Cyteir Therapeutics Presents Preclinical Data Validating RAD51-AID As A Novel Target For Cancer Treatment At AACR Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Cyteir Therapeutics a leader in the development of novel therapeutics based on the biology of DNA repair and synthetic lethality, today announced that it will present preclinical data validating RAD51-AID as a synthetic lethal pair and novel target for cancer treatment at the American Association of Cancer Research (AACR) Annual Meeting in Washington, D.C.

“Our small molecule RAD51 modulators continue to demonstrate potent, selective effects on disease-causing cells in vitro and in vivo while remaining well tolerated in preclinical animal models of leukemia and lymphoma. We look forward to exploring the full potential of this therapeutic approach in multiple tumor types.”

The preclinical studies build upon the previous observation that RAD51-AID synthetic lethality occurs via mitotic catastrophe, a non-apoptotic cell death mechanism. In xenograft models of lymphoma and leukemia, potent and selective RAD51 modulatory small molecules were used to activate AID-induced cytotoxicity and preferentially induce cell death in AID-expressing tumor cells.

“These in vivo preclinical studies demonstrate that RAD51 modulation selectively induces cell death in AID-expressing cancer cells,” said Kevin D. Mills, Ph.D., Chief Scientific Officer of Cyteir. “Our small molecule RAD51 modulators continue to demonstrate potent, selective effects on disease-causing cells in vitro and in vivo while remaining well tolerated in preclinical animal models of leukemia and lymphoma. We look forward to exploring the full potential of this therapeutic approach in multiple tumor types.”

“The recent success of PARP inhibition as a DNA repair target has focused the field on the next set of synthetic lethal pairs, and our studies elucidate RAD51-AID as a novel target,” said Donald F. Corcoran, President and Chief Executive Officer of Cyteir. “This new preclinical data supports the continued development of selective small molecules that take advantage of this novel synthetic lethal pair. We will continue to optimize and study our lead compounds in order to identify a clinical candidate for cancer this year, and we further intend to evaluate whether our approach could be synergistic with PARP inhibition.”

Cyteir’s approach leverages the identification of activation induced cytidine deaminase (AID) as both a biomarker and driver of DNA damage. In cancer cells, induction of AID leads to increased genomic instability which causes an obligate dependency on the recruitment of the DNA repair protein, RAD51, for continued survival and growth of the cancer cell. By modulating RAD51 transport in AID-positive cancer cells, Cyteir seeks to induce their self-destruction by selectively blocking the repair of overwhelming DNA damage. Preclinical studies to date have demonstrated Cyteir’s RAD51 modulators to be potent, selective for AID-positive cells, effective against cancer cells in vitro and in vivo, and well tolerated in preclinical animal models.

Details of the presentation are as follows:

Title: RAD51 and AICDA define a new synthetic lethal interaction that is targetable in multiple tumor types
Poster: 2481
Session: Homologous Recombination and DNA Double-Strand Break Repair
Date: Monday, April 3, 2017
Time: 1:00pm – 5:00pm EDT
Location: Section 19, Exhibit Hall, Lower Level, Washington Convention Center

About Cyteir
Cyteir Therapeutics is a leader in the discovery and development of novel therapeutics based on the biology of DNA repair and synthetic lethality for the treatment of cancer and autoimmune diseases. Our initial approach takes advantage of DNA damage overload to induce selective self-destruction of cells by targeting disease-induced RAD51 transport. www.cyteir.com