Zydus begins Phase II trial of ZYIL1, NLRP3 inhibitor in patients with ALS

Zydus Life Sciences has received permission from CDSCO, India, to initiate the Phase II clinical study of NLRP3 inhibitor ‘ZYIL1’ in patients with amyotrophic lateral sclerosis (ALS).

ALS patients experience neuroinflammation and rapid neurodegeneration leading to steady loss of the ability to move, speak, eat and eventually breathe. ALS results in loss of motor neurons in the brain and spinal cord which controls voluntary muscle movement.

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. ZYIL1 was found distributed in the brain and CSF of various nonclinical species including mice, rats and non-human primates. The efficacy of ZYIL1 has been established in several validated pre-clinical models of neuroinflammation, Parkinson’s disease, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). The candidate, ZYIL1, has an acceptable ADME profile, with a good safety margin. In Phase I studies, ZYIL1 was found to be safe and well-tolerated [NCT04731324, NCT04972188].

Zydus has 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 Zydus an ‘Orphan Drug Designation’ for ZYIL1 to treat patients with Cryopyrin Associated Periodic Syndrome (CAPS), a rare auto-inflammatory disease.