The biotech doing the opposite of protein degradation - stabilizing the proteins your body throws away too soon.
STABLIX, INC. — New York, NY / Boston, MA
Targeted deubiquitination therapeutics, in one wordmark.
For the better part of a decade, the most talked-about idea in drug discovery has been demolition. A wave of companies learned to hijack the cell's disposal system - the ubiquitin-proteasome pathway - to tag disease-causing proteins and haul them to the shredder. Stablix, Inc., a preclinical biopharmaceutical company founded in 2021 and co-located in New York City and Boston, was built on the mirror image of that idea.
Instead of marking proteins for destruction, Stablix removes the destruction tag. Its molecules recruit enzymes called deubiquitinases (DUBs) to a chosen target protein and strip away the ubiquitin that would otherwise send it to be broken down. The result: proteins that were being cleared too quickly are restored to healthy, therapeutic levels. The company calls the field it is trying to create targeted protein stabilization, or targeted deubiquitination therapeutics.
"Stablix is pioneering an entirely new field of targeted deubiquitination therapeutics to bring transformative medicines to patients with unmet medical need."
It is a simple reframing with wide consequences. Many diseases are not caused by a protein that is present and harmful, but by a beneficial protein that is missing or too scarce. If you can keep that protein around longer, you have a therapy. That is the wager Stablix has raised roughly $78 million to test.
The platform is called RESTORE. The molecules it produces are heterobifunctional - meaning each has two business ends. One end grabs the target protein; the other end grabs a deubiquitinase. By holding the two together, the molecule brings the DUB's ubiquitin-editing activity to bear on exactly the protein you care about.
The crowded, well-funded lane. Molecules (like PROTACs) recruit ubiquitin ligases to add ubiquitin, sending a harmful protein to the proteasome for destruction.
Stablix's lane. RESTORACs recruit deubiquitinases to remove ubiquitin, rescuing a beneficial protein from destruction and boosting its levels and activity.
The distinction matters commercially as well as scientifically. Category creators tend to set the terms of the deals that follow - and in April 2023, that thesis got its first big external validation.
As a preclinical company, Stablix does not yet sell a drug. Its near-term customers are large pharmaceutical partners who license molecules from the platform - and its ultimate beneficiaries are patients. The company is initially pointing targeted protein stabilization at three areas: cancer, rare diseases and immunological disorders.
Rare diseases are a natural fit. Many are caused by proteins that are made but destabilized. A RESTORAC that keeps such a protein around could, in principle, address conditions that have resisted conventional drugging. Cancer and immunology open up when the goal is to restore a tumor-suppressing or immune-regulating protein the body is losing.
The problem Stablix is really solving is a gap in the medicinal toolkit. For years, chemists could inhibit a protein's activity or, more recently, degrade it. Increasing a specific protein's level with a small molecule was far harder. Deubiquitinases were considered messy and difficult to drug, which is precisely why the space was open.
Stablix's answer was to build the chemistry to make that recruitment precise - turning an underused class of enzymes into the engine of an entire platform.
Designs heterobifunctional small molecules that selectively recruit active deubiquitinases to a target protein, precisely removing ubiquitin to raise the target's levels and activity.
The bifunctional small molecules produced by the platform - each bridges a chosen target and a DUB, editing ubiquitin to restore deficient proteins to therapeutic levels.
Discovery-stage work applying stabilization to cancer, rare diseases and immunology. Specific development candidates are not yet publicly disclosed.
Stablix runs the classic platform-biotech playbook: fund early discovery with venture capital, then monetize the platform two ways at once - proprietary programs advancing toward the clinic, and partnerships that bring in non-dilutive cash.
The template arrived with Vertex Pharmaceuticals. Under the April 2023 strategic collaboration and license agreement, Stablix applies its platform to discover RESTORAC candidates against specified targets; Vertex gets an exclusive license to certain molecules and takes responsibility for development and commercialization. Stablix received an upfront payment including a convertible note investment, and is eligible for research, development, regulatory and commercial milestones plus tiered royalties. Exact figures were not disclosed.
"Stablix will apply its proprietary platform toward the discovery of novel heterobifunctional small molecule drug candidates against specified targets involved in multiple diseases."
The platform originated in the laboratory of Henry Colecraft at Columbia University, where he and Scott Kanner developed a way to selectively recruit deubiquitinases to proteins of interest. Leadership pairs that founding science with seasoned biopharma operators.
Tony Kingsley - the contact of record for this profile and Stablix's former chief executive - brings a track record that includes leading TARIS Bio through its 2019 acquisition by Janssen and serving as president and CEO of Scholar Rock. It is the kind of operator's resume that signals a platform aiming squarely at partnerships and clinical translation.
Debuts with a $63M Series A led by Versant Ventures, with NEA, Cormorant, Euclidean Capital and Alexandria.
A further ~$15M tranche in November 2022 extends the runway toward ~$78M total raised.
Signs a strategic collaboration and license agreement with Vertex Pharmaceuticals for RESTORAC molecules.
Tony Kingsley named CEO, succeeding interim CEO Carlo Rizzuto of Versant Ventures.
Stablix sits inside the broader "induced proximity" and protein-homeostasis space, alongside the well-capitalized degradation players - Arvinas, Kymera, Nurix, C4 Therapeutics and Monte Rosa among them. But where those companies compete to eliminate proteins, Stablix occupies the largely uncontested stabilization side of the same biology.
That positioning is the whole point. A 16-person company does not out-spend the field; it finds the door no one else walked through. Backing from Versant, NEA, Cormorant, Euclidean and Alexandria, plus a Vertex partnership within two years of launch, suggests the door was worth opening.
Where a PROTAC tags a protein for destruction, a RESTORAC removes the tag - the same machinery, aimed the other direction.
Deubiquitinases were long seen as too messy to drug. Stablix built its entire platform around them.
The science came out of a Columbia University physiology and cellular biophysics lab.
Operations are split between New York City and Boston, straddling two major life-science hubs.
Stablix is a preclinical biopharmaceutical company developing targeted protein stabilization - small molecules that recruit deubiquitinase enzymes to remove ubiquitin from target proteins, restoring them to therapeutic levels or correcting their function.
Protein degraders (like PROTACs) tag proteins for destruction. Stablix's RESTORACs do the reverse - they remove the ubiquitin tag to stabilize and boost beneficial proteins instead of eliminating harmful ones.
It is Stablix's discovery engine that designs heterobifunctional small molecules (RESTORACs) to bridge a target protein and a deubiquitinase, editing ubiquitin to increase the target's levels and activity.
Roughly $78M, including a $63M Series A led by Versant Ventures with NEA, Cormorant, Euclidean Capital and Alexandria - plus a partnership with Vertex Pharmaceuticals.
Its preclinical programs focus on cancer, rare diseases and immunological disorders, where restoring deficient or dysfunctional proteins could offer a new therapeutic approach.
Profile compiled from public sources. Figures are approximate where noted. No video interviews or product demos were publicly available at time of writing.