Casma Therapeutics announced that it has received approximately $7.6 million in funding from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to support the advancement of its lead therapeutic candidate, CSM-101. The funding will support late-stage preclinical work and investigational new drug (IND)-enabling studies as the company prepares the therapy for first-in-human clinical trials.
The Cambridge, Massachusetts-based biotechnology company focuses on therapies that target autophagy and lysosomal systems to treat neurodegenerative diseases and other conditions. The new funding will support a fully integrated preclinical development strategy for CSM-101, including the generation of translational biomarkers and other data needed to advance the program into clinical testing.
CSM-101 is designed as a first-in-class, orally bioavailable, brain-penetrant small molecule agonist of TRPML1, a lysosomal ion channel involved in cellular waste clearance and lysosomal function. By activating TRPML1, the therapy aims to restore lysosomal activity, addressing cellular dysfunction associated with Parkinson’s disease and related disorders.
The funding comes from two MJFF grant programs that support different aspects of the drug’s development. The first is a $2.1 million Targets to Therapies grant aimed at strengthening validation of TRPML1 biology and developing translational biomarkers to assess lysosomal activation. These biomarkers are intended to help guide early clinical decision-making, including dose selection and trial design.
The second grant, worth $5.5 million, comes from the foundation’s Therapeutics Pipeline Program and will fund the IND-enabling studies required to move CSM-101 into clinical trials. Together, the two programs support the transition from a deeper biological understanding of the target to preparation for human testing.
TRPML1 has emerged as a promising therapeutic target in Parkinson’s disease because of its role in lysosomal biology and the growing evidence linking lysosomal dysfunction to both rare genetic and common forms of the disease. Dysfunction in lysosomal pathways can lead to the accumulation of toxic cellular materials, which is thought to contribute to neurodegeneration.
Preclinical studies of CSM-101 have demonstrated high central nervous system exposure and activity in disease-relevant models. The therapy reduced toxic lipid levels, lowered neuroinflammation, and improved survival in Gaucher’s disease models. In models of GBA-associated and idiopathic Parkinson’s disease, the therapy also reduced toxic alpha-synuclein levels and preserved dopaminergic neurons, suggesting potential disease-modifying effects.
Casma is initially developing CSM-101 for patients with Gaucher’s disease who develop Parkinson’s disease, with the potential to expand the therapy into broader Parkinson’s populations including GBA-associated and idiopathic forms of the condition.
The company also noted that new data on CSM-101 will be presented at upcoming scientific conferences. These include the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Copenhagen in March 2026 and the American Academy of Neurology Annual Meeting in Chicago in April 2026.
Founded on research in cellular degradation biology, Casma Therapeutics is building a pipeline of therapies designed to engage lysosomal and autophagy pathways to degrade disease-causing targets across areas such as neurodegeneration, oncology, inflammation, and metabolic disorders.
KEY QUOTES
“These awards reflect strong external confidence in both the relevance of TRPML1 as a therapeutic target and our disciplined approach to advancing CSM-101 to the clinic. By supporting translational biomarkers and IND-enabling studies in parallel, this funding allows us to advance CSM-101 toward the clinic with a high level of scientific and regulatory rigor.”
Frank Gentile, Ph.D., Chief Executive Officer of Casma Therapeutics
“The Michael J. Fox Foundation supports research that advances understanding of the biological pathways underlying Parkinson’s disease and translates that knowledge into well-designed therapeutic programs. Through two complementary investments, one focused on strengthening confidence in target biology and biomarker development and another supporting IND-enabling studies, we aim to address key translational gaps and enable more informed evaluation of emerging therapeutic strategies for Parkinson’s disease.”
Shalini Padmanabhan, Ph.D., Senior Vice President of Discovery and Translational Research at The Michael J. Fox Foundation for Parkinson’s Research
“The support from The Michael J. Fox Foundation for these two programs is designed to work together, from deepening our mechanistic understanding of TRPML1 biology to preparing CSM-101 for clinical evaluation. By linking mechanistic understanding of TRPML1 activation with biomarker development and IND-enabling studies, we are establishing the translational foundation needed to evaluate target engagement in patients and advance CSM-101 with confidence in the clinic.”
Leon Murphy, Ph.D., Chief Scientific Officer of Casma Therapeutics and Principal Investigator for Both Grants
