zanidatamab zovodotin (ZW49) / Zymeworks, BeiGene - LARVOL DELTA

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "Advan-TIG-302 (TIGIT antibody): anticipate interim data readout from Phase 3 study in first-line PD(L)1-high non small cell lung cancer in the second half of 2025...BGB-43395 (CDK4 inhibitor): continued dose escalation in monotherapy and in combination with fulvestrant and letrozole in the anticipated efficacious dose range; more than 180 patients enrolled to date and proof-of-concept expected in the first half of 2025...Zanidatamab (HER2 bispecific antibody) in combination with tislelizumab and chemotherapy: anticipate primary PFS data readout from Phase 3 study in first-line HER2-positive gastroesophageal adenocarcinoma in the second half of 2025...BGB-45035 (IRAK4 CDAC): currently in dose escalation in both SAD and MAD cohorts with more than 130 subjects enrolled...Phase 2 study planned in 2025; proof-of-concept for tissue IRAK4 degradation in the second half of 2025."

Clinical data • New P2 trial • Breast Cancer • Gastroesophageal Cancer • Immunology • Non Small Cell Lung Cancer

A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers (clinicaltrials.gov) - P1 | N=112 | Completed | Sponsor: Zymeworks BC Inc. | N=174 ➔ 112 | Trial completion date: Aug 2025 ➔ Oct 2024 | Trial primary completion date: Aug 2025 ➔ Sep 2024 | Active, not recruiting ➔ Completed

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • Oncology • HER-2

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Biliary Tract Cancers, Version 5.2024. (NCCN)

NCCN guideline • Biliary Tract Cancer

Zymeworks Provides Corporate Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Following a strategic review of our emerging wholly-owned pipeline, we decided to formally discontinue the clinical development program of our HER2-targeted antibody-drug conjugate, zanidatamab zovodotin...This decision aligns with our commitment to focus on the development of our early-stage programs, which we believe have the potential to be best-in-class and/or first-in-class drugs...We believe zanidatamab zovodotin remains a promising Phase 2 ready asset, and we continue to explore partnering discussions where zanidatamab zovodotin may provide complementary coverage to a pipeline for NSCLC, breast cancer and other indications....During the six months ended June 30, 2024, we recorded a non-cash impairment charge of $17.3 million as a result of our decision to discontinue the zanidatamab zovodotin clinical development program which utilized the technology represented by acquired in-process research and development assets."

Commercial • Discontinued • Breast Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Oncology • 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 Outlines Strategic Priorities and Outlook for 2024 and 2025 (GlobeNewswire) - "Zymeworks Inc...provided an update on key strategic priorities for 2024 and 2025...Regained full development rights for zanidatamab zovodotin (ZW49) with plans to conduct a Phase 2 study in NSCLC in 2024."

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers (clinicaltrials.gov) - P1 | N=174 | Active, not recruiting | Sponsor: Zymeworks Inc. | Trial primary completion date: Aug 2023 ➔ Aug 2025

Metastases • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • HER-2

Phase 1 Study of Zanidatamab Zovodotin (ZW49): Safety Profile and Recommended Dose (RD) in Patients with Human Epidermal Growth Factor2 (HER2)-positive Solid Cancers. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • P1 data • Oncology • Solid Tumor • HER-2

A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers (clinicaltrials.gov) - P1 | N=174 | Active, not recruiting | Sponsor: Zymeworks Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Preliminary results from a phase I study using the bispecific, human epidermal growth factor 2 (HER2)-targeting antibody-drug conjugate (ADC) zanidatamab zovodotin (ZW49) in solid cancers (ESMO 2022) - P1 | "Conclusions ZW49 has a manageable safety profile with encouraging single-agent antitumor activity in heavily pretreated pts with HER2+ cancers. Enrollment continues at 1.75 mg/kg QW in DE and 1.5 mg/kg QW in DX."

P1 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Zymeworks Provides Corporate Update and Reports First Quarter 2023 Financial Results (GlobeNewswire) - "Zanidatamab Zovodotin (zani zo) Preclinical Data Presented at AACR:...These data provided the mechanistic rationale for zani zo to be combined with an anti-PD-1 therapy, showing that zani zo induces hallmarks of immunogenic cell death, which when combined with an anti-PD-1 checkpoint inhibitor may show a mechanistic advantage when used as a combination therapy."

Preclinical • Oncology

Zanidatamab zovodotin (ZW49) induces hallmarks of immunogenic cell death and is active in patient-derived xenograft models of gastric cancer (AACR 2023) - P1 | "Anti-tumor activity was observed in 5/7 (71%) PDX models of gastric cancer after a single i.v. dose of 6 mg/kg, including in models with moderate and weak HER2 expression. The strong anti-tumor activity of ZW-49 in vivo, together with its ability to induce ICD and potential adaptive immune responses, support ZW49 as a promising ADC for the treatment of HER2-expressing cancers warranting further investigation, including potential combination with checkpoint inhibitors."

Immunogenic cell death • Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CALR • HMGB1

Zymeworks Reports Fourth Quarter and Full Year 2022 Financial Results (Businesswire) - "Zymeworks had 11 abstracts accepted for presentation at the 2023 American Association for Cancer Research (AACR) meeting taking place April 14-19 in Orlando, Florida. We look forward to sharing additional information on our preclinical product candidates and zanidatamab zovodotin....Additionally, during 2023 we expect to nominate an additional preclinical product candidate with a goal of an expected IND filing by 2025; Zanidatamab Zovodotin (ZW49) to Progress in Phase 2 Clinical Trial: With the announcement of the recommended Phase 2 dose (RP2D) of 2.5 mg/kg every three weeks, development of zanidatamab zovodotin continues with multiple Phase 2 studies expected to commence enrollment in 2023."

