Dewpoint Therapeutics

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Who leads Dewpoint Therapeutics?

Dewpoint was founded in 2018 to develop new medicines against biomolecular condensates. The two founders are Anthony Hyman and Richard Young:

• Hyman is a professor at the Max Planck Institute of Molecular Cell Biology and Genetics. His research is focused around biomolecular condensates and phase separation in cells. 

• Young is a professor at MIT. His research pioneered systems biology and used this toolkit to also study condensates. He also co-founded Syros Pharmaceuticals and CAMP4 Therapeutics, which focused on drugging gene expression.

What does Dewpoint Therapeutics do?

Biomolecular condensates are compartments found in eukaryotic cells that are composed of proteins and nucleic acids and whose organization is driven by liquid-liquid phase separations. They have been discovered recently to be involved in ribosome biogenesis, the DNA damage response, RNA metabolism, among other pathways. The premise is that condensates drive the formation of active and inactive regions of the genome and selectively partition certain proteins.

By focusing on this emerging field of biology, Dewpoint is building a unique platform to characterize and drug these condensates:

1. Gene expression - condensates are thought to phase separate at certain genomic loci and promote interactions that either increase or decrease gene expression

2. Selective partitioning - condensates are also thought to impact the PK/PD of drugs and certain proteins that are considered undruggable

Dewpoint is building the physical toolkit to understand these 2 parts of biomolecule condensates that can build a knowledge base for drug development. The company, along with the research labs that form Dewpoint’s basis, are working to understand the composition, assembly principles, and other biochemical/physical properties of these cellular structures.

What makes Dewpoint Therapeutics unique?

Dewpoint’s focus on condensates makes the company unique. An emerging field in biology creates an opportunity for a landgrab similar to Alnylam & RNAi, and Moderna & mRNA. Condensates are involved in a wide-range of diseases from neurodegeneration to cancer, metabolic diseases, and rare genetic disorders. In particular, the focus on drugging condensates opens up opportunities to pursue indications and targets that are still considered undruggable.

The key theme for Dewpoint is: “biology meeting physics.” This means the company has to develop and implement new tools to study condensates. Eikon is doing something similar with super-resolution microscopy. Dewpoint is relying on a wide-range of tools to develop new medicines:

• Cross-linking mass spectrometry study how single amino acid change condensate components and overall structure

• Optogenetic tools to control condensate formation inside the cell. “You don’t understand something until you can control it.”

• New types of microscopy to assess the physical state of condensates overtime

• High-content imaging to monitor condensates and screen for drug candidates

The goal of this work is to identify drug-like molecules that perturb condensates. This can be done through direct interactions with proteins and nucleic acids that form these structures or targeting proteins upstream like ATPases and ubiquitinases.

Why I like what Dewpoint Therapeutics is doing?

Dewpoint is building a platform centered around biophysics and a new area of biology, condensates, to bring new medicines to patients. Third Rock’s Faze Medicines is a recent comparable. The next few years will not only show the potential of condensates in human health but answer a few outstanding questions in the field:

• For undruggable targets, do nuclear condensates affect their function?

• Does the diffusion of drugs into condensates had significant effects in past trials?

• Does a target’s temporary transient interactions with biomolecular condensates affect the given target’s function?

• Can drug candidates perturbing condensates formation and (dis)assembly have unintended effects? What are they?

You can find Dewpoint Therapeutics here.