In a deal potentially worth $3 billion, privately held Repare Therapeutics Inc., of Cambridge, Mass., and Montreal, entered a research collaboration with Bristol Myers Squibb Inc. (BMS) to identify synthetic lethal precision oncology targets for drug candidates.

Repare is eligible to receive about $3 billion in license fees, discovery, development, regulatory and sales-based milestones. The company is also set to receive from BMS an up-front payment of $65 million, including a $15 million equity investment. Royalty payments on net sales of all products that BMS commercializes in the deal could also go to Repare.

In exchange, BMS received exclusive worldwide rights for developing and commercializing selected oncology targets discovered in in the collaboration.

Both companies will use Repare’s CRISPR/Cas9-based chemogenomic screening platform, SNIPRx, to identify the targets. The platform uses isogenic cells lines to identify genomic alterations, including DNA damage repair,  and then match the patients with a therapy based on the tumor’s genetic profile.

Repare is doing preclinical research into its lead candidate is RP-3500, an ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor, a master DNA damage response regulator that works in concert with a second kinase, ataxia-telangiectasia mutated (ATM), to maintain genomic stability in response to DNA damage. Cancers with ATM mutations may therefore be targeted with ATR inhibitors. The platform is designed to find dependencies between ATR and unidentified genes.

Repare and BMS now join others targeting ATR, including Leverkusen, Germany-based Bayer AG, Cambridge, U.K.-based Astrazeneca plc and Darmstadt, Germany-based Merck KGaA.

Repare’s CEO, Lloyd Segal, said his company’s platform has an edge over the competition because it can select patients based on criteria beyond just ATM deletions.

Repare has a second program, Manchester, which targets an undisclosed targeted mutation that is synthetically lethal when paired with mutations in CCNE1-SL, which encodes the cell cycle protein cyclin E1. Manchester is in the lead optimization phase, poised to soon go into preclinical research.

The company also has a Polθ inhibitor program that is in the lead generation phase targeting the cancer risk gene BRCA.

In June 2017, a series A worth $68 million helped Repare launch its R&D into ATR. Last September, Repare raised $82.5 million in a series B with help from a syndicate led by Cowen Healthcare Investments. Other participants included Orbimed, Redmile, BVF Partners LP and Logos Capital, as well as founding investors Versant Ventures and other existing investors MPM Capital, Fonds de Solidarité FTQ and BDC Capita.

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