Biomolecular condensates find the investment spotlight

Biomolecular condensates—droplets of proteins and RNA that coalesce and then quickly disappear from the cytoplasm of our cells—are having a moment. Faze Medicines is the third company to launch in the past month with a focus on the drug discovery opportunities of this emerging biology. It raised $81 million in series A funding, led by Third Rock Ventures.

Just weeks before, Nereid Therapeutics launched with $50 million in funding, and Transition Bio debuted with undisclosed seed funding. Dewpoint Therapeutics, a condensate forerunner, has inked deals with two large pharmaceutical partners since its launch in 2019.

“It’s really great to have so many people in this space,” says Rachel Meyers, Faze’s chief scientific officer. “It validates the importance of it.”

Biomolecular condensates are often compared to the blobs of shapeshifting wax in lava lamps. Clusters of proteins and RNA can form short-lived, membraneless organelles through a process called liquid-liquid phase separation. They seemingly appear out of nowhere before dissolving back into the cytoplasm.

Once a neglected biological phenomenon, condensates started attracting attention about a decade ago. In 2012, for example, Faze cofounder and University of Texas Southwestern Medical Center biochemist Michael Rosen explored their biophysical properties in a key Nature paper (Nature 2012, DOI: 10.1038/nature10879). From the beginning, it seemed possible that these transient droplets might serve as cellular reaction vessels: speeding reactions up by concentrating reactants or slowing them down by keeping reactants apart. More recently, researchers have been unraveling their biological role in both health and disease.

“What’s becoming clearer is what these biocondensates are doing, how they are doing it, and how they are regulated,” Meyers says.

Faze is focusing on applications in neurodegenerative disease. Some mutations associated with amyotrophic lateral sclerosis (ALS) seem to make condensates “sticky” and prone to hang around, and this might drive disease pathology. Small-molecule drugs that reverse this stickiness may hold promise for ALS patients.

Faze has yet to disclose specific drug targets. But the condensate constituents as well as the molecular machinery that controls condensate biology are potential options.

Faze is also working on drugs for myotonic dystrophy type 1, a neuromuscular disorder. “Those seemed like obvious places for us to embark on this exploration. But I think it’s pretty clear that many, many, many other opportunities will emerge,” Meyers says.

Dewpoint and Nereid are also working on neurodegenerative conditions, as well as on cancer applications.

In the short-term, all of these companies hope to reverse harmful condensate biology. As they learn to control condensate composition and behavior, however, they might tackle so-called undruggable targets as well. Rather than inhibit such a target directly, a drug might help lock it up in a condensate. “Condensates allow us to think about drug discovery in a different way,” says Spiros Liras, cofounder and interim CEO of Nereid. This opportunity has contributed to the explosion of interest in this space, he adds.

Bigger drug firms are watching. Dewpoint has already partnered with Bayer on cardiovascular and gynecological diseases and with Merck & Co. on HIV.

Faze plans to partner with large firms as well, says Cary Pfeffer, interim CEO of the company and partner at Third Rock Ventures. Novartis Venture Fund, Eli Lilly and Company, and AbbVie Ventures all joined the funding syndicate, he points out, highlighting big pharma interest in condensates.

“We are incredibly excited about the transformation in biology that is taking place in front of our eyes,” Pfeffer says.