ZYME - Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024 American Association for Cancer Research Annual Meeting | Benzinga
VANCOUVER, British Columbia, April 08, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (NASDAQ:ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today announced five presentations including new data from its preclinical development-stage programs at the 2024 American Association for Cancer Research (AACR) Annual Meeting being held in San Diego, California April 5-10, 2024.
"Our team is looking forward to share new data from our strong portfolio of multispecific antibody therapeutics and antibody-drug conjugates including ZW191, an anticipated 2024 IND candidate," said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. "These data provide important new insights highlighting the potential of our candidates to represent major advances in the treatment of cancer while also demonstrating the potential to develop a new generation of novel antibody-drug conjugates and multispecific antibody therapeutics."
Presentation Highlights
ZW191 - a FR?-targeting antibody-drug conjugate with strong preclinical activity across multiple FR?-expressing indications
Abstract: 1862
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody-Based Technologies and New Inhibitors
ZW191 is a FR?-targeting antibody-drug conjugate (ADC) differentiated by its novel antibody and novel topoisomerase I inhibitor payload. The compelling preclinical activity profile supports ZW191 development across multiple tumor types, including FR?-high/mid/low ovarian cancers and other FR?-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 FR?-targeted multi-specific antibodies.
- Bystander active payload drives activity in settings with heterogeneous FR? expression.
- Well-tolerated, with a highest non-severely toxic dose of 60 mg/kg in non-human primates.
Screening novel format antibodies to design bispecific ADCs that address target heterogeneity
Abstract: 2052
Session Category: Experimental and Molecular Therapeutics
Session Title: New Technologies
Inter-patient and intra-tumoral target expression heterogeneity is an obstacle in the design of ADCs that target a single tumor associated antigen (TAA). While bystander active payloads mitigate intra-tumoral target heterogeneity, bispecific ADCs that target two different TAAs independently provide an additional approach to overcome limitations associated with the expression profile of any single target antigen. Critical to this bispecific ADC approach however is identification of the optimal bispecific antibody format suited for payload delivery to two independent tumor antigens. To address this challenge a novel design and screening approach of bispecific ADCs was employed, using FR? and NaPi2b as an exemplary target pair, independently expressed across various cancer types.
Key Results:
- Leveraging Azymetric™, bioconjugation, analytical mass spectrometry, and high throughput functional screening, a workflow for the rapid generation and characterization of bispecific ADCs was established to identify optimal format, paratope, and valency.
- A library of 48 bispecific ADC molecules co-targeting FR? and NaPi2b was rapidly generated covering multiple paratopes, antibody formats, and valency bins (1+1, 2+1, 2+2). Functional screening of the library across multiple cancer cell lines expressing FR? and/or NaPi2b revealed ranges in binding, internalization, and cytotoxicity that were dependent on epitope, valency, and format geometry.
Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugates
Abstract: 3127
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody-Drug Conjugates
Antibody-drug conjugates are an effective class of cancer therapeutics comprised of a linker-payload conjugated to a monoclonal antibody targeting a TAA, to enable the delivery of the cytotoxic payload to cancer cells. Current standard in vitro monolayer models do not sufficiently reflect in vivo tumor tissue complexity, particularly in consideration of the interaction between protein-based therapeutics such as antibodies in a three-dimensional (3D) environment. To address this, methodology to yield in vitro 3D spheroid models from cancer cell lines in a rapid, robust, and uniform manner was developed. Subsequently methods were integrated to evaluate the tissue penetration capability and cytotoxic activity of structurally distinct antibodies or ADCs bearing various payload classes targeting multiple ...