ZW171 / Zymeworks - LARVOL DELTA

ZWI-ZW171-10: A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers (clinicaltrials.gov) - P1 | N=32 | Terminated | Sponsor: Zymeworks BC Inc. | N=160 ➔ 32 | Trial completion date: Dec 2027 ➔ Oct 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2027 ➔ Sep 2025; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Zymeworks Announces Decision to Discontinue Clinical Development of ZW171, a Mesothelin-directed T cell Engager (The Manila Times) - "The decision to discontinue clinical development of ZW171 was based on completion of the planned cohorts of the dose escalation portion of the Phase 1 trial of ZW171 in patients with ovarian cancer and non-small cell lung cancer....'We continue to advance our broader product pipeline, including the ongoing Phase 1 trial of ZW191 and the initiation of a Phase 1 study for ZW251 expected in 2025. We are also preparing an IND filing for ZW209, our DLL3-directed trispecific T cell engager, planned in the first half of 2026'."

Discontinued • IND • New P1 trial • Non Small Cell Lung Cancer • Ovarian Cancer

ZWI-ZW171-10: A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers (clinicaltrials.gov) - P1 | N=160 | Active, not recruiting | Sponsor: Zymeworks BC Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

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. (ASCO 2025) - P1 | "This is a global study with sites in North America, Europe, and Asia; and actively enrolling participants into Part 1. Clinical trial information: NCT06523803."

Clinical • Metastases • P1 data • Hepatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD3E • MSLN

Zymeworks Announces Presentations Highlighting Breadth of Oncology Portfolio at Upcoming Medical Conferences (GlobeNewswire) - "Zymeworks...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....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."

Clinical data • Trial status • Gastroesophageal Cancer • Gynecologic Cancers

Zymeworks Provides Corporate Update and Reports First Quarter 2025 Financial Results (GlobeNewswire) - "We will be presenting a trial-in-progress poster at the American Society of Clinical Oncology annual meeting on the ongoing first-in-human Phase 1 study for ZW171 (ZWI-ZW171-101): Title: 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 (Poster Board: 473b)....Date and Time: June 2, 2025 at 13:30 PM – 16:30 PM CDT."

Clinical protocol • Solid Tumor

ZW171, a differentiated 2+1 T cell-engaging bispecific antibody with antitumor activity in a range of mesothelin-expressing cancers (AACR 2025) - P1 | "We previously showed that the unique geometry and 2+1 design of ZW171 facilitates tumor selective binding and potent preferential killing of MSLN-mid and -high target cells, while sparing MSLN-low expressing target cells, and enhanced antitumor activity compared to other 2+1 TCE formats and the clinical benchmark HPN536 in MSLN-expressing PBMC-engrafted CDX models. To address the evolving clinical landscape and assess antitumor activity in additional indications and more translationally relevant models, we assessed ZW171 activity in advanced patient-derived organoid and xenograft models and benchmarked to other MSLN-targeting TCE including AMG 305, JNJ-79032421 and CT95...Overall, ZW171 demonstrates differentiated and potent antitumor activity in a range of MSLN-expressing cancers. ZW171 is being evaluated in a Phase 1 clinical trial in MSLN-expressing solid tumors (NCT06523803)."

Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • MSLN

ZW171, a differentiated 2+1 T cell-engaging bispecific antibody with antitumor activity in a range of mesothelin expressing cancers (GlobeNewswire) - "ZW171 demonstrates cytolytic activity across a range of MSLN expressing tumor types including lung, ovarian and pancreatic cancers with anti-tumor activity correlating with MSLN cell surface expression and not related to soluble MSLN levels; ZW171 exhibits strong anti-tumor activity in patient derived xenograft (PDX) models of NSCLC and pancreatic cancer, and in ex-vivo patient-derived ovarian cancer organoids with endogenous tumor-infiltrating lymphocytes (TIL); Relative to other MSLN targeted T cell engagers in development, ZW171 exhibits reduced T cell binding but enhanced cytolytic activity; These data reinforce the differentiated profile of ZW171 and demonstrate its enhanced anti-tumor activity compared to other MSLN-targeting bispecifics."

Preclinical • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer

Mechanistic QSP modeling and translational strategy for determining an FIH dose for ZW171, a bispecific 2+1 T-cell engager molecule targeting mesothelin and CD3 (SITC 2024) - "Conclusions A fit-for-purpose QSP model was developed for ZW171 to facilitate the determination of starting dose in the first-in-human (FIH) clinical study. This approach led to greater confidence in determining the starting dose for the ZW171 Phase 1 clinical study, expected to commence in the second half of 2024."

