ZW191 / Zymeworks - LARVOL DELTA

ZW191: “ZW191 has been safely administered during dose escalation up to 11.2 mg/kg, with the majority of participants still on treatment”; Solid tumor (Zymeworks) - Initial Results from the Phase 1 Trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺: “ORRs (uPR + cPR) between 6.4 mg/kg to 9.6 mg/kg were: 53% (overall) and 64% (GYN cancers)”

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

Clinical Highlights: ZW191… (GlobeNewswire) - "Dose optimization to further evaluate safety and efficacy at 6.4 mg/kg and 9.6 mg/kg in ovarian cancer is expected to initiate in 4Q-2025."

Trial status • Ovarian Cancer

Preliminary results from a phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α–targeting antibody-drug conjugate, in patients with advanced solid tumors (AACR-NCI-EORTC 2025) - P1 | "ZW191 has been safely administered during dose escalation up to 9.6 mg/kg and has demonstrated preliminary efficacy across multiple dose levels, starting at 3.2mg/kg Q3W. Part 1 dose escalation is ongoing."

Clinical • First-in-human • Late-breaking abstract • Metastases • P1 data • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Zymeworks Presents Initial Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺ at AACR-NCI-EORTC Conference (GlobeNewswire) - "Preliminary efficacy data, combined with a tolerable safety profile, reinforce the potential of ZW191 in patients with advanced solid tumors, including ovarian, endometrial, and non-small cell lung cancer. 64% overall response rate in gynecological cancers at doses ≥6.4mg/kg. Responses observed at all doses evaluated at 3.2mg/kg....Dose optimization of ZW191 in ovarian cancer to initiate in 4Q-2025."

P1 data • Trial status • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

A Phase 1 study for ZW191 is actively recruiting and ZW251 is expected to enter clinical trials in 2025. (GlobeNewswire)

Trial status • Hepatocellular Cancer • Solid Tumor

Zymeworks to Present Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺, at AACR-NCI-EORTC International Conference (GlobeNewswire) - "Preliminary data presented at the AACR-NCI-EORTC conference will provide insights into the potential of ZW191 in patients with advanced solid tumors, including ovarian cancer, endometrial cancer, and non-small cell lung cancer."

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

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

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 ZW191, a folate receptor a-targeting antibody-drug conjugate utilizing a novel TOPO1i payload, in participants with advanced solid tumors: ZWI-ZW191-101 (ESMO-GC 2025) - P1 | "This study is sponsored by Zymeworks. Legal entity responsible for the study Zymeworks Inc."

Clinical • Metastases • P1 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

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 also be presenting a trial-in-progress poster at the ESMO Gynaecological Cancers Congress annual meeting on the ongoing first-in-human Phase 1 study for ZW191 (ZWI-ZW191-101): Title: 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 (Poster Board: 125TiP)....Date and Time: June 20, 2025 at 12:40 PM – 13:30 PM CEST."

Clinical protocol • Solid Tumor

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