Bristol Myers jumps into synthetic lethality with $65M Repare deal

As it ushers the CAR-T treatments it picked up from Celgene toward approval, Bristol Myers Squibb is already working on its next chapter. It’s teaming up with Repare Therapeutics to find new synthetic lethality targets in a deal that could be worth billions.

The duo will use Repare’s screening technology to pinpoint multiple targets for new cancer drugs. The Big Pharma is handing over $65 million upfront, including $15 million in equity, but is promising up to $3 billion in license fees, as well as assorted milestone payments.

Repare’s CRISPR-based platform identifies synthetic lethal gene pairs, which cause cell death when both genes are inactivated. In cancer cells, one of these genes is inactivated by a mutation; the other will be switched off by a drug.

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There are multiple drugs on the market that bring about this type of synthetic lethality, including AstraZeneca and Merck’s Lynparza and Zejula from Tesaro, now part of GlaxoSmithKline. Both block the enzyme PARP to treat BRCA-mutant ovarian cancer. BMS and Repare are on the hunt for more targets like PARP.

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“This collaboration will help to ensure that our novel discoveries are being broadly prosecuted in the search for the next generation of precision oncology medicines,” said Repare CEO Lloyd Segal, in a statement on Tuesday. “Bristol Myers Squibb brings key strategic capabilities to this partnership and the resources to maximize our platform’s potential while allowing us to independently focus on our proprietary clinical and near-clinical programs.”

Repare snagged $82 million last fall to move its most advanced program into the clinic in 2020, with another following close behind. Dubbed RP-3500, the lead program inhibits ATR, which protects cells from replication-related stresses. It hasn’t disclosed much about the second program, code-named “Manchester,” which targets a synthetic lethal pair involving the CCNE1 gene.