Oncology • MSLN

Zymeworks Presents Preclinical Data on ZW171 at the Society for Immunotherapy of Cancer (SITC) Conference (Zymeworks Press Release) - "Key highlights: i) A MABEL approach is commonly used to select the starting dose for bispecific CD3 T-cell engagers in first-in-human (FIH) studies based on the most sensitive in vitro assay, potentially leading to selection of a sub-optimal dose. ii) The fit-for-purpose QSP model for ZW171 was established to integrate physiological information (e.g., T cells, MSLN+ cells, CD3/MSLN expression, receptor dynamics), in vitro cytotoxicity data, and preclinical PK data. iii) Unlike traditional MABEL, which relies solely on in vitro data, the QSP-based MABEL approach characterizes the complex interplay between ZW171 and its target antigens."

Preclinical • Oncology • Solid Tumor

Zymeworks Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating ZW171 in Advanced Mesothelin-Expressing Cancers (GlobeNewswire) - "Zymeworks...announced that the first patient has been dosed in the first-in-human Phase 1 trial (NCT06523803) to evaluate the safety and tolerability of the investigational therapy ZW171 in the treatment of advanced or metastatic ovarian cancer, NSCLC, and other MSLN-expressing cancers....The Phase 1 study is a two-part, open-label multi-center study that is expected to enroll approximately 160 adult patients with advanced MSLN-expressing cancers."

Trial status • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor

ZWI-ZW171-10: A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: Zymeworks BC Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers (clinicaltrials.gov) - P1 | N=160 | Not yet recruiting | Sponsor: Zymeworks BC Inc.

Metastases • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Zymeworks Announces FDA Clearance of Investigational New Drug Application for ZW171, a novel 2+1 T-cell Targeting Bispecific Antibody for Mesothelin-expressing Cancers (GlobeNewswire) - "Zymeworks Inc...today announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ZW171, a novel 2+1 T-cell targeting bispecific antibody for mesothelin (MSLN)-expressing cancers....We look forward to initiating clinical development of ZW171 during 2024 and continuing to advance additional product candidates in our ‘5 by 5’ strategy over the next 24 months....The Company expects to file applications seeking regulatory permission to commence clinical studies for ZW171 in other non-US jurisdictions in the second half of 2024."

IND • New trial • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

Zymeworks Announces $50 Million Private Placement to EcoR1 Capital (GlobeNewswire) - "The proceeds from this transaction will help to broaden and potentially accelerate the Company’s ‘5 by 5’ research and development strategy, with investigational new drug application filings for ZW171 and ZW191 scheduled for 2024, as well as for use in funding general corporate purposes."

Financing • Oncology

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

Engineering and Preclinical Development of ZW171: A 2+1 Format Anti-MSLN T Cell Engager (PEGS 2023) - "By tuning affinity and format, we achieved a molecule with potent MSLN-specific activity both in vitro and in vivo, with minimal MSLN-independent T cell binding and activation. Development data suggest that ZW171 has the potential to be an efficacious and safe therapeutic for the treatment of MSLN-expressing cancers."

Preclinical • Oncology • MSLN

ZW171, a T cell-engaging, bispecific antibody for the treatment of mesothelin-expressing solid tumors (AACR 2023) - "Importantly, ZW171 exhibited potent tumor growth inhibition in multiple established tumor models. Collectively, these data suggest that ZW171 has the potential to be an efficacious and safe therapeutic for the treatment of MSLN-expressing cancers."

Hematological Malignancies • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • MSLN

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....ZW171 exhibited potent tumor growth inhibition in MSLN-expressing tumor models and was well tolerated in cynomolgus monkeys up to a single dose of 30 mg/kg. Data suggest that ZW171 could overcome the issues impeding the success of other TCEs developed to treat solid tumors and provide the therapeutic rationale to support the development of ZW171 for the treatment of MLSN-expressing tumors."

Preclinical • Oncology • Solid Tumor

Zymeworks to Present Updated Data on Multiple Product Candidates at the American Association for Cancer Research (AACR) Annual Meeting (Businesswire) - "Zymeworks...announced the acceptance of eleven abstracts for poster presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting....'During the meeting we look forward to sharing new preclinical data on our anticipated 2024 IND candidates, ZW171 and ZW191, as well as other programs that represent potential future therapeutic opportunities and areas of interest'."

Preclinical • Oncology

Zymeworks Provides Corporate Update on Key Strategic Priorities and Outlook for 2023 (Businesswire) - "Selected and advanced two new preclinical product candidates (ZW191 and ZW171), that leverage Zymeworks’ novel, therapeutic technology platforms, with planned Investigational New Drug (IND) applications for both candidates in 2024..."

IND • Oncology • Solid Tumor