BOSTON, Massachusetts, January 11, 2024 – Dewpoint Therapeutics Inc., a biotechnology company that translates the novel science of condensates into breakthrough therapeutics, today announced that it was awarded a Target ALS Foundation grant, in collaboration with the ALS Association and The Jackson Laboratory, for an in vivo proof-of-concept study of c-mods in a chronic C9orf72 repeat, the most common genetic cause of ALS.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that accounts for up to 20,000 patients in the US each year with a patient life expectancy of a mere 2-5 years. Challenges to develop effective therapeutics for ALS stem, in part, from the diverse, and poorly understood genetic background of the patients. Only ~10% of the patients have a genetically inherited defect associated with ALS while the remaining ~90% of the cases are sporadic and can be traced to a combination of genetic and environmental factors.
Dewpoint leverages an aberration that occurs in ~97% 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. Condensates are membraneless cellular compartments that regulate, or in this case, dysregulate biological processes. 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. 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.
“Receiving the Target ALS grant is a tremendous honor and a significant validation for Dewpoint’s novel, therapeutic approach to target condensatopathies,” said Ameet Nathwani, CEO of Dewpoint Therapeutics. “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.”
Repeat expansion in the C9orf72 gene is the most prevalent mutation in ALS, explaining about 40% familial and 8% sporadic cases. The in-kind award from Target ALS Foundation will allow Dewpoint to evaluate the in vivo efficacy and mechanism of action of their lead c-mod series in a well-established AAV9-based 149 G4C2 repeat C9orf72 mouse model, using a treatment paradigm over a 3-month period.
Dr. Amy Easton, Sr. Director of Scientific Programs at Target ALS said “Target ALS is excited to fund the generation of in vivo target validation data to support development of Dewpoint Therapeutics’ clinical candidate for ALS. Cellular mislocalization and aggregation of TDP-43 is the pathological hallmark of 97% of ALS cases, however, no marketed drugs target TDP-43 directly. Dewpoint’s study is one of the first to test whether reducing TDP-43 condensates is beneficial in the context of a C9orf72 repeat expansion, the most common genetic cause of ALS. Dewpoint’s research proposal, reviewed by the Target ALS Independent Review Committee, included a high-quality preliminary data package, sufficient to trigger in vivo studies in a disease model.”
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.
ABOUT DEWPOINT THERAPEUTICS
Dewpoint is the first company to apply the emerging understanding of biomolecular condensates to drug discovery for the vast range of conditions that are regulated by condensates or arise from the dysfunction of condensates. Dewpoint drives drug discovery through a proprietary end-to-end experimental and AI-powered platform. Dewpoint currently has programs across an ambitious pipeline spanning oncology, neurodegenerative, cardiopulmonary, and metabolic disease indications, and collaborations with leading global academic and pharmaceutical partners, including Bayer and Novo Nordisk. Dewpoint scientists work in Boston, Dresden, and Frankfurt to translate condensate biology into medicine for diseases previously considered untreatable. Learn more at Dewpointx.com and follow us on X and LinkedIn.
ABOUT TARGET ALS
Target ALS is a 501(c)(3) medical research foundation committed to the search for effective treatments for Amyotrophic Lateral Sclerosis (ALS). Founded in 2013 by former New York City deputy mayor Dan Doctoroff — who lost both his father and uncle to ALS and was himself diagnosed in 2021 – Target ALS has transformed ALS research through their landmark Innovation Ecosystem model. The organization has fostered unprecedented collaborations between academia and the pharma and biotech industry, lowered barriers to access for critical research tools, and become a hub of communication and networking for the worldwide scientific community, resulting in the launch of 7 clinical trials and several drug discovery programs over the last decade. Building upon this momentum, Target ALS launched a groundbreaking Seven Pillar Strategy that will expand the breadth and depth of their ecosystem to accelerate ALS drug discovery with the goal of realizing a world where Everyone Lives. For more information and to get involved, visit www.targetals.org.