ZW220 / Zymeworks - LARVOL DELTA

Therapeutic Applications and Target Strategies of Antibody-Drug Conjugates in Ovarian Cancer. (PubMed, Iran J Pharm Res) - "This review summarizes a range of ADCs targeting tumor-associated antigens in ovarian cancer, including mirvetuximab soravtansine (MIRV), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), sacituzumab tirumotecan (SKB-264), PF-06664178, anetumab ravtansine (BAY 94-9343), BMS-986148, DMOT4039A, RC88, lifastuzumab vedotin (DNIB0600A), upifitamab rilsodotin (ABBV-181), ZW220, DMUC4064A, and sofituzumab vedotin (DMUC5754A). The ADCs hold significant potential to reshape the treatment landscape for ovarian cancer by providing targeted therapeutic options. Further research is required to optimize patient selection, address resistance mechanisms, and improve safety profiles."

Journal • Review • Oncology • Ovarian Cancer • Solid Tumor • MUC4

Zymeworks Provides Corporate Update and Reports Second Quarter 2025 Financial Results (GlobeNewswire) - "R&D expenses were $34.4 million in 2Q-2025 compared to $29.2 million in 2Q-2024, primarily due to an increase in expenses for ZW171, ZW191 and other preclinical expenses related to IND-enabling studies for ZW209 and ZW251. These were partially offset by a decrease in expenses for zanidatamab zovodotin and ZW220."

Commercial • Oncology

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 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

ZW220, a NaPi2b-directed topoisomerase I inhibitor Antibody-Drug Conjugate, demonstrates compelling preclinical activity in NSCLC, ovarian and uterine cancer models, with a favorable toxicology profile in non-human primates (EORTC-NCI-AACR 2024) - "Taken together, the results support the therapeutic potential of ZW220 as a novel ADC which may help address unmet medical need in patients with NaPi2b-expressing tumors. An IND application is anticipated in 2025."

Preclinical • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Kidney Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Uterine Cancer • SLC34A2

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 ZW220, a Novel NaPi2b-Targeting Antibody Drug Conjugate Bearing a Topoisomerase 1 Inhibitor Payload (ADC-USA 2023) - "Describing NaPi2b, which is a clinically validated ADC target in ovarian cancer with good potential in NSCLC and other solid tumors; Exploring the design features making ZW220 well suited to target NaPi2b-expressing tumors; Outlining the characterization of ZW220 including anti-tumor activity, PK, and non-human primate toxicology"

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Zymeworks Provides Corporate Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "...'ZW171 and ZW191 currently remain on track for anticipated IND filings in 2024, and we have nominated an additional preclinical development candidate, ZW220, with an expected IND filing in the first half of 2025'."

IND • New molecule • Oncology • Solid Tumor

ZW220, a novel NaPi2b-targeting antibody drug conjugate bearing a topoisomerase 1 inhibitor payload (AACR 2023) - "ZW220 antibody exhibited cross-reactivity to human and cynomolgus monkey NaPi2b, nanomolar binding affinity and rapid internalization in NaPi2b-expressing cell lines in vitro. ZW220 elicited target-specific, sub-nanomolar cytotoxicity in two-dimensional monolayer and three-dimensional tumor spheroid models and demonstrated bystander-mediated cell killing in cancer cell co-culture assays. The treatment of a panel of ovarian PDXs with a single dose of 6 mg/kg of ZW220 resulted in robust tumor growth inhibition."

Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2