The milestones keep coming as Dewpoint approaches ‘inflection point’

The recent news flow at Dewpoint Therapeutics—the firm making condensate biology a clinical reality—has been striking in its volume and significance.

Condensate biology reflects a new understanding of cell biology, with broad implications for disease understanding and drug development. Biomolecular condensates compartmentalize and spatially regulate biological processes in healthy cells. When they malfunction, they are at the root cause of complex diseases, and they can be corrected with small molecule drugs called condensate modulators.

Dewpoint is a clinical-stage biotech that has only been around for seven years, but the outstanding scientific foundations on which the Boston company is based—coupled with plenty of hard work since—have led to a flurry of milestones in the past few months.

Isaac Klein, Dewpoint’s Chief Scientific Officer and Ann Boija, the company’s SVP and Head of Research, spoke to The Pharma Letter about the scientific and strategic advances driving the company’s recent momentum.

‘Holy grail oncology targets’

The most recent milestone was Dewpoint’s selection of a first-in-class MYC condensate modulator development candidate (DC).

MYC is a master regulator of oncogenic transcription implicated across multiple high-burden cancers, yet has historically resisted pharmacologic control despite decades of effort across biopharma. Dewpoint’s MYC DC is an orally-delivered small molecule designed to selectively disrupt MYC-driven oncogenic transcription by modulating the aberrant biomolecular condensates that organize its activity in cancer cells.

The candidate was selected based on a comprehensive preclinical data package demonstrating potency and specificity in MYC-dependent cellular systems, favorable in vivo pharmacology, including tumor regressions in MYC-dependent models, and tolerability supportive of advancement into IND-enabling studies.

This program is positioned to explore multiple tumor contexts in which MYC dependence is a central driver of cancer biology.

The first candidate that Dewpoint declared in oncology, DPTX3186 targeting beta-catenin condensates, is being studied in a Phase Ia/IIa trial in advanced solid tumors, with a focus on gastric cancer, with both FDA orphan drug and fast track designations.

Dr Boija explained how advances in condensate biology are opening new ways to target proteins long considered challenging to drug. 

“Both MYC and beta catenin are widely regarded as ‘holy grail’ oncology targets," she said. "They have proven extremely difficult to drug because they lack well-defined small-molecule binding pockets, and because directly inhibiting them risks significant toxicity.

“What has changed is our understanding of how these proteins function in the cells. MYC and beta-catenin don't act as isolated molecules - they operate within the biomolecular condensates that organize the transcriptional machinery. When we shift our focus from the individual protein to the condensates as the functional unit of biology, entirely new therapeutic opportunities emerge.”

Dr Boija said this deeper understanding of condensate biology now enables Dewpoint to systematically pursue transcriptional drivers that have historically resisted conventional drug discovery approaches.

A ‘transformative moment’ for patients

Also announced of late was the selection of a DC for Dewpoint’s TDP-43 program. It is a first-in-class small molecule designed to correct disease-associated TDP-43 condensates, restoring normal TDP-43 function genome-wide and addressing the core molecular pathology that drives neurodegeneration in amyotrophic lateral sclerosis (ALS). The candidate has demonstrated in vivo activity in multiple animal models with clinically validated biomarker readouts.

Dr Boija said: “We have known for several years that TDP-43 loss-of-function lies at the heart of ALS pathology, but a drug to correct this has been elusive. We have deciphered the molecular cause of this loss of function – a dysfunctional condensate – and designed a molecule specifically to address it.”

She added: “It's an extraordinary time, being in the clinic with the first condensate modulator for Wnt-driven cancers, and having DCs for MYC and TDP-43 coming behind it. We are approaching a transformative moment for our company and the field of condensate biology.”

‘Great feedback’ from partners and steady progress in the clinic

No wonder then, that Dewpoint has interest from investors and big pharma wanting to be part of the story. A Series D round was the latest to be announced in September. Dewpoint has also announced a licensing deal with Bayer (BAYN: DE), as well as partnerships with Novo Nordisk (NOV: N) in insulin resistance, and with the Gates Foundation in HPV-driven cancers.

“We’ve had great feedback from our partners,” Dr Klein said, though he is confident that the best is yet to come as Dewpoint starts to share clinical data from its lead asset over the next year.

“That's the kind of data that drives an IPO,” he said. “Across our portfolio, we have a steady cadence of milestones and data ahead. In our view, Dewpoint is approaching an inflection point, for the company, for patients, and for the entire condensate biology field.”