Dewpoint Therapeutics Reveals New Development Candidate For ALS And Neurodegenerative Diseases, Focused On TDP-43 Condensate Modulation

Dewpoint Therapeutics, Inc., a clinical-stage biotechnology company pioneering condensate-modulating therapeutics, announced the selection of a Development Candidate for its TDP-43 program. This first-in-class small molecule is designed to correct disease-associated TDP-43 condensates, restore normal TDP-43 function, and target the core molecular pathology driving neurodegeneration in amyotrophic lateral sclerosis (ALS) and related disorders.

Pathogenic TDP-43 condensation and dysfunction are observed in the vast majority of ALS cases, affecting more than 97% of patients, and are also implicated in multiple other neurodegenerative conditions. Despite decades of research, TDP-43 has remained largely undruggable using conventional therapeutic approaches. Dewpoint’s condensate biology platform provides a new strategy, enabling the direct modulation of TDP-43 by targeting the abnormal condensate state that underlies its loss of function in disease.

The TDP-43 Development Candidate was selected following extensive preclinical evaluation. The data demonstrate restoration of TDP-43 function in relevant cellular systems, robust efficacy in TDP-43–driven in vivo models of neurodegeneration—including reductions in neurofilament light chain (NfL) levels—clear on-mechanism activity, and pharmacologic properties supportive of progression into IND-enabling studies. The molecule also shows potential applicability across a wider spectrum of TDP-43–associated neurodegenerative disorders, including frontotemporal dementia and traumatic brain injury.

Isaac Klein, M.D., Ph.D., Chief Scientific Officer of Dewpoint Therapeutics, said, “ALS remains one of the most devastating diseases, and pathological TDP-43 condensates are the central driver for the vast majority of patients. This Development Candidate represents the first time full restoration of TDP-43 function has been achieved in preclinical models by directly correcting the pathogenic condensates underlying ALS. We believe this approach has the potential to deliver disease-modifying outcomes for patients.”

Ameet Nathwani, M.D., Chief Executive Officer of Dewpoint Therapeutics, added, “This announcement is more than a program milestone, it validates a novel therapeutic approach and modality that Dewpoint is pursuing. Our condensate biology platform enables direct, mechanistic restoration of TDP-43 function, one of the most important and historically inaccessible targets in neurodegeneration. Advancing this program underscores our belief that condensate-modulating therapeutics can redefine what is achievable in neurology.”

Dewpoint plans to advance the TDP-43 program into IND-enabling studies while continuing to engage closely with the ALS community to guide clinical development strategies and trial design.