Dewpoint Therapeutics Receives Second Target ALS Grant for ALS c-mods Development

Dewpoint Therapeutics Inc., a premier biotechnology firm focusing on the development of drugs targeting biomolecular condensates, has secured a second Target ALS Foundation grant. This grant is aimed at validating Dewpoint's leading condensate-modifying compound (c-mod) in a mouse model of slow-progressing amyotrophic lateral sclerosis (ALS). The initiative is conducted in collaboration with the Biospective contract research organization.

Currently, around 20,000 ALS patients in the United States lack disease-modifying therapeutic options, resulting in a grim prognosis of 2-5 years post-diagnosis. Dewpoint is pursuing a novel approach to ALS drug discovery and development by exploiting a pathology common to over 97% of ALS patients: the mislocalization of the TDP-43 protein from the nucleus to membrane-less cytoplasmic bodies known as biomolecular condensates. This mislocalization impairs TDP-43's splicing function and leads to toxic effects due to the erroneous localization of other proteins into the TDP-43 cytoplasmic condensates. These issues collectively contribute to the systemic defects and complex pathophysiology of ALS.

Dewpoint's leading c-mod was identified through a high-content, high-throughput strategy that selected compounds capable of dissolving the aberrant TDP-43 condensates. Correcting this disease-driving aberrant condensate, or condensatopathy, rectifies systemic TDP-43 loss of function and restores neuronal health. It also improves clinically relevant ALS biomarkers in animal models.

The slow-progressing ALS NLS8 mouse model provided by Biospective and Target ALS mimics the TDP-43 cytoplasmic mislocalization, neurodegeneration, and motor deficits observed in patients. Validating Dewpoint's c-mod in the NLS8 model will enhance the existing data package and ongoing work in a C9orf72 mouse model. This work is supported by another grant from Target ALS and aims to improve understanding of the efficacy, safety, and mechanism of action of this pre-clinical candidate.

Dr. Amy Easton, Senior Director of Scientific Programs at Target ALS, expressed enthusiasm for supporting Dewpoint's mission to develop a novel, effective treatment for ALS patients. She highlighted that Dewpoint's molecule will be among the first to test the central hypothesis regarding TDP-43's role in motor neuron degeneration, with potential implications for both sporadic and familial ALS forms.

Isaac Klein, MD, PhD, Chief Scientific Officer of Dewpoint Therapeutics, also expressed excitement about the expanded partnership with Target ALS. He emphasized the foundation’s efforts to unite academic and biotech communities, which will accelerate the clinical development of Dewpoint’s TDP-43 condensatopathy-targeted c-mod.

Condensates are membraneless organelles that dynamically form within cells via a process called phase separation. These subcellular compartments organize and concentrate molecules to facilitate various key biochemical processes. Dysregulation of biomolecular condensates is implicated in numerous diseases, including cancer, diabetes, and neurological disorders. Condensate-modifying drugs (c-mods) offer potential new therapeutic avenues for complex diseases and targets previously considered undruggable.

Dewpoint Therapeutics leads in applying biomolecular condensate biology to develop new therapeutics for diseases with high unmet needs. The realization that many conditions are governed by or stem from condensate dysfunction has opened new possibilities for targeting high-value, previously deemed undruggable targets. Dewpoint’s AI/ML-powered platform supports a diverse drug discovery pipeline, covering therapeutic areas such as oncology, neurodegenerative, cardiopulmonary, and metabolic diseases. In collaboration with Bayer, Novo Nordisk, and Evotec, Dewpoint aims to translate condensate biology into effective treatments for patients with challenging diseases.

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