Eli Lilly has pulled out of the central nervous system (CNS)-focused portion of a $960 million biobucks deal centered on Rigel Pharmaceuticals’ receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitors.
The deal, penned back in 2021, involved Lilly taking the lead in all clinical development and potential commercialization of brain-penetrating RIPK1 inhibitors for CNS diseases. At the time, Rigel had been conducting preclinical activities in relation to its lead CNS-penetrant RIPK1 inhibitor candidates.
However, Rigel disclosed in its third-quarter earnings release yesterday that the biopharma received notification from Lilly in early October that the pharma is now terminating this CNS collaboration.
Fierce Biotech has asked Lilly for the reasons for this decision but had not received a reply at time of publication.
The termination of the CNS collaboration is far from the end of Rigel’s partnership with Lilly. The real prize of the pact—which involved $125 million upfront and potentially $835 million in milestone payments totaling $960 million—was always the phase 2 -ready RIPK1 inhibitor ocadusertib.
Lilly has since taken ocadusertib into a phase 2 trial in adults with moderately to severely active rheumatoid arthritis, meaning those milestone payments remain in reach for Rigel.
Research has suggested 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.
RIPK1 inhibitors continue to receive interest from drug developers. In July, Novartis secured an option on the blood-brain-barrier-crossing platform from Sironax, the most advanced assets of which are a pair of RIPK1 inhibitors aimed at neurodegenerative diseases and immune/inflammatory diseases, respectively.
Meanwhile, Sanofi dropped a RIPK1 inhibitor from its pact with Denali Therapeutics after the drug flunked a phase 2 study in multiple sclerosis last year.