Dewpoint Therapeutics Nominates First C-Mod Candidate DPTX3186 for Wnt-Driven Cancers

On October 28, 2024, Dewpoint Therapeutics Inc., a prominent biotechnology firm specializing in the development of therapeutics targeting biomolecular condensates, announced the nomination of its first development candidate, DPTX3186. This candidate is an orally administered small molecule condensate modulator (c-mod) designed to inhibit the oncogenic activity of beta catenin, aimed at treating cancers driven by the Wnt signaling pathway. The discovery was made through Dewpoint’s sophisticated platform, which integrates artificial intelligence and machine learning with an extensive proprietary chemical library.

Beta catenin is a crucial transcription factor within the Wnt signaling pathway, essential for various physiological processes in healthy cells. However, its aberrant activation is linked to carcinogenesis and tumor progression in several cancer types, including colorectal, gastrointestinal, non-small cell lung, breast, and liver cancers. Traditionally, targeting beta catenin has been challenging due to its disordered regions and lack of suitable drug-binding pockets, leading to difficulties in drug development often marked by toxicity and off-target effects.

DPTX3186 operates through a unique mechanism by sequestering beta catenin into nuclear depot condensates, which downregulates beta catenin-related genes, effectively killing tumor cells. This small molecule c-mod shows activity across various beta catenin/Wnt-driven tumor cell types and exhibits minimal toxicity in healthy cells. In patient-derived and cell-derived xenograft models, DPTX3186 has shown significant tumor growth inhibition, stasis, and regression.

Ameet Nathwani, CEO of Dewpoint Therapeutics, emphasized the importance of this milestone, noting that the nomination of DPTX3186 highlights the transformative potential of their advanced platform when combined with a novel approach to condensate science. This achievement underscores their commitment to addressing diseases with high unmet needs by identifying and advancing a new class of therapeutic agents. Nathwani further mentioned that DPTX3186 has demonstrated substantial activity in preclinical models, selective targeting of tumor cells, and a specific mechanism of action on the beta catenin/Wnt pathway.

To expedite the development of DPTX3186, Dewpoint has partnered with Evotec. This collaboration will utilize Evotec’s INDiGO platform to rapidly generate a high-quality Investigational New Drug (IND)-enabling package. The IND filing is anticipated in mid-2025, with the initiation of Phase 1 clinical trials expected in the second half of 2025.

Dewpoint Therapeutics leads the field in applying biomolecular condensate biology to develop new therapeutics for diseases with significant unmet needs. The understanding that many conditions are regulated by or result from condensate dysfunction has opened new avenues for targeting high-value but previously deemed undruggable targets. Dewpoint’s proprietary platform, powered by AI and machine learning, supports a diverse drug discovery pipeline encompassing oncology, neurodegenerative, cardiopulmonary, and metabolic diseases. Collaborations with major entities like Bayer, Novo Nordisk, and Evotec enhance their ability to translate condensate biology into effective treatments for patients with hard-to-treat diseases.