On March 13, 2018 IDEAYA Biosciences, Inc., an oncology-focused biotechnology company committed to the discovery of breakthrough synthetic lethality medicines and immuno-oncology therapies, reported that it has entered into a partnership agreement with Cancer Research UK’s (CRUK) Commercial Partnerships Team and the Drug Discovery Unit at the Cancer Research UK Manchester Institute, part of the University of Manchester, UK, to develop small molecule inhibitors of Poly(ADP-ribose) glycohydrolase (PARG) (Press release, Ideaya Biosciences, MAR 13, 2018, View Source [SID1234525131]). PARG is a cellular enzyme that breaks down Poly(ADP-ribose), a post-translational modification that modulates protein function required for DNA repair. Inhibition of PARG in cancer cells with highly-active PARP results in depletion of cellular NAD. NAD is an essential cofactor in cellular respiration, and its depletion results in a dramatic decrease in cellular ATP and cancer cell death.

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"We are thrilled to be able to partner with one of the leading cancer research institutions in CRUK, who has had a prolific history in the space of DNA repair, including its scientific contributions to PARP biology and its associated biomarker BRCA," said Yujiro S. Hata, chief executive officer of IDEAYA. "We look forward to collaborating with this exceptional organization as we advance novel, small molecule inhibitors of PARG towards the clinic."

"The Drug Discovery Unit at the Cancer Research UK Manchester Institute are delighted to be working alongside IDEAYA to further develop our PARG inhibitor program," said Allan Jordan, head of chemistry in the Drug Discovery Unit. "Stemming from fundamental biological discoveries made in our own Institute, PARG inhibitors offer a new way of compromising the ability of cancer cells to survive and resist treatment. We believe that these agents will offer a truly novel and clinically meaningful therapy for patients fighting against cancer.

"This new collaboration with IDEAYA, a leading biotechnology company, will accelerate the translation of discoveries from one of our major drug discovery units," said Iain Foulkes, Ph.D., Cancer Research UK’s executive director of research and innovation. "We’re excited to focus our combined expertise on this unique program of research. This is one of several partnerships in our growing portfolio of projects that we hope will result in vital new treatments for cancer patients."

IDEAYA and Cancer Research UK also announced today that data from the PARG program will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held April 14-18, 2018 in Chicago, IL. The presentation details are as follows:

Title: PARG inhibitors exhibit synthetic lethality with XRCC1 deficiency and a cellular mechanism of action that is distinct from PARP inhibition
Date and Time: Monday, April 16, 8:00 AM – 12:00 PM CDT
Abstract Number: 1943
Presenting author: Lisa Belmont, Ph.D.
Session Category: Experimental and Molecular Therapeutics