Casma Therapeutics Nominates CSM-101 as a Development Candidate for the Treatment of Rare and Common Forms of Parkinson’s Disease

Casma Therapeutics, Inc., a biotechnology company engaging the autophagy and lysosomal systems to develop innovative new medicines, today announced the nomination of its first development candidate, CSM-101, a first-in-class TRPML1 agonist. CSM-101 is being developed for the treatment of Gaucher’s disease patients with Parkinson's disease (GD-PD), with the potential to expand into GBA-associated Parkinson’s disease (GBA-PD) and broader Parkinson’s disease (PD) populations. The company will share preclinical data supporting the progression of CSM-101 into IND-enabling studies in an oral presentation at the GBA1 Meeting 2025, taking place June 5-7 in Montreal, Canada.

"Our nomination of CSM-101 marks a major milestone for Casma and the field as we translate our deep expertise in autophagy and lysosomal biology into therapeutic candidates," said Frank Gentile, Ph.D., Chief Executive Officer of Casma Therapeutics. "Our preclinical data demonstrate that activating TRPML1 effectively addresses lysosomal dysfunction, a central driver in both rare and prevalent neurodegenerative diseases."

CSM-101 is a highly differentiated, orally bioavailable small molecule that restores lysosomal function by activating TRPML1, a critical lysosomal ion channel. In preclinical studies, CSM-101 demonstrated high CNS exposure, potent activity across clinically relevant models, significant reductions in toxic lipid levels, decreased neuroinflammation, and improved survival in multiple Gaucher’s disease models. In GBA-associated Parkinson’s disease and idiopathic Parkinson’s disease models, CSM-101 reversed a pathological phenotype, lowered toxic alpha-synuclein levels and preserved dopaminergic neurons, supporting its potential as a disease-modifying therapy. These data, combined with favorable pharmacokinetic and safety profiles, provide strong translational rationale for clinical development.

"CSM-101 represents a scientifically validated and targeted approach to restoring lysosomal function through TRPML1 activation, addressing a central driver of disease progression in Gaucher’s disease and Parkinson’s disease," said Leon Murphy, Ph.D., Chief Scientific Officer of Casma Therapeutics. "By focusing first on genetically defined patient populations and leveraging robust biomarkers, we are positioned to deliver rapid clinical proof of concept with the potential for meaningful benefits for patients."

Casma plans to file an Investigational New Drug (IND) application with the US FDA for CSM-101 in the first half of 2026.

About TRPML1

TRPML1 is a lysosomal ion channel that regulates critical aspects of lysosomal function, including lysosomal pH and the clearance of cellular waste. Dysfunction of TRPML1 leads to impaired degradation and accumulation of toxic substrates, contributing to the pathology of neurodegenerative and lysosomal storage diseases. Mutations in the GBA1 gene, which cause Gaucher’s disease and are the most common genetic risk factor for Parkinson’s disease, disrupt lysosomal homeostasis. Restoration of TRPML1 activity has been shown to correct lysosomal defects in preclinical models of Gaucher’s disease, GBA-associated Parkinson’s disease, and idiopathic Parkinson’s disease, supporting its potential as a therapeutic target across a range of indications involving lysosomal dysfunction.

About Casma Therapeutics

Built on deep expertise in cellular degradation biology, Casma Therapeutics is advancing targeted therapies that engage the lysosomal or autophagy systems to selectively degrade disease targets and halt or reverse disease progression in neurodegeneration, oncology, inflammation, and metabolic disorders. Casma’s first-in-class TRPML1 agonist restores lysosomal function to treat Gaucher's disease patients with Parkinson's disease, and is poised to expand into GBA-associated Parkinson’s disease and idiopathic Parkinson’s disease. Casma’s PHLYT™ degrader platform is unlocking new therapeutic possibilities through selective autophagy-targeted degradation of large, complex disease targets such as organelles, protein aggregates, and signaling complexes. Casma is based in Boston, Massachusetts. For more info, visit www.casmatx.com.

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