Oditrasertib

Termination of a central nervous system collaboration is far from the end of Rigel Pharmaceuticals’ partnership with Eli Lilly. \n 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.

Plus, news about Rigel Pharmaceuticals, Ultragenyx, Neurocrine Biosciences, TransThera, MoonLake Immunotherapeutics, Kelonia Therapeutics, Johnson & Johnson and Harmony Biosciences: 🖊️ Eli Lilly signs deal with XtalPi subsidiary: Lilly will get access to Ailux’s AI-powered bispecific antibody engineering platform, with rights to nominate an undisclosed number of targets. The deal could be worth up to $345 million across upfront and milestone payments. Ailux is a wholly-owned subsidiary of Chinese biotech XtalPi. — Ayisha Sharma 🔬 Amgen stops trial of stomach cancer drug : Head of R&D Jay Bradner said that the company stopped a trial studying bemarituzumab in combination with chemotherapy and Opdivo for patients with first-line gastric cancer due to “inadequate efficacy.” The decision follows an updated analysis of the drug in a separate but similar trial showing that its overall survival benefit when combined with chemotherapy waned over time. A third study, FORTITUDE-103, is testing bemarituzumab in combination with other anti-cancer therapies and has completed enrollment, Amgen said. — Max Bayer 🛑 Lilly terminates CNS work with Rigel: Lilly notified the biotech early last month that it would end their partnership on a preclinical CNS disease program. That partnership was part of a deal announced in 2021 . But the companies will still partner on ocadusertib, which is an RIPK1 inhibitor in a Phase 2a study in certain rheumatoid arthritis patients with moderate to severe disease. – Reynald Castaneda 💼 Ultragenyx divests rare disease drug royalties to Canadian pension fund: The biotech will receive $400 million from OMERS. This is in return for a further 25% of Ultragenyx’s royalty interest from Kyowa Kirin on US and Canadian sales of Crysvita. Proceeds from the deal should help fund four of Ultragenyx’s upcoming launches. — Ayisha Sharma 🖊️ Neurocrine signs deal with TransThera: In an agreement worth up to $881.5 million, Neurocrine will have the rights to develop and commercialize the Chinese company’s preclinical NLRP3 inhibitors for a variety of diseases outside Greater China. – Reynald Castaneda 🌕 Moonlake sells $75M in shares: The drugmaker will use the proceeds to support continued development of its nanobody candidate, sonelokimab, for inflammatory diseases, among other purposes. The offering is expected to close on Nov. 6. The company also reported Wednesday that its 16-week data from a Phase 2 trial showed that palmoplantar pustular psoriasis patients treated with sonelokimab had an average 64% reduction in the area and severity of their psoriasis. — Ayisha Sharma 🤝 Kelonia Therapeutics’ new collaborator: Kelonia will be working with Johnson & Johnson to develop in vivo CAR-T therapies. The biotech will contribute the technology to engineer immune cells directly in the body and J&J will pick the targets. Financial and scientific details were not disclosed, but the deal makes J&J the latest entrant in the red-hot field. Four other pharma companies — AbbVie, AstraZeneca, Bristol Myers Squibb and Gilead Sciences — have acquired startups working on in vivo cell therapies this year. — Ryan Cross ⏸️ Harmony Biosciences said it is pausing work on ZYN002 for a genetic disorder called 22q11.2 deletion syndrome. The synthetic cannabidiol gel previously failed in a Phase 3 fragile X syndrome study. – Reynald Castaneda