Dewpoint Therapeutics is a biotechnology company pioneering a new approach to drug discovery. The company aims to develop a new generation of medicines by translating breakthroughs in how cellular components organize themselves. This involves leveraging biological insights to address a wide range of diseases that currently lack effective treatments.
The Science of Biomolecular Condensates
Cells contain highly organized structures that perform specialized tasks. While many of these structures, like the nucleus or mitochondria, are membrane-enclosed, a distinct class of cellular compartments exists without such boundaries. These are known as biomolecular condensates, or membraneless organelles. They are dynamic, liquid-like droplets composed primarily of proteins and nucleic acids, which can form and dissolve rapidly within the cell.
The formation of these condensates is governed by liquid-liquid phase separation (LLPS). This process is similar to how oil and water separate into distinct layers. Certain proteins and RNA molecules in the cell’s watery environment spontaneously demix, concentrating themselves into dense, droplet-like regions. This separation is driven by numerous weak, transient interactions between multivalent molecules.
These interactions allow condensates to remain fluid and adaptable, rather than forming rigid structures. Their dynamic nature provides cells with a mechanism to quickly assemble or disassemble these compartments. This occurs in response to changing environmental conditions or specific cellular needs, such as stress or nutrient availability.
In healthy cells, biomolecular condensates serve various functions. They act as organizational hubs for biochemical reactions, concentrating specific molecules like enzymes and their substrates. This enhances the efficiency of cellular processes such as RNA metabolism, gene expression, and signal transduction. These microenvironments accelerate reaction rates, regulate molecular activity, and organize larger cellular structures. They also play roles in stress responses and DNA repair, showcasing their broad involvement in maintaining cellular homeostasis.
Condensates and Disease Formation
While biomolecular condensates are beneficial for cellular function, their balance can be disrupted, leading to disease. Dysregulation of liquid-liquid phase separation or changes in condensate material state can impact cell health. This dysfunction can include condensates failing to form, failing to dissolve, or transitioning from a liquid-like state to a more solid, toxic aggregate.
Such aberrant condensate behavior is linked to various pathological conditions. In neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), Alzheimer’s disease, and Parkinson’s disease, proteins such as TDP-43, FUS, Tau, and alpha-synuclein can misfold and aggregate. These proteins often form initial liquid-like condensates that, under stress or due to genetic mutations, transition into irreversible, stiff, and insoluble aggregates. This hardening can lead to loss of normal protein function and accumulation of toxic inclusions within neurons, contributing to cellular dysfunction and death.
Dysfunctional condensates are also implicated in various types of cancer. Changes in condensate formation or regulation can disrupt gene expression, leading to uncontrolled cell proliferation. For example, mutations in proteins like Speckle-Type POZ Protein (SPOP) have been linked to solid tumors. These mutations can alter normal function and contribute to cancer development. Understanding these pathological transitions provides new avenues for therapeutic intervention.
Dewpoint’s Drug Discovery Platform
Dewpoint Therapeutics employs a unique and integrated approach to drug discovery, designed to identify therapies that modify biomolecular condensates. Their proprietary platform, ERSA, is powered by an artificial intelligence and machine learning engine known as ERSAi. This technology allows Dewpoint to explore relationships between condensates, human disease, and chemical compounds, accelerating drug discovery.
The ERSA platform supports a four-pillar approach: target discovery, condensate-modulating drug (c-mod) discovery, c-mod optimization, and c-mod development. Dewpoint uses cutting-edge high-content imaging and AI-driven image analysis to visualize biomolecular condensates within living cells. This allows observation of how condensate properties are altered in disease states, providing a precise readout.
Through this screening process, Dewpoint identifies compounds that can selectively engage with and restore normal condensate function. These “condensate-modifying drugs,” or c-mods, represent a novel class of therapeutic agents. They are designed to act by unique mechanisms. These include dissolving harmful solid aggregates, promoting beneficial condensate formation, or altering their dynamic properties to reinstate cellular balance.
The platform measures how a compound partitions into a target condensate, allowing for selective targeting of specific molecules within these structures. This significant advancement, combining condensate biology expertise with experimental technologies and a chemical library, enables Dewpoint to tackle previously “undruggable” targets and accelerate the translation of condensate science into new medicines.
Therapeutic Pipeline and Collaborations
Dewpoint Therapeutics is translating its robust therapeutic pipeline aimed at diseases with high unmet medical needs. The company’s pipeline includes over 20 development programs, spanning oncology, neurodegeneration, cardiopulmonary disorders, and virology. This targets conditions where dysfunctional condensates play a causative role.
In oncology, Dewpoint has nominated two development candidates, DPTX3186 and DPTX3496. These orally administered small molecule c-mods target Wnt-driven cancers by inhibiting beta catenin. They work by sequestering beta catenin into nuclear depot condensates, which downregulates related genes and kills tumor cells. DPTX3186 anticipates filing an Investigational New Drug (IND) application in mid-2025, with Phase 1 clinical trials expected in the second half of 2025. DPTX3496, also a beta catenin c-mod, is undergoing IND-enabling studies for colorectal, breast, and lung cancers, with an IND filing planned for the second half of 2025.
For neurodegeneration, Dewpoint is advancing a TDP-43 small molecule c-mod for Amyotrophic Lateral Sclerosis (ALS), in collaboration with Mitsubishi Tanabe Pharma. The company has also established collaborations with Bayer for cardiovascular and renal diseases, Novo Nordisk for insulin resistance and diabetic complications, and Merck for HIV therapeutics. A partnership with Pfizer targets myotonic dystrophy type 1. These alliances accelerate Dewpoint’s efforts to bring condensate biology-based treatments to patients.