New molecule • New P2 trial • Preclinical • Oncology

A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers (clinicaltrials.gov) - P1; N=174; Recruiting; Sponsor: Zymeworks Inc.; Trial completion date: Apr 2023 ➔ Aug 2025; Trial primary completion date: May 2021 ➔ Aug 2023

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

"Hope $ZYME plan to layer a PD-1 on top of ZW49 in any post-ENHERTU patient segment (?) Even then, that dose-limiting ocular tox!" (@ablT315I)

Clinical • PD-1

"Ken Galbraith ( $ZYME CEO as of 10mths ago) highlighting ZW49. Says he's convinced it has a place behind Kadcyla & Enhertu, and lies outside the $JAZZ deal #Jefferies22" (@JacobPlieth)

"Zymeworks ($ZYME) ZW49 zanidatamab anti-biparatopic Her2+zovodotin auristatin against HER2+ breast and gastric cancers https://t.co/2x8eP11zTN #ESMO22" (@char1eylu)

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Zymeworks Reports Preliminary Phase 1 Trial Results for Zanidatamab Zovodotin (ZW49) at European Society for Medical Oncology Annual Congress (Businesswire) - P1 | N=77 | NCT03821233 | Sponsor: Zymeworks | "The patients represented a variety of HER2-expressing cancers including breast, gastroesophageal, ovarian, endometrial, bladder, biliary tract, anal, colorectal, pancreatic and lung. At the time of the analysis, the maximum tolerated dose had not yet been reached....In the trial, zanidatamab zovodotin was shown to have a manageable safety profile with the majority of adverse events being Grade 1 or 2 in severity. In patients with HER2-positive cancers treated with zanidatamab zovodotin at 2.5 mg/kg Q3W (dose escalation + dose expansion), the confirmed objective response rate was 31% and the disease control rate was 72%."

P1 data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Zymeworks Announces Release of ESMO Abstract for Phase 1 Study of Zanidatamab Zovodotin (ZW49) in Solid Cancers (Businesswire) - P1 | N=174 | NCT03821233 | Sponsor: Zymeworks Inc. | "Zymeworks...announced the release of an abstract by ESMO with preliminary results from the company’s Phase 1 study of zanidatamab zovodotin (ZW49), an investigational novel bispecific HER2 targeted antibody-drug conjugate....Among seven patients who experienced TRAEs of grade 3 or higher, two were grade 4 events including infusion-related reaction and decreased neutrophil count....Results also showed encouraging single-agent anti-tumor activity in heavily pretreated patients with HER2+ cancers, including a confirmed objective response rate of 28% and a disease control rate of 72% in 29 patients treated at a dose of 2.5 mg/kg on an every three week (Q3W) schedule."

P1 data • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Zymeworks Announces Oral Presentation of Data from Phase 1 Study of Zanidatamab Zovodotin (ZW49) in Solid Cancers at European Society for Medical Oncology (ESMO) Congress 2022 in Paris (Businesswire) - "Zymeworks...announced that data from the company’s Phase 1 study of zanidatamab zovodotin (ZW49), an investigational novel bispecific HER2 targeted antibody-drug conjugate, were accepted for an oral presentation at the European Society for Medical Oncology Congress 2022 in Paris. The abstract...will be presented by Komal Jhaveri, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center in NYC, in a mini-oral presentation on Monday, September 12 at 5:25 pm CEST during the ESMO meeting being held September 9-13, 2022, at the Paris Expo Porte de Versailles in Paris, France."

P1 data • Oncology • Solid Tumor

Zymeworks Reports 2021 Third Quarter Financial Results (Businesswire) - "ZW49 Program Update: The ZW49 program continues to advance in the weekly and once every three week dosing schedules. Expansion cohorts evaluating 2.5 mg/kg every three weeks have enrolled 29 patients and are expected to complete enrollment (30 patients) prior to year end. In parallel, the weekly dose regimen has enrolled 14 patients and continues to dose escalate as the maximum tolerable dose has not been reached. No dose-limiting toxicities have been observed to date. The results of these studies will inform the recommended Phase 2 dose and schedule with safety and efficacy data expected to be presented at a medical conference in 2022."

Enrollment status • P1 data • Trial status • Oncology

Zymeworks Reports 2021 Second Quarter Financial Results (Businesswire) - "Second Quarter 2021 Business Highlights and Recent Developments: Zymeworks has opened new sites in South Korea and Australia to accelerate the cohort expansion portion of the Phase 1 clinical trial for ZW49. This will support Zymeworks' goal of identifying the recommended Phase 2 dose and schedule by the end of this year. Dose escalation continues in weekly and once every three week schedules while three indication-specific expansion cohorts utilizing the 2.5 mg/kg once every three week regimen are ongoing."

Trial status • Oncology

Zymeworks Advances HER2 Bispecific Antibody-Drug Conjugate, ZW49, into Expansion Cohort Stage of Clinical Development (Businesswire) - "Zymeworks...announced today that the Company has begun enrolling patients into the expansion cohort portion of the ongoing Phase 1 clinical trial for ZW49, its novel HER2-targeted antibody-drug conjugate (ADC)."

Trial status • Oncology • Solid Tumor

ZW49, a HER2-targeted biparatopic antibody-drug conjugate for the treatment of HER2-expressing cancers (AACR 2018) - "...Multiple antibody-drug conjugate (ADC) technologies are being explored in this setting, some of which utilize the anti-HER2 antibody trastuzumab...In cellular binding assays, it was confirmed that the payload conjugation to ZW25 did not affect the antibodys binding to HER2-expressing cells...In nonhuman primates ZW49 administered intravenously every two weeks for three doses was well tolerated. Based on these findings, we are proceeding with further development of ZW49 as a therapeutic candidate in HER2-expressing cancers."

Gastric Cancer