ZW191 / Zymeworks - LARVOL DELTA

Design and development of biparatopic antibody-drug conjugates against protein tyrosine kinase 7 (AACR 2025) - P1 | "ADCs were produced by conjugating the top biparatopic and monoparatopic antibodies to ZD06519, a topoisomerase 1 inhibitor payload used in ZW191, an ADC targeting FRα under evaluation in a phase 1 clinical trial (NCT06555744). Across multiple cancer cell lines with varying PTK7 expression we compared a lead monoparatopic antibody and cofetuzumab with the top biparatopic antibody which demonstrated greater cell surface decoration and better internalization. At clinically relevant doses, the biparatopic ZD06519 ADC was more efficacious than cofetuzumab pelidotin in triple negative breast cancer and lung cancer cell line derived xenograft models. Additional studies of the PTK7 biparatopic ADC in patient-derived xenograft models and a non-human primate tolerability study are planned."

Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • PTK7

ZW191: Data from P1 trial (NCT06555744) for solid tumors in H2 2025 (Zymeworks) - Research & Development Day

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Zymeworks Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating ZW191 in Folate Receptor-⍺ Expressing Advanced Solid Tumors (GlobeNewswire) - "Zymeworks...announced that the first patient has been dosed in the company’s first-in-human Phase 1 trial (NCT06555744) to evaluate the safety and tolerability of the investigational therapy ZW191 in the treatment of advanced folate receptor-⍺ (FR⍺)-expressing solid tumors including ovarian, endometrial, and non-small cell lung (NSCLC) cancers....The Phase 1 trial is a two-part, multi-center, global study that aims to enroll 145 adult patients with advanced FR⍺-expressing cancers. The Company expects to enroll patients at investigator sites in North America, Europe, and the Asia-Pacific region."

Trial status • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

A Study of ZW191 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=145 | Recruiting | Sponsor: Zymeworks BC Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

A Study of ZW191 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=145 | Not yet recruiting | Sponsor: Zymeworks BC Inc.

Metastases • New P1 trial • Oncology • 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

Zymeworks Announces FDA Clearance of Investigational New Drug Application for ZW191, a Novel Folate Receptor-⍺ Targeted Topoisomerase I Inhibitor Antibody-Drug Conjugate (GlobeNewswire) - "Zymeworks...announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ZW191, the Company’s novel folate receptor-⍺ (FR⍺) targeted topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate (ADC)....ZW191 was designed using the Company’s drug conjugate platforms, including the novel TOPO1i-based payload technology, ZD06519, to target FR⍺-expressing tumors including ovarian and other gynecological cancers, as well as non-small cell lung cancer (NSCLC)....The Company expects to file applications seeking regulatory authorization to initiate clinical studies for ZW191 in non-US jurisdictions in the second half of 2024."

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

ZW191: “ZW191 displays favorable PK and is well tolerated in NHP at exposure levels above those projected to be efficacious”; Solid tumors (Zymeworks) - Corporate Presentation

Preclinical • Oncology • Solid Tumor

ZW191 - a FRα-targeting antibody drug conjugate with strong preclinical activity across multiple FRα-expressing indications (AACR 2024) - "The antibody component of ZW191 features a favorable binding profile with strong binding to FRα, and drives superior tumor spheroid penetration, cellular internalization, and payload delivery compared to FRα targeted antibodies used in multiple other ADCs. ZW191 demonstrates potent activity in FRα expressing cell cultures and effective bystander activity. In a panel of PDX models representing a range of FRα expression, ZW191 demonstrates compelling anti-tumor activity across ovarian and endometrial cancers, NSCLC and TNBC."

Preclinical • Colorectal Cancer • Endometrial Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1

Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024 American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Abstract: 1862:...The compelling preclinical activity profile supports ZW191 development across multiple tumor types, including FRα-high/mid/low ovarian cancers and other FRα-expressing indications, including non-small cell lung cancer, endometrial cancer, and triple-negative breast cancer. An investigational new drug (IND) submission or foreign equivalent is planned for 2024....Key results: Superior internalization, payload delivery, and spheroid penetration to other FRα-targeted multi-specific antibodies. Bystander active payload drives activity in settings with heterogeneous FRα expression."

IND • Preclinical • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

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 to Present Preclinical Data on Antibody-Drug Conjugate and Multispecific Platforms at the American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Zymeworks Inc...today announced acceptance of five abstracts for poster presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting taking place at the San Diego Convention Center in San Diego, CA from April 5-10, 2024."

Preclinical • Oncology • Solid Tumor

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

ZW191, a novel FRa-targeting antibody drug conjugate bearing a topoisomerase 1 inhibitor payload (AACR 2023) - "The antibody component of ZW191 features a favorable binding profile with strong and exclusive binding to FRa, and drives superior tumor spheroid penetration, cellular internalization, and payload delivery compared to FRa targeted antibodies used in other ADCs. ZW191 demonstrates potent activity in FRa expressing 3D tumor spheroid cultures and effective bystander activity. In a panel of CDX and PDX models representing a range of FRa expression, ZW191 demonstrates compelling anti-tumor activity at exposures that are estimated to be readily achievable in the clinic."

Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

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....ZW191 exhibited a compelling preclinical activity profile that supports potential activity in targeting FRα-high/mid/low ovarian cancers. ZW191 demonstrated strong responses in FRα-low expressing PDX models, indicating potential activity in other oncology indications with lower levels of FRα."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • 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

ZW191 – A FRa-Targeted ADC Employing Zymework’s TOPO1-Inhibitor Platform (ADC London 2023) - "Synopsis ZW191 integrates a highly effective FRa-targeting antibody with Zymework’s novel camptothecin-based TOPO1 inhibitor platform Overview of preclinical studies demonstrating ZW191’s favorable activity and tolerability profiles Discussing the potential for a differentiated ADC to deepen and expand responses in patients with tumors expressing a range of FRa levels"

Oncology