InFlectis OK’d to Start Phase 2 Trial of IFB-088 for Bulbar-onset ALS
The French health authority ANSM has approved InFlectis BioScience’s request to launch a Phase 2 clinical trial testing its lead candidate IFB-088, in combination with riluzole, in people with bulbar-onset amyotrophic lateral sclerosis (ALS).
The trial is expected to be conducted in France and Italy, and a similar request is being reviewed by the Italian Medicines Agency.
“The approval by the ANSM to carry out the Phase 2 clinical study in patients suffering from bulbar-onset ALS with IFB-088 in combination with riluzole is an important step toward developing a new treatment to potentially slow progression of this devastating disease,” Anne Visbecq, MD, InFlectis’ chief medical officer, said in a press release.
IFB-088 is a first-in-class orally available small molecule designed to protect cells from the toxic effects of cellular stress. It does that by prolonging the integrated stress response (ISR), a cellular stress-response mechanism aimed at restoring protein and cellular balance to prevent cell death.
Increasing evidence supports prolonged cellular stress, and a subsequent overwhelmed ISR, as a contributing factor to the accumulation of toxic protein aggregates, or clumps, and the development of neurodegenerative diseases such as ALS.
IFB-088, also known as Sephin1, suppresses the PPP1R15A/PP1c enzymatic complex — which, in turn, maintains an active ISR — specifically in stressed cells, while leaving normal, non-stressed cells unchanged. This is expected to give stressed cells additional time to correct their protein imbalances and eliminate protein clumps.
Notably, guanabenz, another suppressor of the PPP1R15A/PP1c complex, was shown to slow disease progression in adults with early ALS, particularly those with bulbar onset disease, which firstly affects a person’s swallowing, chewing, and speech.
However, the observed high rates of adverse events, such as low blood pressure, and treatment discontinuations in that Phase 2 trial, discouraged further development.
“A similar efficacy is expected for IFB-088 without [blood pressure-lowering] effects,” InFlectis stated in the press release.
The safety of IFB-088’s single and multiple ascending doses, ranging from 2.5 mg to 60 mg per day, was assessed previously in a Phase 1 trial (NCT03610334) involving 72 healthy men.
Results showed that the therapy was generally safe and well-tolerated at all doses, with no reports of serious adverse events, dose-limiting toxicities, or clinically significant abnormalities.
The upcoming Phase 2 trial will evaluate the safety and effectiveness of IFB-088, in combination with riluzole (an approved ALS therapy sold as Rilutek, Tiglutik, or Exservan), in about 42 people with bulbar-onset ALS.
Participants will be assigned randomly to receive an oral capsule of either 50 mg of IFB-088 (28 patients) or a placebo (14 patients), two times a day for six months, in addition to riluzole (100 mg/day).
The therapy’s safety will be monitored over the course of the study by a data and safety monitoring board.