Nurix Therapeutics Inc. landed its second big pharma collaboration in seven months when it signed with Sanofi SA to discover, develop and commercialize a pipeline of protein degradation therapies.

In the Sanofi deal, Nurix receives $55 million up front and is eligible for up to about $2.5 billion in total payments based on achieved milestones. To start, Nurix will design small molecules to induce degradation in three specific targets while Sanofi has the option to up the ante to five targets. Sanofi receives exclusive rights and will handle clinical development and commercialization and Nurix retains the option to co-develop and co-co-promote up to two products in the U.S.

For Arthur Sands, Nurix’s CEO, the proof in a deal’s pudding is the up-front payment, which he termed for this collaboration as “significant” and “substantial.”

“It’s always important to look at the up-front,” he told BioWorld. “That defines the magnitude of the commitment overall.”

Last June, Nurix inked a deal worth a potential $2.75 billion with Gilead Sciences Inc., and five years ago it entered a collaboration with Celgene Corp. by receiving a significant up-front fee.

Arthur Sands, CEO, Nurix

The Sanofi agreement means Nurix will hire some additional staff (it currently has 95 full-time employees) but the company’s infrastructure is in place as the technology is prepped to initiate and follow through on the deal, including the company’s DNA-encoded library.

“That’s the key first step, to initiate screening of these novel targets,” Sands said.

For programs that Nurix exercises its option to co-develop and co-promote, the two companies will split U.S. profits and losses 50-50. Nurix is eligible to receive royalties on ex-U.S. net sales on all optioned products.

“Those options are important for Nurix to further develop its own product portfolio,” Sands added. “Those are very valuable rights.”

The Sanofi deal excludes Nurix’s lead degradation programs, so Nurix also retains all the rights to those.

Nurix's platform can produce small-molecule candidates that are activators or inhibitors of both E3 ubiquitin ligases – the last in a series of three enzymes controlling placement of ubiquitin onto a protein, making it a key regulator in determining proteins' fates – and E2 ubiquitin-conjugating enzymes, a capability allowing them to disrupt or enhance protein-protein interactions.

Looking back at how the deal came together, Sands said the company is always in the mix by talking to potential partners. This deal, he said, took about a year to gel, starting with strategic conversations “with those who are cognizant of how the field is moving and where a company wants to go in terms of partnerships. The detail work and diligence usually take six months of real documentation.”

Gilead completed its massive deal with Nurix in June for E3 ligase modulating targeted protein degradation drugs for treating cancer and other diseases. In the multiyear collaboration, Nurix will identify agents using E3 ligases to induce degradation of specified drug targets, and Gilead will have an option to license drug candidates directed to up to five targets resulting from the work. Nurix retained the option to co-develop and co-detail up to two programs in the U.S.

In the Gilead deal, Nurix received $45 million up front and is eligible for about $2.3 billion in total additional payments based on the successful completion of certain research, preclinical, clinical, regulatory and commercialization milestones as well as up to low double-digit tiered royalties on net sales. For programs Nurix opts to co-develop and co-detail, the parties split development costs as well as profits and losses 50-50 for the U.S., with Nurix eligible for royalties on ex-U.S. sales and reduced milestone payments.

Back in 2015, Celgene tapped Nurix to discover and develop several new therapies targeting the ubiquitin proteasome system for the treatment of cancer, inflammation and immune disorders. The deal includes a $150 million up-front payment for Nurix, plus an undisclosed equity investment, validating earlier seed and series B investments by Third Rock Ventures and the Column Group that established the company.

Nurix is centralized in Mission Bay, a neighborhood on San Francisco’s east side.

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