GS-3583

The pipeline changes leave the IRAK4 inhibitor GS-5718 only continuing on in lupus. With so many Big Pharmas reporting their full-year earnings yesterday, it was no surprise that drugmakers used the occasion as an excuse to slip out some pipeline changes. Gilead was no exception, removing a solid tumor candidate from its early-stage lineup along with two of the three indications for its IRAK4 inhibitor. One asset on the chopping block is a Fms-like tyrosine kinase 3 agonist dubbed GS-3583 that was being assessed in a phase 1b trial for patients with advanced solid tumors. Gilead terminated the 13-patient trial study early following an internal safety assessment of the molecule, according to ClinicalTrials.gov. The other two programs being cut are both for the same phase 1 inflammatory disease candidate: an interleukin-1 receptor-associated kinase 4, or IRAK4, inhibitor called GS-5718. Gilead is ending early-stage work evaluating the therapy in both inflammatory bowel disease and rheumatoid arthritis. It leaves GS-5718 only continuing on in lupus, according to Gilead’s earnings presentation. The IRAK-4 field received some positive coverage in December when Kymera Therapeutics linked its own candidate to improvements in symptoms of hidradenitis suppurativa and atopic dermatitis, encouraging its partner Sanofi to take the program forward. Unlike Gilead’s GS-5718, Kymera’s therapy degrades, rather than inhibits, IRAK-4. Gilead wasn’t alone in disclosing pipeline changes yesterday. The company, which hosted its earnings call after market close, joined four other Big Pharmas—Roche, Eli Lilly, Merck & Co. and Bristol Myers Squibb—that also shared program cuts earlier in the day as part of their own earnings announcements. Still, the California-based pharma touts 59 clinical programs and has more than doubled its pipeline programs over the last four years, CEO Daniel O’Day and Chief Medical Officer Merdad Parsey, MD., Ph.D., said on a post-market call with investors. The company—which anticipates an FDA decision for an expanded indication of its potential breast cancer blockbuster Trodelvy later this month—saw an increase in quarterly R&D spend driven by clinical studies in oncology and virology. The pharma has also buckled down on investing in its cell therapy pipeline, as highlighted  in a recent $225 million deal with Arcellx. “We're going into 2023 in a very strong position with our current medicines performing well and tremendous growth potential in our newer therapies, as well as those in development,” O’Day concluded. “What you can expect to see next is quarter-on-quarter execution, and even faster progress and greater impact in the future.”