Zymeworks Presents New Preclinical Data at AACR 2026 Highlighting Broad Antibody-Drug Conjugate Programs Including Novel RAS-Targeting Platform
- Six poster presentations showcase Zymeworks’ next-generation ADC programs, including multiple first-in-class pan-RAS inhibitor ADCs
- Data highlight efficacy, tumor-selective delivery, and favorable tolerability across multiple solid tumor models
- New programs include Ly6E, CLDN18.2, and PTK7-targeting ADCs, as well as novel payload and platform innovations
- New clinical data from Phase 1 trial of ZW191 to be presented in an oral presentation on
April 21
“Our AACR presentations highlight the breadth and depth of our ADC platforms, including multiple novel approaches to targeting RAS-driven cancers,” said
Poster Presentation Highlights
ZW191 - a differentiated FRα-targeted topoisomerase I antibody drug conjugate active in combination with standard of care drugs
Abstract: 1707
Session: Experimental and Molecular Therapeutics
ZW191 is a clinical-stage (NCT06555744) folate receptor alpha (FRα)-targeting antibody-drug conjugate featuring a novel antibody and a moderate-potency, bystander-active topoisomerase I inhibitor payload (TOPO1i), ZD06519, designed to drive improved efficacy and tolerability versus existing FRα-targeted ADCs. In nonclinical studies, ZW191 demonstrates activity across all levels of FRα expression and shows promising combination potential with standard-of-care therapies, supported by a favorable tolerability profile.
Key non-clinical findings include:
- Differentiated by its superior internalizing novel antibody and moderate potency novel TOPO1i payload.
- Favorable tolerability profile, attributed to moderate potency TOPO1i payload and moderate stability linker, potentially achieves higher ADC dosing, better tolerability and improved combination potential with standard of care chemotherapeutics.
- Nonclinical in vitro and in vivo studies support the efficacious combination of ZW191 with standard of care therapies across multiple modes of action.
A pan-RASi antibody drug-conjugate platform with high activity in RAS sensitive cancers
Abstract: 1642
Session Category: Experimental and Molecular Therapeutics
Zymeworks’ RASi-ADC platform integrates novel tricomplex pan-RAS inhibitors into ADCs to enable tumor-selective delivery and improved therapeutic index.
Key findings include:
- Strong regressions observed in multiple tumor models at single doses as low as 1 mg/kg
- ADC delivery demonstrates improved tumor selectivity compared to orally administered RAS inhibitors
- Favorable tolerability observed in rodents and non-human primates
- Platform supports development of broadly applicable ADCs for RAS-mutated cancers
Development of ZW418, a biparatopic PTK7-targeting antibody-drug conjugate incorporating a novel pan-RAS inhibitor payload for the treatment of non-small cell lung cancer
Abstract: 4944
Session Category: Experimental and Molecular Therapeutics
ZW418 is a first-in-class biparatopic ADC targeting PTK7, designed to enhance binding, internalization, and delivery of a pan-RAS inhibitor payload in non-small cell lung cancer (NSCLC).
Key findings include:
- Strong anti-tumor activity observed across PTK7-expressing RAS-mutant NSCLC xenograft models, at doses as low as 1 mg/kg
- Biparatopic design enhances receptor engagement, internalization, and payload delivery
- Selective cytotoxicity in KRAS-mutant tumor cells while sparing normal tissues
- Favorable pharmacokinetics and tolerability support further development
ZW427, a Ly6E-targeting antibody-drug conjugate bearing a novel pan-RAS inhibitor payload for the treatment of RAS mutated cancers
Abstract: 7715
Session Category: Experimental and Molecular Therapeutics
ZW427 is a first-in-class ADC targeting Ly6E, designed to deliver a novel pan-RAS inhibitor payload to tumor cells in colorectal (CRC), pancreatic (PDAC), and lung cancers.
Key findings include:
- Robust anti-tumor activity observed across CRC, PDAC, and NSCLC xenograft models with a range of Ly6E expression
- Targeted delivery enables sustained RAS inhibition in tumors with reduced activity in normal tissues such as skin and colon
- Favorable tolerability observed in rodents and non-human primates at exposures exceeding projected efficacious doses
- Potential to improve efficacy and safety profile compared to small molecule pan-RAS inhibitors
ZW439, a novel CLDN18.2-targeting pan-RAS inhibitor antibody-drug conjugate for the treatment of RAS mutated pancreatic cancer
Abstract: 4556
Session Category: Experimental and Molecular Therapeutics
ZW439 is a novel ADC targeting CLDN18.2, designed to deliver a pan-RAS inhibitor payload in pancreatic ductal adenocarcinoma.
Key findings include:
- Strong anti-tumor activity observed in CLDN18.2-expressing RAS-mutant xenograft models, at doses as low as 1 mg/kg
- Target-dependent delivery of pan-RAS inhibitor payload with potent RAS pathway inhibition and cytotoxicity
- Robust bystander activity supports activity in heterogeneous tumors
- Favorable pharmacokinetics and tolerability compared to small molecule RAS inhibitors
Design and evaluation of mRNA translation inhibitors for use as antibody drug conjugate payloads
Abstract: 2062
Session Category: Experimental and Molecular Therapeutics
Key findings include:
- Over 40 novel eIF4A inhibitor payloads synthesized spanning a range of potency and hydrophilicity
- Hydrophilic linker designs improve both efficacy and tolerability in vivo
- Demonstrated robust anti-tumor activity across multiple targets including HER2, TROP2, EGFR, Ly6E, and PTK7
- Represents a novel payload class with potential to overcome resistance to existing ADC payloads
Posters are available on the Company’s website located at https://www.zymeworks.com/publications/.
Oral Presentation Details
Results from Part 1 dose escalation of ZWI-ZW191-101 study: Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)–targeting antibody-drug conjugate (ADC), in participants with advanced solid tumors
Abstract: CT306
Session: Advances in Precision Oncology
Lead author
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