Zymeworks to Present Clinical and Preclinical Data on ADC Programs Including Novel RAS ADC Platform at AACR Annual Meeting
- New clinical data from Phase 1 trial of ZW191 to be presented in an oral presentation on
April 21 - Preclinical data highlight combination potential for ZW191, a folate receptor alpha (FR⍺)-targeting antibody-drug conjugate (ADC)
- New ADC candidates, including ZW427, ZW439, and ZW418, demonstrate strong activity across RAS-mutated cancers based on a novel pan-RAS inhibitor ADC platform
“We are excited to share new clinical and preclinical updates at AACR that highlight the breadth of our ADC portfolio and the continued evolution of our platform technologies,” said
Oral Presentation Details
Title: 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
Date/Time:
“We look forward to presenting additional clinical data from Part 1 of our Phase 1 trial of ZW191, our FR alpha targeting ADC with our proprietary topoisomerase 1 inhibitor payload, in patients with advanced solid tumors,” said
Poster Presentation Details
Title: 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
Date/Time:
ZW191 is a clinical-stage ADC targeting folate receptor alpha (FRα), currently under investigation in patients with advanced ovarian, endometrial, and non-small cell lung cancers (NSCLC). New preclinical data demonstrate strong anti-tumor activity when ZW191 is combined with standard-of-care agents, including carboplatin, paclitaxel, bevacizumab, and PARP inhibitors, driven by enhanced DNA damage in tumor cells. Together with encouraging early clinical data highlighting ZW191’s single-agent activity and differentiated safety profile, the findings support its potential to deliver meaningful efficacy improvements across multiple cancer types and treatment settings.
Title: A pan-RASi antibody-drug conjugate platform with high activity in RAS-mutant cancers
Abstract: 1642
Session: Experimental and Molecular Therapeutics
Date/Time:
A novel ADC platform has been developed to overcome the efficacy and tolerability limitations of current oral pan-RAS inhibitors, which despite clinical promise are associated with on-target toxicities in normal tissues. The platform incorporates newly synthesized pan-RAS inhibitor payloads demonstrating higher potency than the clinical benchmark RMC-6236, with optimized drug-linkers showing strong tumor regressions at low doses and no significant toxicity at high doses in preclinical models. These findings establish a highly promising pan-RASi ADC platform with the potential to deliver improved efficacy and tolerability across multiple RAS-driven cancers, including NSCLC, pancreatic, and colorectal cancer.
Title: 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: 1686
Session: Experimental and Molecular Therapeutics
Date/Time:
ZW418 is a novel biparatopic ADC targeting PTK7, a protein broadly overexpressed in NSCLC, and delivering a novel pan-RAS inhibitor payload designed to improve upon the efficacy and tolerability limitations of current RAS inhibitors. Preclinical data demonstrate superior internalization and tumor penetration compared to clinical benchmark PTK7-targeted antibodies, alongside potent and targeted tumor cell killing and strong anti-tumor activity across multiple RAS-mutated cancer models. These findings support ZW418’s potential as a highly differentiated therapeutic for NSCLC patients whose tumors are driven by RAS mutations.
Title: ZW427, a Ly6E-targeting antibody drug conjugate bearing a novel pan-RAS inhibitor payload for the treatment of RAS mutated cancers
Abstract: 4431
Session: Experimental and Molecular Therapeutics
Date/Time:
ZW427 is a novel ADC targeting Ly6E, a protein broadly overexpressed across multiple solid tumors, and delivering a novel pan-RAS inhibitor payload designed to improve upon the efficacy and tolerability limitations of current small molecule RAS inhibitors. Preclinical data demonstrate ZW427’s potent and targeted tumor cell killing, strong bystander activity, and anti-tumor activity across multiple RAS-mutated cancer models including NSCLC, pancreatic, and colorectal cancers. These findings support ZW427’s potential as a highly differentiated therapeutic for the large population of cancer patients whose tumors are driven by aberrant RAS signaling.
Title: ZW439, a novel CLDN18.2-targeting pan-RAS inhibitor antibody drug conjugate for the treatment of RAS mutated pancreatic cancer
Abstract: 5640
Session: Experimental and Molecular Therapeutics
Date/Time:
ZW439 is a novel ADC targeting Claudin 18.2 (CLDN18.2) and delivering a novel pan-RAS inhibitor payload, designed to address the urgent unmet need in pancreatic cancer. Preclinical data demonstrate ZW439’s potent and targeted tumor cell killing across a range of CLDN18.2 expression levels, strong bystander activity, and highly efficacious anti-tumor activity in multiple cancer models, alongside an encouraging tolerability profile. These findings support ZW439’s potential as a differentiated therapeutic for patients with pancreatic cancer and other difficult-to-treat tumors driven by RAS mutations.
Title: Design and evaluation of mRNA translation inhibitors for use as antibody drug conjugate payloads
Abstract: 2400
Session: Chemistry
Date/Time:
A novel ADC platform has been developed incorporating newly synthesized eIF4A inhibitor payloads, which block translation of key oncogenic proteins including MYC and KRAS, offering a differentiated mechanism with the potential to address resistance seen with other ADC payload classes. Preclinical data demonstrate potent and targeted tumor cell killing in vitro and promising anti-tumor activity across multiple clinically relevant targets in vivo, including HER2, Ly6E, TROP2, and EGFR.
The AACR abstracts are available at https://www.abstractsonline.com/pp8/#!/21436.
Invited Talks
Senior members of Zymeworks’ research team will be speaking at the following sessions:
Title: Unlocking novel biologies with bi- and trispecific antibodies: the importance of antibody format
Speaker: Dr.
Date/Time:
Title: The (r)evolution of antibody-drug conjugates: From early concepts to next-generation cancer therapy
Speaker: Dr.
Date/Time:
About ZW191
ZW191 is an antibody-drug conjugate engineered to target a protein called folate receptor-⍺ found in ~75% of high-grade serous ovarian carcinomas1 and ~70% of lung adenocarcinomas2. ZW191’s differentiated design strongly supports its ability to internalize into FR⍺-expressing cells with the potential to release bystander active topoisomerase-1 inhibitor (ZD06519), a novel proprietary payload developed by Zymeworks to kill tumor cells.
ZW191 is currently being evaluated in a Phase 1 clinical study to assess its safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity in participants with advanced solid tumors (NCT06555744). The study is designed to further characterize ZW191’s clinical activity and safety to inform its future development strategy.
About
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Investor Inquiries:
Vice President, Investor Relations
(604) 678-1388
ir@zymeworks.com
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Vice President, Corporate Communications
(604) 678-1388
media@zymeworks.com
1 Köbel, M., Madore, J., Ramus, S. et al., Br J Cancer 111, 2297–2307 (2014).
2 O'Shannessy DJ, et al., Oncotarget. 2012 Apr; 3(4):414-25.
Source: Zymeworks Inc.