ZW251 / Zymeworks - LARVOL DELTA

Zymeworks Provides Corporate Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Based on our encouraging preclinical results and the unique potential opportunity to help hepatocellular carcinoma patients, we have decided to reprioritize resources for the advancement of ZW251, for which an IND submission is now planned for mid-2025. As a result, we have paused preparations for the commencement of Phase 1 studies of ZW220 at this time. However, we believe ZW220 remains a highly differentiated, IND-ready ADC with encouraging preclinical data and strong commercial rationale with partnership potential. We look forward to providing future updates on the development for ZW220....'We look forward to initiating a Phase 1 trial for ZW251 this year'."

IND • New P1 trial • Pipeline update • Hepatocellular Cancer

Zymeworks Outlines Strategic Priorities and Outlook for 2025 and 2026 (GlobeNewswire) - "Investigational new drug (IND) applications for initiating first-in-human studies for ZW220 and ZW251 in solid tumors anticipated in 2025. IND application...for initiating first-in-human studies for ZW209...anticipated in 2026."

IND • Solid Tumor

Zymeworks Hosts R&D Day Highlighting Continued Clinical Progress in Oncology Programs... (GlobeNewswire) - "The Company expects to submit an IND and non-U.S. applications to commence Phase 1 clinical studies for ZW209 in 1H-2026...The Company expects to submit an IND and non-U.S. applications to commence Phase 1 clinical studies for ZW251 in 2H-2025...The Company continues to develop and advance additional solid tumor product candidates beyond the 5 x 5 portfolio, with a specific focus on GI tract cancers, supporting further potential IND applications in 2027 and beyond."

IND • New P1 trial • Hepatocellular Cancer • Oncology

Zymeworks Presents New Preclinical Data on Antibody-Drug Conjugate Programs at EORTC-NCI-AACR Conference (GlobeNewswire) - "Results demonstrate that ZW251 shows promise as a new treatment option for patients, potentially improving upon the current standard of care (SOC). Demonstrating strong anti-tumor activity across a wide range of hepatocellular carcinoma (HCC) models, including those with lower and heterogenous GPC3 expression, ZW251 was designed with a DAR of four, striking a balance between tolerability and broad anti-tumor effectiveness. In NHP studies, ZW251 displayed significant tolerability at doses up to 120 mg/kg."

IND • Preclinical • Hepatocellular Cancer

ZW251, a novel glypican-3-targeting antibody-drug conjugate bearing a topoisomerase I inhibitor payload demonstrates compelling preclinical activity in hepatocellular carcinoma models (EORTC-NCI-AACR 2024) - "Overall, these results support the potential of ZW251 as a novel therapeutic agent against GPC3-bearing cancers including HCC. An IND application is anticipated in 2025."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Zymeworks Presents New Preclinical Data on Antibody-Drug Conjugate Programs at EORTC-NCI-AACR Conference (GlobeNewswire) - "Results demonstrate that ZW220 has the potential for improvement over previous NaPi2b ADCs and on the basis of efficacy, tolerability and payload mechanism.... We believe it offers a differentiated safety profile compared to other ADCs currently in the clinic, demonstrating high tolerability in animal studies with MTD ≥90 mg/kg in non-human primates (NHP) and ≥200 mg/kg in rats, suggesting potential for high doses in humans. The low drug-antibody ratio (DAR) and moderate stability of the antibody-linker provide a good balance of stability, tolerability, and anti-tumor activity, while potentially minimizing antibody-driven toxicities....Presentations highlight key preclinical data that support investigational new drug application (IND) submissions for ZW220 in 1H and ZW251 in 2H in 2025."

IND • Preclinical • Non Small Cell Lung Cancer • Ovarian Cancer • Uterine Cancer

Zymeworks to Present Preclinical Data on Antibody-Drug Conjugate Programs at EORTC-NCI-AACR Conference (GlobeNewswire) - "Zymeworks Inc...announced two presentations highlighting results from recent preclinical research for Zymeworks’ antibody-drug conjugate candidates ZW220 and ZW251. Results will be presented at the European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) Conference in Barcelona being held October 23-25, 2024....'We are encouraged by the progress of these next-generation ADC programs, which remain on track for IND filings in 2025..."

IND • Preclinical • Gastrointestinal Cancer • Gynecologic Cancers • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer

Zymeworks Provides Corporate Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "By reallocating our resources, we can focus on accelerating the progression of ZW171 and ZW191 into the dose escalation stage of the respective Phase 1 clinical trials, as well as the planned IND filings for ZW220 and ZW251 in 2025."

IND • New P1 trial • Oncology

Zymeworks Reports Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "Zanidatamab zovodotin (ZW49) remains ready for a Phase 2 clinical trial, in combination with pembrolizumab, with the recommended Phase 2 dose of 2.5 mg/kg every three weeks. However, the initiation of the planned Phase 2 study has been deprioritized, pending more clarity from the evolving clinical landscape....We remain on track to accomplish our goal of submitting IND or foreign equivalent submissions in 2024 for both ZW191 and ZW171, in 2025 for ZW220 and ZW251, and to nominate our fifth IND candidate during 2024, with a planned IND filing in 1H 2026."

IND • New P2 trial • Regulatory • Oncology

Zymeworks Provides Corporate Update and Reports Third Quarter 2023 Financial Results (GlobeNewswire) - "Termination of Licensing Agreement for Zanidatamab Zovodotin with BeiGene...We anticipate filing an IND in the second half of 2025 for ZW251, a potential first-in-class ADC molecule designed for the treatment of GPC3-expressing hepatocellular carcinoma (HCC)....'The progression of ZW251 marks the next step in our '5 by 5' strategy, serving as the fourth novel medicine nominated for clinical development, joining ZW191 and ZW171, both expected for initiation of clinical studies in 2024, and ZW220, expected for initiation of clinical development in the first half of 2025'..."

IND • Licensing / partnership • New trial • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Introducing ZW251, a Novel Glypican 3-Targeting Antibody Drug Conjugate Bearing a Topoisomerase 1 Inhibitor Payload (ADC-USA 2023) - "Describing Glypican-3, which is a prevalent and selective marker for hepatocellular carcinoma (HCC); Explaining the design features making ZW251 well suited to target GPC3-expressing HCC; Highlighting the preclinical characterization of ZW251 including anti-tumor activity, PK, and non-human primate toxicology"

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

ZW251, a novel glypican-3-targeting antibody drug conjugate bearing a topoisomerase 1 inhibitor payload (AACR 2023) - "The ZW251 antibody backbone demonstrated nanomolar binding affinity to both human and cynomolgus monkey GPC3, and strong binding to target-expressing cancer cell lines. Rapid internalization of ZW251 antibody was observed in GPC3-expressing HCC cell lines. ZW251 exhibited potent and target-specific cytotoxicity in a panel of HCC cells cultured either in monolayer or as 3D spheroids."

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Zymeworks Presents New Data from Multiple Preclinical and Clinical Development Programs at the 2023 American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Zymeworks...announced 11 presentations including new data from its clinical and preclinical development-stage programs at the 2023 American Association for Cancer Research (AACR) Annual Meeting....ZW251 exhibited robust anti-tumor activity in a large panel of HCC cell line-derived xenograft (CDX) and PDX models at both DAR 4 and DAR 8. Anti-tumor activity (tumor growth inhibition > 50%) for ZW251 was evident in 82% of models with GPC3 H-score > 200 and 50-75% of models with GPC3 H-score < 200, providing evidence of ZW251’s potential activity in a range of GPC3-expression levels.'"

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor