Funding supports IND-enabling activities for Casma’s CSM-101, a first-in-class TRPML1 agonist targeting lysosomal dysfunction in genetically driven neurodegenerative diseases
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Casma Therapeutics, Inc., a biotechnology company engaging the autophagy and lysosomal systems to develop innovative new medicines, today announced that it has been awarded approximately $7.6 million in funding across two competitive grant programs from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). The non-dilutive funding supports a fully integrated preclinical development strategy for Casma’s lead program, CSM-101, enabling the company to generate new TRPML1 biomarker and IND-enabling data required to advance into first-in-human clinical studies.
Casma’s lead molecule, CSM-101, is a highly differentiated, orally bioavailable, CNS-penetrant, small molecule designed to restore lysosomal function by activating TRPML1, a critical lysosomal ion channel. TRPML1 has emerged as a research target of interest in Parkinson’s disease due to its role in lysosomal biology and functional evidence implicating lysosomal pathways across both rare and common forms of the disease.
“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,” said Frank Gentile, Ph.D., Chief Executive Officer of Casma Therapeutics. “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.”
The two grants comprise two complementary MJFF awards spanning late-stage preclinical development for CSM-101. A $2.1 million Targets to Therapies (T2T) grant supports continued validation of TRPML1 biology and the development of translational biomarkers to assess lysosomal activation and inform early clinical decision-making, including dose selection and study design. A $5.5 million Therapeutics Pipeline Program (TPP) grant supports IND-enabling studies required to advance CSM-101 into first-in-human clinical trials. Through its Targets to Therapies (T2T) and Therapeutics Pipeline Program (TPP), MJFF supports complementary efforts to strengthen confidence in disease biology and advance therapeutic programs through key preclinical development stages.
“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,” said Shalini Padmanabhan, Ph.D., Senior Vice President of Discovery and Translational Research at MJFF. “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.”
“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,” said Leon Murphy, Ph.D., Chief Scientific Officer of Casma Therapeutics and the Principal Investigator for both grants. “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.”
Upcoming Data Presentations
Dr. Murphy will present additional data on CSM-101 at two upcoming scientific meetings, in a poster and a talk titled “CSM-101 Is a Brain-Penetrant Small Molecule Agonist of TRPML1 for Parkinson’s-Related Disorders.”
- International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders: poster (SHIFT 02-514) to be available during AD/PD™ 2026 taking place March 17–21 in Copenhagen, Denmark.
- American Academy of Neurology Annual Meeting: podium presentation on Tuesday, April 21 at 1:36 PM CT in Session S26 Movement Disorders: Clinical Trials and Therapeutics. AAN 2026 is taking place April 18–22 in Chicago, Illinois.
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 increase the risk of developing Parkinson’s disease, disrupt lysosomal homeostasis. Enhancing 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 CSM-101
CSM-101 is a highly differentiated, orally bioavailable small molecule that restores lysosomal function by activating TRPML1, a critical lysosomal ion channel. Casma is developing CSM-101 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. 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-PD and idiopathic PD 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 preclinical pharmacokinetic and safety profiles, provide strong translational rationale for clinical development.
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 PHLYTTM 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.
Contacts
Company: Melanie Davis, info@casmatx.com
Media: Jessica Yingling, Ph.D., Little Dog Communications Inc., jessica@litldog.com
