Stablix Therapeutics

Stablix comes from the lab of co-founder Henry Colecraft, Ph.D., at Columbia University in New York. (Stablix Therapeutics)

Stablix Therapeutics

After a decade of R&D into the process of protein degradation, Stablix is attempting to take its findings and apply them to a “completely new white space” in protein stabilization.

CEO: Carlo Rizzuto, Ph.D.

Founded: April 2021

Based: New York City

Clinical focus: Stablix is working on building up a chemical library of small molecules that can recruit different deubiquitinase enzymes and developing in-vivo proof of concepts with molecules that come out of its platform over the next 18 months.

The scoop: Protein degradation has dominated biopharma for years, but there is plenty of fertile ground left for exploration.  Stablix is attempting to apply the learnings of its protein degradation research to stabilizing and restoring protein expression, an approach that the biotech thinks can be applied to anything from rare diseases to oncology to autoimmune disorders.

What makes Stablix fierce: From the outside, diseases can look quite different. On the inside, there’s a similar biological mechanism powering a lot of diseases, and Stablix thinks it has the ability to go after it.

“The idea is, if we could find a general method to rescue that protein expression, we could have a general approach for treating many diseases,” said Henry Colecraft, Ph.D., co-founder and chair of Stablix’s scientific advisory board. Stablix comes out of Colecraft’s lab at Columbia University in New York where he is a professor of physiology and cellular biophysics.

The protein degradation field has been burgeoning for years now, and the pharmaceutical industry saw it as a way of treating what is “traditionally thought of as undruggable,” Colecraft said. The ability to knock down different proteins has broad applications and can work across a plethora of end targets.

“So, in retrospect, I think most people would think that developing the opposite of it is sort of easy, but with everything else, it becomes obvious in hindsight. I think once we did it and showed the proof of concept of it, the beauty is its simplicity. Everybody will say, ‘Oh, why didn’t I think of that, and that’s how these things usually turn out,’” Colecraft said.

The early days won’t be easy for the biotech, still in its first year of operation, but Stablix at least has a “proof of principle” from the degradation field, said Carlo Rizzuto, Ph.D., acting CEO of Stablix and a partner at Versant. Rizzuto has been a partner at Versant since 2012 and served as a director or interim CEO across about a dozen biotechs incubated out of the venture group.

“We’ve never had a really good way to stabilize proteins and increase their levels, and that’s what Henry and his team have developed here,” the CEO said.

On the opposite side of the tracks, biopharmas have been degrading targets “with molecules that do a lot of what we want to do, though they recruit different types of enzymes,” Rizzuto said. Whereas degraders target enzymes such as E3 ligase, Stablix will recruit the deubiquitinase enzymes, or DUBs, which remove ubiquitin from a target and then stabilize it.

Aside from its innovation in the degradation arena, Stablix has a blueprint for viruses. Herpes and poxviruses, and “all of the large name” ones have been “manipulating the system in both directions,” Rizzuto said. They recruit DUBs; they recruit and encode E3 ligases to degrade or stabilize different targets.

“So, what we’re trying to do is capitalize on these genius viruses that have been showing how to do this but then using all the chemical tools that have been developed since then.”

For now, the startup is working on translating the work from Colecraft’s lab into a library of small molecules that recruit a variety of DUBs to go after different targets. With variations of sub-cellular localization, there are nuclear DUBs, cytoplasmic DUBs and others. “It’s useful to have a bit of a toolkit in terms of what we recruit,” Rizzuto said.

Stablix, with 10 employees, is a heavily science-based team at the moment, so building out the chemical library and creating an in-vivo proof of concept with molecules that emerge from the platform are key milestones in the coming 18 months, Rizzuto said. Also on the small team is Kevin Sprott, Ph.D., who is senior vice president of drug discovery. He previously held the same role at SMOC Therapeutics and has been an independent consultant.

Beyond that timeframe, Stablix aims to get at least one program into the clinic with its initial $63 million investment.

With the clinic still far away, Stablix hasn’t disclosed the exact indication it’s targeting first, but rare diseases, oncology and autoimmune disorders are all possibilities, Rizzuto said.

Cystic fibrosis, for example, experiences excessive ubiquitination, which tags proteins for destruction by the cells’ garbage disposal-like proteasomes. For diseases like that, the “biology is extremely well understood,” which also makes it an appealing target.

In oncology, tumor suppressors can often be a target of cell degradation, which allows the tumor to proliferate. Stabilizing the protein would be of benefit. And in autoimmune diseases, “viruses are masters of manipulating the immune system so that they can survive, so that validates a whole number of targets in the autoimmune space for us,” Rizzuto said.

Investors: Versant Ventures, New Enterprise Associates, Cormorant Asset Management, Euclidean Capital and Alexandria Real Estate Equities.

Stablix Therapeutics