- Partner presentations reinforce ability of proprietary Azymetric™ platform to develop clinically validated therapeutic antibodies
- Long-term outcomes and survival data for Ziihera® (zanidatamab-hrii), which was developed using Azymetric™, to be presented at ASCO and highlight its potential to transform the treatment landscape for first-line HER2-positive gastroesophageal cancer
- ZW171 Trial-in-Progress (TiP) poster at ASCO, ZW191 TiP poster at ESMO Gynaecological Cancers Congress; trial enrollment remains on track
VANCOUVER, British Columbia, May 22, 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 multiple presentations related to its oncology programs at upcoming medical conferences, including the American Society of Clinical Oncology (ASCO) Annual Meeting, and the European Society of Medical Oncology (ESMO) Gynaecological Cancers Congress.
“We are pleased to see multiple presentations at ASCO from our partners, including Jazz Pharmaceuticals, Johnson & Johnson, and Daiichi Sankyo, which further validate our expertise in multispecific and bispecific antibodies, and reinforce our shared commitment to tackling difficult-to-treat cancers,” said Kenneth Galbraith, Chair and Chief Executive Officer at Zymeworks. “In particular, we are looking forward to the outcomes and survival data presentations for zanidatamab in various tumor types, including HER2-positive gastroesophageal cancer, which underscore the potential of our Azymetric™ platform to develop novel therapies for diseases of high unmet medical need.”
ASCO Annual Meeting
Zymeworks and its partners will present multiple abstracts at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31 – June 4, 2025 in Chicago, IL.
Ziihera
| Title | Authors | Presentation Details |
| Long-term outcomes and overall survival for zanidatamab + chemotherapy in HER2-positive advanced or metastatic gastroesophageal adenocarcinoma: 4-year follow-up of a phase 2 trial | Elena Elimova, Jaffer Ajani, Howard Burris, Crystal S. Denlinger, Syma Iqbal, Yoon-Koo Kang, Jwa Hoon Kim, Keun-Wook Lee, Bruce Lin, Rutika Mehta, Do-Youn Oh, Sun Young Rha, Chengzhi Xie, Diana Shpektor, Phillip M. Garfin, Geoffrey Ku | Type: Rapid Oral Abstract Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Date: Monday, June 2, 11:30 am-1:00 pm Central Daylight Time (CDT) Number: 4013 |
| Concordance analysis between tumor tissue HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH) and a translational analysis of plasma ctDNA in patients (pts) with biliary tract cancer (BTC): An exploratory analysis from phase 2 HERIZON-BTC-01 | James J. Harding, Jin Won Kim, Do-Youn Oh, Heung-Moon Chang, Emerson Y. Chen, Dong Uk Kim, Eric Chen, Joon Oh Park, Mohamedtaki A. Tejani, Jean-Phillippe Metges, John A. Bridgewater, Teresa Macarulla, Xiaotian Wu, Yi Zhao, Diana Shpektor, Phillip M. Garfin, Shubham Pant | Type: Poster Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Date: Saturday, May 31, 9:00 am-12:00 pm CDT Number: 4102 |
| Survival outcomes for zanidatamab-hrii compared to chemotherapy in previously treated HER2-positive (IHC3+) biliary tract cancer (BTC): HERIZON-BTC-01 vs a real-world (RW) external control arm (ECA) | Richard Kim, Xiaozhou Fan, Javier Sabater, Wayne Su, Kathleen Hurwitz, Kayla Hendrickson, Kara Bennett, Catherine Wiener, Phillip M. Garfin, Joan Zape, Mark A. Ozog, John A. Bridgewater, Juan W. Valle, Farshid Dayyani | Type: Poster Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Date: Saturday, May 31, 9:00 am-12:00 pm CDT Number: 4101 |
Azymetric™ Platform Partners
| Title | Authors | Presentation Details |
| Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC) | Capucine Baldini, Armelle Vinceneux, Debbie G. Robbrecht, Bernard D. Doger de Spéville, Karen A. Autio, Michael T. Schweizer, Emiliano Calvo, Laura Medina Rodriguez, Marloes V. Dongen. Jean-Laurent Deville, Alice Bernard-Tessier, Debopriya Ghosh, Kristin M. Shotts, Pharavee Jaiprasart, Leanne Cartee, Daria Gaut, Josh D. Lauring, Sherry C. Wang, Victor M. Villalobos, Mark N. Stein | Type: Rapid Oral Abstract Session: Genitourinary Cancer—Prostate, Testicular, and Penile Date: Sunday, June 1, 4:30-6:00 pm CDT Number: 5017 |
| A Phase 1, first-in-human study of D5-2243, an HLA-A*02/NY-ESO-directed bispecific T-cell engager, in patients with advanced solid tumors | Sandra P. D'Angelo, Vivek Subbiah, Jean-Yves Blay, Michael J Wagner, Neeltje Steeghs, Jeonghwan Youk, Hideki Mizusako, Yoshihiro Ohue, Jin Jin, Abdul Waheed Rajper, Nicole Tesar, Patrick Schöffski | Type: Poster Session: Developmental Therapeutics—Immunotherapy Date: Monday, June 2, 1:30-4:30 pm CDT Number: TPS2668 |
ZW171
| Title | Authors | Presentation Details |
| Design of a first-in-human multicenter open-label study of ZW171, a mesothelin x CD3 targeting bispecific T-cell engager, in participants with advanced solid tumors: ZWI-ZW171-101 | Melissa L. Johnson, John T. Hamm, Fiona Thistlethwaite, Myung-Ju Ahn, Erin L. Schenk, Jason J. Luke, Diana L. Hanna, Anna R. Minchom, Byoung Chul Cho, Dong-Wan Kim. Rebecca Kristeleit, Dmitriy Zamarin, Catherine Davidson, Joseph Woolery, Pranshul Chauhan, Martin Wermke | Type: Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Date: Monday, June 2, 1:30 pm-4:30 pm CDT Number: TPS3160 |
ESMO Gynaecological Cancers Congress
Zymeworks will present a TiP poster at the ESMO Gynaecological Cancers Congress, which is taking place June 19-21, 2025 in Vienna, Austria.
