GSK Halts Clinical Development of RIP1 Inhibitors GSK095 and GSK2982772 Amid Portfolio Prioritization

Compiled by Fan Dongdong

Last November, GSK published an article in *Cancer Cell* stating that preclinical studies had identified another RIP1 inhibitor, GSK547, which doubled survival time in animal models of pancreatic cancer. The study also demonstrated synergistic therapeutic effects when the drug was combined with immunotherapies such as PD-1 and ICOS inhibitors. These encouraging preclinical data prompted the company to confidently initiate a Phase I clinical trial of its investigational RIP1 inhibitor, GSK095. However, GSK’s recently released third-quarter financial report indicated that the development of GSK095 for pancreatic cancer would be discontinued as part of ongoing portfolio prioritization.

In the Phase 1 clinical trial of GSK095, GSK plans to enroll 220 patients with pancreatic cancer over two years to evaluate monotherapy and combination therapy with Keytruda.

GSK stated: “Following an internal review of its current R&D portfolio, the company has decided to terminate the pancreatic cancer study of GSK095.”

In a conference call with analysts and journalists this Wednesday, Dr. Hal Barron, Chief Scientific Officer and President of GSK, provided further details: “The drug has not been completely declared dead; it has merely returned to the research stage, and we are also considering other potential uses for it.”

In its product pipeline update, GSK added that another RIP1 inhibitor, GSK2982772, has also terminated its Phase 2 clinical studies. Specific details and reasons were not disclosed publicly, with the company simply stating that the drug would be “moved back to the research stage.” The drug had previously been studied in chronic inflammatory diseases.

GSK also confirmed the discontinuation of two additional research programs: a mid-stage Ebola drug that has been “transferred to the Sabin Vaccine Institute,” and GSK2292767, a PI3Kδ inhibitor currently undergoing Phase 1 clinical trials for respiratory diseases.

RIP1 Kinase Inhibitors Have Garnered R&D Interest in the Biotechnology Sector, Particularly in Central Nervous System and Inflammatory Disease Research. Last year, Sanofi acquired two RIP1 inhibitors under development by Denali Therapeutics for $125 million, including DNL747. This drug is currently undergoing Phase 1 studies for amyotrophic lateral sclerosis (ALS), and Denali’s scientists believe that inhibiting RIP1 can prevent the production of inflammatory molecules in the body. Sanofi and Denali are also advancing research on several other compounds, including DNL758, a peripherally acting RIP1 inhibitor (without blood-brain barrier penetration) intended for systemic inflammatory diseases.

Reference: GlaxoSmithKline's RIPK1 Inhibitor Dead on Arrival