On March 8, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported that it will present the first data from its preclinical synthetic lethality pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022, in New Orleans, LA (Press release, Calithera Biosciences, MAR 8, 2022, View Source [SID1234609679]).
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The accepted poster will detail Calithera’s discovery of a novel series of vacuolar protein sorting-associated protein 4A (VPS4A) inhibitors that are currently advancing through lead optimization. VPS4A and VPS4B are paralog ATPases essential for remodelling intracellular organelle membranes. Membrane remodelling is an essential cellular function and loss of function of both VPS4 paralogs is lethal to cells. The preclinical data demonstrate that VPS4A genetic inhibition in cell lines with loss of VPS4B preferentially showed profound death in cancer cells.
"The data being shared at the AACR (Free AACR Whitepaper) annual meeting suggest that inhibition of VPS4A is a promising approach to treat cancers across a wide variety of cancer types that harbor VPS4B deletions. We believe the discovery of this series of VPS4A inhibitors is a significant step forward in our efforts to expand our pipeline of targeted therapies to ultimately treat patients with high unmet need," said Susan Molineaux, chief executive officer of Calithera. "Additionally, we are excited about the progress we have made in advancing these discoveries as we focus on lead optimization. Synthetic lethal cancer therapies are highly promising, and we look forward to contributing to this rapidly advancing field with this novel mechanism."
Calithera is building a robust preclinical pipeline of additional synthetic lethality targets with a continuing focus on paralog genes. Gene paralog pairs represent a promising class of synthetic lethal cancer targets. When a tumor cell loses one paralog, the cell is dependent on the second paralog to carry out an essential cellular process, since loss of both paralogs leads to tumor cell death. Calithera researchers have confirmed VPS4A and VPS4B as synthetic lethal paralog pairs, noting that both homozygous and heterozygous loss of VPS4B in cancer cells makes them vulnerable to VPS4A inhibition. VPS4B is lost in a heterozygous fashion in the majority of colorectal cancer, pancreatic ductal adenocarcinoma, ovarian, esophageal and head & neck cancers and is deleted in large numbers of other tumor types. At AACR (Free AACR Whitepaper) 2022, Calithera will report the discovery of a series of novel, small-molecule VPS4A inhibitors which have potential in the treatment of VPS4B-deleted tumors.
Details of the abstract accepted for presentation at AACR (Free AACR Whitepaper) 2022 (#1816) are as follows:
Title: Identification of novel VPS4A inhibitors for the treatment of VPS4B-deleted cancers
Session Category: Experimental and Molecular Therapeutics/Drug Targets
Session Title: Drug Targets
Date and Time: Monday Apr 11, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 23
Poster Board Number: 14
Permanent Abstract Number: 1816
Presenter: Meredith Kuo, Ph.D.
This abstract is currently available on the AACR (Free AACR Whitepaper) website, and the poster will be available on Calithera’s website on April 8, 2022.