CAMBRIDGE, Mass. — Casma Therapeutics has nominated its first drug development candidate, CSM-101, for the treatment of Parkinson’s disease and related neurodegenerative disorders, the company announced Thursday. The experimental therapy, a first-in-class TRPML1 agonist, is designed to restore lysosomal function—a key factor in both rare and common forms of the disease.
Initially targeting patients with Gaucher’s disease who develop Parkinson’s (GD-PD), Casma also sees potential for expanding CSM-101’s use to broader Parkinson’s populations, including those with GBA mutations (GBA-PD) and idiopathic Parkinson’s disease. The company will present supporting preclinical data at the GBA1 Meeting 2025 in Montreal, held June 5–7.
“This is a major milestone for Casma and the field,” said Frank Gentile, Ph.D., CEO of Casma Therapeutics. “Our preclinical results show that TRPML1 activation effectively addresses lysosomal dysfunction, a central driver in neurodegeneration.”
CSM-101 is an orally bioavailable small molecule that activates TRPML1, a key lysosomal ion channel. In lab studies, the drug showed high brain exposure and therapeutic effects across models of Gaucher’s and Parkinson’s disease, including reductions in toxic lipid accumulation, neuroinflammation, and alpha-synuclein levels. The treatment also preserved dopamine-producing neurons and improved survival rates in animal models, according to the company.
Leon Murphy, Ph.D., Chief Scientific Officer at Casma, emphasized the therapeutic’s targeted approach. “CSM-101 offers a scientifically validated path to restoring lysosomal function. Our strategy focuses on genetically defined patient populations and robust biomarkers to accelerate clinical validation.”
Casma plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration in the first half of 2026.
