Major milestone for Dewpoint with first development candidate announced

Dewpoint Therapeutics, a US biotech focused on the application of biomolecular condensate biology, has announced the nomination of its first development candidate, DPTX3186.

This orally-administered small molecule condensate modulator (c-mod) inhibiting the oncogenic function of beta catenin, is being developed as a potential therapeutic agent for treatment of Wnt-driven cancers.

DPTX3186 was discovered using Dewpoint’s fully automated, AI/ML-enabled platform and proprietary chemical library. It is being developed in collaboration with Germany’s Evotec (FSE: EVT/Nasdaq: EVO).

Target often deemed undruggable

According to Dewpoint, beta catenin is a key transcription factor in the Wnt signaling pathway, which plays a crucial role in various physiological processes in healthy cells.

Aberrant activation of beta catenin, as part of constitutively active transcriptional condensates, is associated with carcinogenesis and tumor progression in colorectal cancer, gastrointestinal cancer, non-small cell lung cancer, breast cancer, liver cancer, and other types of cancers.

Beta catenin is often seen as an undruggable target, due to the presence of disordered regions and structural features lacking suitable drug binding pockets.

Historically, the development of beta catenin therapies has been frequently hindered by toxicity and off-target effects.  

DPTX3186 acts through a novel mechanism of action to sequester beta catenin into nuclear depot condensates. This sequestration leads to downregulation of beta catenin related genes, resulting in significant tumor cell killing.

As well as demonstrating activity across various beta catenin/Wnt-driven tumor cell types, DPTX3186 exhibits minimal toxicity in healthy cells. In patient-derived and cell-derived xenograft models, it displays significant tumor growth inhibition, including regression and tumor stasis.  

Transformative potential

Ameet Nathwani, chief executive of Dewpoint, said: “Nominating this development candidate marks a significant milestone in our journey to deliver the first condensate modulating drug to the clinic.

“The discovery and selection of DPTX3186 for a target considered ‘undruggable’ underscores the transformative potential of our state-of-the-art platform combined with a fresh perspective on the underlying biology, through the lens of condensate science.

“This approach enabled us to identify and advance a novel class of therapeutic agents to address diseases of high unmet need. To date, DPTX3186 has demonstrated significant activity in preclinical models across multiple types of cancer, high selectivity for tumor cells, and a mechanism of action on the beta catenin/Wnt pathway.

“To accelerate the development of DPTX3186, we partnered with Evotec. Together, we will leverage Evotec’s INDiGO platform for the rapid and efficient generation of a high-quality IND-enabling package.”

Dewpoint anticipates filling the IND in mid-2025, followed by the start of Phase I clinical trial in the second half of the year. 

DPTX3186 is one of Dewpoint’s wholly-owned programs. The company’s diversified portfolio is composed of wholly-owned programs in oncology and neurodegeneration, and partnered programs in cardiovascular diseases – with German company Bayer (BAYN: DE), and metabolic diseases – with Danish pharma major Novo Nordisk (NOVN: VX).