Eli Lilly bolsters neuro, immunology pipeline via multi-drug alliance with Rigel


Eli Lilly is paying Rigel Pharmaceuticals $125 million up front to grab a share in the development of drugs that would give the company a new way to address inflammation in multiple diseases.

The Rigel drugs are small molecules that block RIPK1, a signaling protein that plays a role in inflammatory processes in cells. Indianapolis-based Lilly sees the drug as having potential applications treating autoimmune disorders and neurological diseases.

The most advanced RIPK1 inhibitor from Rigel is R552. In preclinical tests in mice, the South San Francisco-based biotech reported that the drug prevented joint and skin inflammation. Rigel has since evaluated the compound in a Phase 1 study that demonstrated safety in healthy volunteers. Mid-stage studies are slated to begin later this year under the collaboration with Lilly. According to deal terms announced Thursday, if R552 reaches the market, Lilly will be responsible for commercialization costs globally except for the U.S., where Rigel holds co-commercialization rights.

The other Rigel RIPK1-targeting drugs covered by the partnership are designed to penetrate into the central nervous system. These compounds are still preclinical, and the agreement makes Lilly responsible for all clinical development in CNS indications. If they’re approved, Lilly will also shoulder their commercialization. Under the deal, Rigel could earn up to $835 million in milestone payments, plus royalties from sales if the drugs covered under the partnership reach the market.

Lilly isn’t the only big pharma company in pursuit of drugs that block RIPK1. In 2018, Sanofi teamed up with Denali Therapeutics, paying the South San Francisco-based biotech $125 million up front to share in the development of two  drugs that block RIPK1. The brain-penetrating drug being developed for neurological indications—multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease—is in early clinical development. The other drug, which does not penetrate the brain, is also in early clinical development as a potential treatment for inflammatory disorders.

GlaxoSmithKline had its own RIPK1 inhibitor that it initially positioned as a potential pancreatic cancer drug. But in 2019 it stopped development of the early-stage compound with little explanation other than a brief mention in a pipeline update, FierceBiotech reported at the time.

Photo by Flickr user Paul Sableman via a Creative Commons license

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