ZW209 / Zymeworks - LARVOL DELTA

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

ZW209, a DLL3 targeted trispecific T cell engager with integrated CD28 co-stimulation, demonstrates safety and potent preclinical efficacy in models of small cell lung cancer (AACR 2025) - "Bispecific T cell engagers (TCE) targeting DLL3, including tarlatamab which has received accelerated approval, have demonstrated anti-tumor activity in the clinic with an improved duration of response compared to current standard of care, including chemotherapy and immunotherapy. Importantly, a ZW209 cynomolgus cross-reactive surrogate molecule displayed a favorable safety profile as it was well tolerated in non-human primates with repeat dosing at 10 mg/kg with no abnormal clinical signs.In summary, these preclinical data support that ZW209 promotes improved anti-tumor activity against DLL3-positive cancer cells relative to competitor bispecific TCEs. By integrating CD28 co-stimulation into our trispecific T cell engager, ZW209 has the potential to improve the rate and duration of response for better clinical outcomes."

Preclinical • Trispecific • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

ZW209, a DLL3 targeted trispecific T cell engager with integrated CD28 co-stimulation, demonstrates safety and potent preclinical efficacy in models of small cell lung cancer (GlobeNewswire) - "ZW209 was designed for optimal T cell binding and enhanced target-dependent T cell activation that translates to increased antitumor activity compared to traditional bispecific T cell engagers; Relative to other DLL3 targeted T cell engagers in development, ZW209 exhibits enhanced and prolonged cytotoxicity over repeated tumor cell challenges and at low effector to target cell ratios. These data reinforce the potential of ZW209 to increase the depth and durability of responses in DLL3-expressing tumors by increasing T cell responses, which may translate to improved clinical outcomes; In a non-human primate (NHP) study, ZW209 demonstrated favorable pharmacokinetics (PK) and safety following repeat dosing."

Preclinical • Small Cell Lung 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 Hosts R&D Day Highlighting Continued Clinical Progress in Oncology Programs... (GlobeNewswire) - "The Company expects to submit an IND and non-U.S. applications to commence Phase 1 clinical studies for ZW209 in 1H-2026...The Company expects to submit an IND and non-U.S. applications to commence Phase 1 clinical studies for ZW251 in 2H-2025...The Company continues to develop and advance additional solid tumor product candidates beyond the 5 x 5 portfolio, with a specific focus on GI tract cancers, supporting further potential IND applications in 2027 and beyond."

IND • New P1 trial • Hepatocellular Cancer • Oncology

Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024 American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Abstract: 6716:...Key Results: Induces greater in vitro cytotoxicity and improves T cell proliferation and survival compared to bispecific TCEs. Displays no cross-linking of T cells and exhibits obligate cis T cell binding of CD28, requiring co-engagement of CD3. Mediates improved in vivo tumor regression in an established SCLC humanized xenograft model relative to a clinical benchmark TCE."

Preclinical • Small Cell Lung Cancer

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