Sanofi disclosed this morning that it has removed three candidates from its phase 1 pipeline. \n Sanofi is tight-lipped about the future of its underwhelming pact with Denali Therapeutics after the French pharma scrapped what appeared to be the final RIPK1 inhibitor from the deal.The Paris-based drugmaker revealed in its full-year 2025 earnings results (PDF) this morning that it has deprioritized eclitasertib, a receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor Sanofi had been assessing in a phase 2 study for ulcerative colitis (UC).Sanofi paid Denali $125 million upfront back in 2018 in the belief inhibiting the kinase may stop tissue damage and neuronal death by disrupting the production of cytokines and other proinflammatory factors. But, across seven years of effort, Sanofi has failed to validate the idea in the clinic.The two companies stopped development of their original lead candidate in 2020 in response to preclinical chronic toxicity studies. They instead turned their attention to oditrasertib, only to report phase 2 failures in both amyotrophic lateral sclerosis and then multiple sclerosis.That left eclitasertib, a peripherally restricted drug candidate that flunked a phase 2 test in cutaneous lupus erythematosus in 2023 but had remained in development for UC—until today.When asked by Fierce Biotech whether the deprioritization of eclitasertib’s UC program marks the end of the long-suffering Denali pact, Sanofi executives were noncommittal.“This is not the time to comment on the progress of that collaboration,” Sanofi\'s head of R&D Houman Ashrafian, Ph.D., told Fierce during a call with journalists this morning. “We are committed to all of our partners,” he added.Other companies have shared Sanofi’s interest in RIPK1 as well as its struggles to take their assets forward. GSK previously dropped one RIPK1 cancer candidate and offloaded another to Boston Pharmaceuticals in 2021, while Bristol Myers Squibb removed a phase 1 RIPK1 inhibitor from its pipeline in 2023. Just two months ago, Eli Lilly pulled out of the central nervous system-focused portion of a $960 million biobucks deal centered on Rigel Pharmaceuticals’ RIPK1 inhibitors.When asked by Fierce why so many companies have struggled to develop RIPK1 inhibitors, Ashrafian acknowledged the “complicated” nature of these programs carried out across the industry.“The only comment I\'d make about our partnered RIPK1 programs is the chemistry was excellent,” he said. “So it gives us an opportunity to continue to reflect on how as [a] mono and combination therapy, that particular node is optimally drugged.” Trio of phase 1 drugs dropped Further back in development, Sanofi also disclosed this morning that it has removed three candidates from its phase 1 pipeline. They included SAR445514, a BCMA-targeting NK cell engager licensed from Innate Pharma for inflammatory indications, as well as SAR446159, a brain-shuttled antibody that had been investigated for Parkinson’s disease.The other scrapped candidate was an mRNA flu vaccine called SP0237, which as recently as 2024 was hailed by Sanofi executives as the “next stage” of Sanofi\'s mRNA flu development.While Sanofi’s leadership didn’t reference SP0237 specifically on this morning’s call, CEO Paul Hudson did stress in general terms that whether it\'s vaccines or any other modality, “we don\'t make clinical decisions based on politics or sentiment in the now.”However, the CEO acknowledged the impact of the changing stance of the U.S government to vaccines.“You\'ve seen some of the complexity around the change in leadership in healthcare in the United States,” Hudson said. “We\'re not complaining, we just recognize that the vaccine coverage rates will have dipped a little because of the debates that are happening in the public.”But, despite this dip in coverage rates, Sanofi—which markets Fluzone and respiratory syncytial virus shot Beyfortus—gained market share last year, said Hudson.The CEO also pointed out that the company continued to add to its vaccine business, notably with the $2.2 billion acquisition of Dynavax Technologies last month.
