Could a little-known organelle be the key to new treatments for neurodegenerative diseases? Apple Tree Partners is betting $50 million on it, creating Nereid Therapeutics with Princeton University biophysicist Clifford Brangwynne, Ph.D., to drug those organelles.
Known as biomolecular condensates, these membraneless organelles form when liquids in the cell separate from the cell’s cytoplasm—think bubbles in a lava lamp or oil droplets in salad dressing. They’re a key component to understanding how cells function and misfunction.
“When that process goes awry, that’s associated with disease,” said Brangwynne, a pioneer in the condensates field and chair of Nereid's scientific advisory board.
Brangwynne and his peers have long known about condensates, but they have been historically difficult to study.
“There have not been ways to quantitatively interrogate what's happening in cells, the underlying physical forces that are at play in organizing a cell and forming a healthy cell with healthy structures, and understanding how that process goes wrong,” Brangwynne said.
Nereid’s drug discovery platform is based on tech out of Brangwynne’s lab that solves that problem, allowing the precise measurement, interrogation and control of phase separation—the process through which condensates form—in mammalian cells.
This quantitative approach has previously been out of reach for scientists studying the physics of cell movement, and it's especially useful for speeding up early drug development, said Spiros Liras, a venture partner at Apple Tree Partners and interim CEO of Nereid.
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The company plans to develop treatments for neurodegenerative diseases, as well as other diseases such as fibrosis and certain cancers.
In the case of illnesses caused by protein aggregation, like amyotrophic lateral sclerosis (ALS), Huntington and Alzheimer's disease, “the reason why we have no treatments for these diseases is that there has not been a fundamental understanding of the thermodynamics, the molecular interaction landscape that drives assembly," Brangwynne said, referring to the process by which cells build proteins.
Nereid’s platform allows researchers to extract a “fingerprint” of the interactions happening in the cells. Understanding that fingerprint will help Nereid figure out how to tweak it, with the hope of moving cells away from disease-causing processes.
The company is already fielding interest from potential partners, which Brangwynne attributes to a growing interest in biomolecular condensates. Dewpoint Therapeutics, another condensates biotech, launched in early 2019 and has since struck a $305 million deal with Merck on HIV treatments and inked a $100 million pact with Bayer on heart disease and women’s health.
“All of a sudden, you see papers, left and right, talking about material properties of condensates, and viscosity and surface tension,” Brangwynne said of new papers by biologists. “A few years ago, the same biologist never heard of those terms. So I think that's really exciting.”
Editor's note: This story has been updated to clarify that targeting condensates could be used to treat diseases like ALS, Alzheimer's and Huntington disease, but that Nereid has not disclosed the indications it is pursuing beyond "certain cancers and neurodegenerative disorders."