A small startup in Watertown has raised millions of dollars for early-stage research on a potentially powerful new idea that’s beginning to take hold in the biotech industry: designing drugs to enhance or prolong the function of helpful proteins that ward off disease. If successful, the approach could lead to new therapies for cancer, immune conditions, rare genetic diseases, and more.
Entact Bio launched this week, backed by $81 million from private investors for the strategy, which it calls targeted protein enhancement. The focus on boosting good proteins, rather than getting rid of bad ones, flips the traditional drug discovery model and opens up a swathe of potential drug targets long overlooked by the biotech industry, including proteins known to suppress tumor growth.
“Most drugs work by blocking the action of a protein that drives disease,” said Sara Buhrlage, a cofounder of Entact and an associate professor at Dana-Farber Cancer Institute and Harvard Medical School. “There’s so much untapped potential in this idea of enhancing the function of a protein that prevents disease.”
Chemists have few tools for bolstering the numbers or activity of helpful proteins. Entact hopes to change that, and it’s at least the third startup to receive a large wad of funding for the idea in the past 18 months.
New York-based Stablix Therapeutics launched in June 2021 with $63 million to develop drugs that stabilize or increase proteins that can stave off cancer, immune system disorders, or rare diseases. And in July of this year, South San Francisco-based Vicinitas Therapeutics launched with $65 million to develop a similar technology with a focus on cancer and genetic disorders.
“My career in drug discovery has always been about inhibiting a protein,” said Victoria Richon, chief executive of Entact Bio. “This is so exciting, because it’s turning everything on its head.”
The startup has worked in stealth mode since it was founded in 2019. In addition to pulling in the largest initial financing yet for a company in the budding field, Entact counts among its cofounders scientists from Dana-Farber and Harvard, the University of Liverpool in England, and the Walter and Eliza Hall Institute of Medical Research in Australia. The company has about a dozen employees, and plans to grow, but Richon wouldn’t reveal its hiring goals.
Entact and its competitors are piggybacking on another hot trend in biotech called targeted protein degradation, in which more than a dozen drug companies are developing small molecule therapies, given as pills, that empower cells to destroy disease-causing proteins. The still-experimental drugs work by grabbing the problematic protein and marking it for destruction in the cell’s trash compactor.
The approach has garnered billions from private and public biotech investors who are excited by the potential to eliminate wily proteins, especially ones that cause cancer. The new approaches for protein enhancement or stabilization, developed by Entact, Stablix, and Vicinitas, remove molecular tags that normally destine a protein for destruction, thus allowing them to stay in the cell longer.
The molecular tags that make all of these tactics possible are called ubiquitin — so named because even before scientists figured out what these molecules did, they had found them ubiquitously throughout the body. Now companies are racing to develop drugs that add ubiquitin to unwanted proteins or remove it from helpful proteins by recruiting natural enzymes specialized to the task. The drugs must be carefully designed to pair the right enzyme with the target protein.
Buhrlage said Entact was founded with an understanding that although the science is still early, a biotech company would be the best way to methodically make the new class of drugs. “It’s going to be a challenge, they understand that,” she said of the firm’s investors. “But the potential reward is so significant, it’s time to invest.”
Richon wouldn’t name specific drug targets or diseases that her company is focused on, and instead emphasized that the protein-enhancing technology “has broad use in multiple therapeutic areas.” But she added that there’s a “straightforward opportunity” to apply the technology to boost helpful proteins to treat cancer, inflammatory diseases, and rare genetic diseases.
Cancer biologists have documented numerous proteins that play an important role in checking out-of-control growth characteristics of cancer. But these tumor suppressors, as they’re known, have largely been overlooked by drug developers who lacked good ways to tap into these cancer-suppressing powers. “We haven’t really had a way to think about [drugging] tumor suppressors,” Richon said. She hopes that will change with Entact’s approach. “This is a very rich area for us to explore.”