorized as FRα-negative (<75%) or FRα-positive (≥75%).

Key Findings

Among response-evaluable PROC patients, ZW191 demonstrated a cORR of 78.6% in patients with FRα-positive tumors and 47.4% in patients with FRα-negative tumors across all dose levels. Disease control rates were 100.0% and 89.5%, respectively. Confirmed ORR in the overall PROC population was 58.8% across all dose levels studied and 65.2% in dose range of 6.4-9.6 mg/kg. These findings demonstrate meaningful anti-tumor activity across both FRα-positive and FRα-negative tumors as well as in the overall population.

In endometrial cancer patients with FRα-negative tumors, ZW191 demonstrated a cORR of 40.0% and a disease control rate of 80.0% across all doses evaluated.

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

ZW191 continued to demonstrate a favorable tolerability profile. Treatment-emergent adverse events (TEAEs) occurred in 98% of patients, with grade ≥3 TEAEs reported in 55% of patients. The most common grade ≥3 adverse events were neutropenia (24%), anemia (20%), and thrombocytopenia (12%). Serious TEAEs occurred in 35% of patients, and 20% of patients discontinued treatment due to adverse events. Overall, the safety profile was manageable and consistent with continued clinical development.

"These results further demonstrate the potential of ZW191 to provide meaningful clinical benefit for patients with difficult-to-treat gynecologic cancers," said Kosei Hasegawa, M.D., Ph.D., Saitama Medical University International Medical Center and presenting author. "The robust activity observed in FRα-positive ovarian cancer, together with encouraging responses in tumors with lower FRα expression, suggests ZW191 could expand the benefit of FRα-targeted therapy to a broader patient population."

Part 2a, the dose optimization portion of the Phase 1 study evaluating ZW191 in ~60 PROC patients randomized to either 6.4 mg/kg every three weeks or 9.6 mg/kg every three weeks, has completed enrollment. Data from Part 2a will be presented at a future medical meeting and are expected to inform dose selection for potential future development.

ZW191's differentiated profile, including its novel FRα-targeting antibody, ZD06519 payload, and high drug-to-antibody ratio, supports its potential to address key limitations of current therapies and broaden the applicability 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 carcinomas1, over 50% of endometrial cancers2,3 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 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.

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 K?bel, M., Madore, J., Ramus, S. et al., Br J Cancer 111, 2297?2307 (2014).

2 May 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, K?semetin 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.

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