Usnoflast: Under development for ALS, PD, IBD and CAPS USFDA fast track designation for ALS and orphan drug designation for ALS and CAPS indications

Usnoflast (ZYIL1) is a novel, oral small molecule NLRP3 inhibitor. Studies have demonstrated that ZYIL1 is highly potent in human whole blood assay and can suppress inflammation caused by the NLRP3 inflammasome. Usnoflast was found distributed in the brain and CSF of various nonclinical species including mice, rats and non-human primates. The efficacy of Usnoflast has been established in several validated pre-clinical models of neuroinflammation, Parkinson’s disease, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). The candidate, Usnoflast, has an acceptable ADME profile, with a good safety margin. In Phase I studies, Usnoflast was found to be safe and well-tolerated [NCT04731324, NCT04972188]. We previously completed a Phase 2(a) randomized, double-blind, placebo controlled clinical trial in 24 ALS patients across 7 clinical trial sites in India. [ClinicalTrials.gov Identifier: NCT05981040] and have recently received approval from USFDA and initiated a randomised, double blind, placebo-controlled Phase 2(b) clinical trial for Usnoflast in patients with Amyotrophic Lateral Sclerosis (ALS). We have completed a Phase 2 clinical study of Usnoflast in Ulcerative Colitis [ClinicalTrials.gov ID NCT06398808] and established the Phase 2 proof-of-concept in CAPS patients [NCT05186051] and has now published the data in Clinical Pharmacology in Drug Development. The USFDA has granted ‘Fast Track Designation’ and ‘Orphan Drug Designation’ for Usnoflast to treat patients with of Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease and an ‘Orphan Drug Designation’ to treat patient with Cryopyrin Associated Periodic Syndrome (CAPS), a rare auto-inflammatory disease.