| Title | Authors | Presentation Details |
| Design of a First-in-Human Multicenter Open-Label Study of ZW191, a Folate Receptor α–Targeting Antibody-Drug Conjugate Utilizing a Novel TOPO1i Payload, in Participants With Advanced Solid Tumors: ZWI-ZW191-101 | David Sommerhalder, Alexander I. Spira, Tarek Meniawy, Kosei Hasegawa, David Shao Peng Tan, Daniel SW Tan, Byoung-Gie Kim, Joseph Woolery, Syed Raza, Noboru Yamamoto | Type: Poster Date: Friday, June 20, 12:40 pm-1:30 pm Central European Summer Time (CEST) Number: 444 |
“We are pleased to share TiP posters at ASCO and ESMO-Gyn, for ZW171 and ZW191 respectively, which will discuss additional details of our ongoing Phase 1 clinical trials evaluating our novel therapeutic candidates in multiple solid tumors,” said Sabeen Mekan, M.D., Senior Vice President, Clinical Development at Zymeworks. “We are making good progress with global enrollment across diverse patient populations for both trials. This broad enrollment will enable us to develop robust and meaningful analyses, and we look forward to presenting initial data at a future medical meeting.”
About the Azymetric Platform
Azymetric™ is a heterodimeric antibody technology that gives the ability to engineer, screen, and effectively choose the optimal geometry and valency for our targeted treatments. These customized therapeutic antibodies are engineered to simultaneously bind to multiple distinct locations on a target or to multiple targets, resulting in unique mechanisms of action not accessible through typical monospecific antibodies. Azymetric antibodies can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering and internalization, and increase tumor-specific targeting. Zymeworks’ other technologies can combine with Azymetric to engineer the antibody backbone of a bispecific antibody-drug conjugate or the base of a multispecific therapeutic, to potentially overcome known therapeutic barriers and help design potential best-in-class bispecifics and trispecifics.
Clinical validation of the Azymetric platform is demonstrated by the accelerated approval our partner Jazz Pharmaceuticals received from the U.S. Food and Drug Administration in 2024 for Ziihera® (zanidatamab-hrii), a treatment for advanced HER2-positive biliary tract cancer in adults who have received prior therapy.
About ZW171
ZW171 is a bispecific antibody designed to enable T cell-mediated tumor cell killing through simultaneous binding to the extracellular domain of mesothelin (MSLN) protein on tumor cells and the engagement of CD3 on T cells. Moderate to high membranous MSLN expression is frequent in ovarian cancer, non-small cell lung cancer, mesothelioma and other cancers1. Preliminary evidence of anti-tumor activity with engineered T-cell therapy supports utility of T-cell targeted therapies in treatment of MSLN-expressing solid tumors2. ZW171’s unique 2+1 format and incorporation of a novel low-affinity anti-CD3 binder aims to improve the therapeutic window in patients by limiting on-target, off-tumor effects and cytokine release syndrome (CRS) while maintaining potent anti-tumor activity against MSLN-expressing cancers3. By selectively binding to tumors and sparing normal tissues, ZW171 is designed to improve both tolerability and anti-tumor activity against MSLN-expressing cancers. Engineered using our Azymetric™ and EFECT™4 technologies, ZW171 demonstrates enhanced anti-tumor activity and safety in preclinical models, inducing potent, preferential killing of MSLN-overexpressing cells while mitigating the risk of on-target, off-tumor activity, peripheral T cell activation, and CRS.
About ZW191
ZW191 is an antibody-drug conjugate (ADC) that is engineered to target a protein called folate receptor-⍺ (FR⍺) that is found on the surface of a variety of tumors such as on ovarian, endometrial, and lung cancers. ZW191’s differentiated design is built using our novel, bystander active, TOPO1i payload technology, ZD06519; its FRα-targeting monoclonal antibody was selected based on compelling internalization characteristics to enable targeting of high, mid, and low levels of FRα expression. A drug-antibody-ratio (DAR) of eight was selected due to the restricted expression profile of FRα in normal tissues and to enhance our ability to deliver payload to tumors with lower levels of FRα. FRα is a clinically validated target, found in approximately 75% of high-grade serous ovarian carcinomas, 50% of endometrial cancers, and in 70% of non-small cell lung cancer. Preclinical data demonstrate strong ZW191 activity across a range of FRα-expressing patient-derived xenografts, including models with low levels of FRα. The ability to target lower levels of FRα is in part due to the DAR-eight format and the observed superior internalization, payload delivery, and tissue penetration derived from the ZW191 monoclonal antibody compared to other FRα monoclonal antibodies used in ADCs currently or previously in development. In a good laboratory practices toxicology study, ZW191 achieved a highest non-severely toxic dose in non-human primates of 60 mg/kg, which presents a compelling profile and enables the expectation of potentially achieving an efficacious dose level in the Phase 1 clinical trial.
About Ziihera
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo5. In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test5. The U.S. Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)5.
Zanidatamab is not yet approved outside of the United States.
Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer.