AbCellera Presents Data On T-Cell Engagers Against Four Tumor Targets At AACR 2024

Author: Benzinga Newsdesk | April 08, 2024 12:06pm

Data show how AbCellera is expanding the reach of T-cell engagers with:

• CD3-binding antibodies that consistently generate T-cell engagers with potent tumor-cell killing and low cytokine release across multiple tumor targets, including PSMA, B7-H4, and 5T4
• Costimulatory CD28-binding antibodies that stimulate T cells without superagonist activity
• Highly specific T-cell engagers for the peptide-MHC target MAGE-A4

AbCellera (NASDAQ:ABCL) today announced new data on its T-cell engager (TCE) programs at the American Association for Cancer ResearchⓇ (AACR) Annual Meeting 2024 at the San Diego Convention Center, with three posters being presented on April 8 and one on April 9. Together, AbCellera's data demonstrate that it is well-positioned to advance TCEs as a drug class by widening the therapeutic window, enhancing potency, and broadening the accessible target space.

"TCEs are among the most promising new modalities in cancer therapy, but limitations in efficacy and safety have been barriers to realizing their potential for solid tumor indications," said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "Our data illustrate that we can repeatedly generate TCEs that maximize tumor-cell killing without inducing excessive cytokine release. Reducing the risk associated with CD3 engagement could improve efficacy both by widening the therapeutic window and by creating opportunities to further enhance potency through co-stimulatory modalities."

AbCellera's poster presentations, which are available for viewing here, describe how AbCellera is:

Widening the therapeutic window: AbCellera's data describe the generation of TCEs for three solid tumor targets, PSMA, B7-H4, and 5T4, with functional profiles that are differentiated from clinical benchmarks. These molecules were engineered using a specific set of rare CD3-binding antibodies that consistently show potent tumor-cell killing and low cytokine release across multiple targets, demonstrating their potential to expand the therapeutic window across solid tumor indications.

Enhancing potency: TCEs that engage the CD28 costimulatory receptor can enhance T-cell activation, proliferation, and anti-tumor activities, particularly in solid tumors. The data show that AbCellera's IgG and heavy chain-only CD28-binding antibodies do not display superagonist activity — a property associated with toxicity. Integrating costimulatory building blocks into AbCellera's TCE repertoire may enable development of molecules with enhanced potency for difficult-to-treat cancers.

Broadening the accessible target space: The target repertoire for TCEs has been restricted to proteins expressed on the surface of cancer cells. Intracellular peptides displayed on MHC class I (pMHCs) would greatly expand the target pool for TCEs. However, development of TCEs against pMHCs has been limited due to the high degree of target specificity required. Data illustrate how AbCellera is unlocking this target class by generating molecules with high specificity for MAGE-A4-pMHC, which showed little to no binding to hundreds of off-target pMHCs.

"Our platform for creating precision TCEs to address indications in cancer and autoimmunity provides a strong foundation for both internal programs and strategic partnerships," said Murray McCutcheon, Ph.D., SVP, Partnering at AbCellera. "We look forward to advancing these programs with the aim of delivering powerful new medicines for patients."

Posted In: ABCL