Eli Lilly hands over $125M to Rigel with $835M in biobucks for RIPK1 inhibitors

Eli Lilly has penned a research and sales pact with Rigel Pharmaceuticals for its experimental med R552, a receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor.

The pact, worth $125 million upfront and wedded to $835 million in biobucks, is focused on all indications for the phase 2-ready med, including in autoimmune and inflammatory diseases. As part of the deal, Lilly will also lead all clinical development of brain-penetrating RIPK1 inhibitors in central nervous system (CNS) diseases.

Lilly will be responsible for all costs of global sales for R552, while Rigel has the rights to co-sell R552 in the U.S. Lilly will be solely responsible for all development and commercialization of brain-penetrating RIPK1 inhibitors in CNS indications.

Recent research suggests RIPK1 activation plays a key role in programmed cell death, too much of which can lead to inflammation. Normally, cells maintain a proper balance by cleaving RIPK1 with an enzyme called caspase-8. In this autoinflammatory disease, the mutations are preventing the molecule from being cleaved into two pieces, resulting in uncontrolled cell death and inflammation.

It’s still early days in research for the target, but there have been hiccups: In 2019, GSK dropped its RIPK1 inhibitor GSK095 for pancreatic cancer, which was “terminated as part of ongoing portfolio prioritisation,” the Big Pharma said at the time.

But the target has been of interest to fellow European pharma Sanofi, which has a deal with Denali for a stake in two RIPK1 inhibitors at the biotech, designed to treat multiple neurodegenerative and systemic inflammatory diseases.

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Rigel has already proven a different platform after getting the FDA nod a few years back for Tavalisse (fostamatinib disodium hexahydrate), which works as an oral spleen tyrosine kinase inhibitor for patients with chronic immune thrombocytopenia as a second-line therapy.

“At Lilly, our immunology strategy is focused on the pursuit of novel targets that have the potential to develop into best-in-class medicines for patients with autoimmune conditions,” said Ajay Nirula, M.D., Ph.D., vice president of immunology at Lilly. “RIPK1 inhibitors are a promising approach, and R552 is an exciting addition to our immunology pipeline. We look forward to working with Rigel to advance its clinical development.”

Rigel shares jumped 23% premarket on the news.

“We are very excited to form this strategic partnership with Lilly. This collaboration will provide significant resources and expertise to support a broad investigation in multiple disease indications with our RIPK1 inhibitors,” added Raul Rodriguez, Rigel's president and CEO.

“With Lilly's extensive knowledge in immune and CNS diseases, they are our ideal partner to ensure the clinical and commercial success of our RIPK1 inhibitor program.”