Human cells are often compared to factories, filled with microscopic machines that transport supplies, remove waste, generate energy and guard against intruders.
Though much is known about how these factories work, many parts remain mysterious. Scientists have long noticed, for example, that certain proteins and molecules cluster together to form tiny droplets, they just didn't have many clues as to why.
That was, until recent studies suggested the clusters — now called biomolecular condensates — are important tools for regulating cell activities. And if they're incorrectly put together, the thinking is they may malfunction and give rise to a variety of diseases, from ALS to cancer.
This research has inspired the formation of several new drug companies in the last couple years, with the latest, Faze Medicines, debuting Thursday. Faze launches with $81 million in fresh funding, supplied both by powerful venture capital firms and by large pharmaceutical companies.
"This really is a new, big area of biology that has a lot of promise, and there's already a lot of data supporting the direction we're going in," said Cary Pfeffer, a partner at Third Rock Ventures, which has been working on Faze for more than two and a half years and is now leading its new round of funding. Pfeffer will serve as the biotech's interim chief executive officer.
Put simply, biomolecular condensates are liquid-like, concentrated mixtures of RNA, proteins and other molecules that can make cellular activities speed up, slow down or be more efficient. Pfeffer likens them to team meetings in an office.
"They involve different people, they get different things done, and they're not all focused on the same sort of thing," he said. "They also have to come together at the right time and come apart at the right time. And so, in the course of a day, depending on the size of the office, there could be hundreds of these things going on."
There are some important nuances, though, according to Rachel Meyers, Faze's chief scientific officer and an entrepreneur-in-residence at Third Rock.
One is that condensates tend to stay in certain locations, often where they're most useful. Those that process messenger RNA, for example, are frequently in the core part of the cell, where RNA molecules are produced.
Another is that condensates quickly form and break apart based on what's happening around them. Changes in temperature or acidity can affect their structure, as can other stressors.
Notable, too, is that condensates form because of specific interactions between specific molecules, and can therefore exclude materials which might compromise their overall structure. The process isn't foolproof, however. Genetic mutations can throw a wrench in the process by impairing some of the proteins and RNA that go into the condensate, which in turn affects its properties.
"They become a little bit less liquid-like and fluid, and a little bit more rigid," Meyers said. "So that mutation leads to a change in a particular amino acid, that leads to a change in the function of a protein, that leads to a change in the properties of this biomolecular condensate, and that then [can cause] disease."
Faze's plan is to dissect some of these condensates, figure out which pieces are most crucial to their structure, and then develop small-molecule drugs that target either the pieces themselves or the pathways that regulate them. The biotech has initially set its sights on discovering treatments for ALS, or amyotrophic lateral sclerosis, as well as a neuromuscular disorder called myotonic dystrophy type 1.
Pfeffer said other neurological and neurodegenerative disorders could come onto Faze's radar too, as could cancer, immune diseases and viral illnesses.
With its debut, Faze joins a rapidly growing crop of young biotechs focused on this emerging research field. Dewpoint Therapeutics was the first to come out of stealth mode, arriving in early 2019 with $60 million in Series A financing. The Boston-based company has since caught the attention of pharma giants Bayer and Merck & Co., inking separate deals potentially worth $100 million or more.
Then, last month, Transition Bio and Nereid Therapeutics joined the fray.
Meyers thinks this bourgeoning interest is closely tied to the excitement that in recent years engulfed RNA therapeutics — a field Meyers knows intimately, having served in various research leadership positions at Alnylam Pharmaceuticals for more than a decade.
"It's a very hot space," Meyers said of biomolecular condensates. "You have interesting biology driving interesting processes, linked to important diseases."
In addition to Third Rock, Faze's Series A financing saw investments from the Novartis Venture Fund, Eli Lilly, AbbVie Ventures, Invus, Catalio Capital Management, Casdin Capital and Alexandria Venture Investments.
Faze currently has around a dozen employees, and Pfeffer expects that number to increase to roughly 25 to 30 by the end of 2021, with most roles focused on research.
The latest fundraising round should be enough to fuel the company for at least a few years, he added, though there's "no question" that Faze will eventually need more capital once it hits certain early milestones. Pfeffer said partnerships are "certainly" being considered as part of Faze's strategy.
"We've seen an incredible amount of interest on the pharma side, even before launching the company," he said.