RARE Daily

Dewpoint Restructures, Gets Target ALS Foundation Grant

January 17, 2024

Rare Daily Staff

Dewpoint Therapeutics cut 15 percent of its staff as part of a restructuring after collaborations with two pharmaceutical companies ended, STAT News reported.

Separately, the company announced Target ALS Foundation awarded it a grant, in collaboration with the ALS Association and The Jackson Laboratory, for an in vivo proof-of-concept study for a treatment for the most common form of the genetic, neurodegenerative disease ALS.

Ameet Nathwani, CEO of Dewpoint, told STAT the reductions were temporary as the company retools its roster and hires employees with needed expertise to advance its experimental therapies into the clinic and expand its AI capabilities.

Pfizer in 2023 ended a myotonic dystrophy type 1 partnership with Dewpoint in 2023 as part of its step back from rare neurological diseases. Merck also ended its partnership with the company focused on HIV.

Dewpoint is applying the emerging understanding of biomolecular condensates to drug discovery for a wide range of conditions. Condensates are membraneless organelles that form dynamically throughout the cell via a process called phase separation. These subcellular compartments organize and concentrate molecules within cells to enable certain key biochemical processes. The dysregulation of biomolecular condensates has been observed in many diseases, including cancer, diabetes, and neurological disorders. Condensate-modifying drugs (c-mods) potentially provide novel therapeutic options for complex diseases and historically undruggable targets.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that accounts for up to 20,000 patients in the U.S. each year with a patient life expectancy of a mere two to five years. Challenges to develop effective therapeutics for ALS stem, in part, from the diverse, and poorly understood genetic background of the patients. Only about 10 percent of the patients have a genetically inherited defect associated with ALS while the remaining roughly 90 percent of the cases are sporadic and can be traced to a combination of genetic and environmental factors.

Dewpoint leverages an aberration that occurs in about 97 percent of all ALS patients – independent of genetic background – to drive the discovery and development of a new, and potentially more effective class of therapeutics. This common aberration – termed condensatopathy – is the incorrect localization of the TDP-43 protein from the nucleus into cytoplasmic condensates. TDP-43 condensatopathy is a central node of dysfunction in ALS and it is strongly correlated with multiple functional and physiological markers of the disease.

The Target ALS Foundation grant will fund an in vivo proof-of-concept study of condensate-modifying drugs in a chronic C9orf72 repeat, the most common genetic cause of ALS. Dewpoint discovered small molecules that re-locate TDP-43 from the aberrant cytoplasmic condensates into the nucleus, and consequently rescue systemic defects in transcription, splicing, and markers of neuronal health.

“This grant will propel our research efforts and accelerate the development of our ALS-targeted c-mods towards becoming the first molecules to address the underlying pathology in most ALS patients,” said Ameet Nathwani, CEO of Dewpoint Therapeutics.

Photo: Ameet Nathwani, CEO of Dewpoint

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