Monte Rosa pulls in $95M to test its 'molecular glues,' and the first target is GSPT1
Protein degradation has been a fundraising hotbed in recent years, with investors drooling over the potential to drug the “undruggable.” Already an investor darling, Monte Rosa Therapeutics and its “molecular glues” are going back to the well with the clinic on the horizon — and the biotech’s finally revealing its first target.
Monte Rosa hauled in a $95 million Series C to pave the way for its lead protein degrader program to make a run to the clinic and flesh out its pipeline, the biotech said Friday. The round was led by Avoro Capital Advisors.
Unlike other small molecule degraders such as PROTAC that function much like inhibitors, Monte Rosa’s degraders help bind E3 ligases — an enzyme laden with ubiquitin, a key regulatory protein in the degradation process — with targeted disease-causing proteins. The resulting “glue” avoids the need for available binding sites, which are impossible to hit on the so-called “undruggable” proteins.
Monte Rosa’s lead program, which the biotech hopes to take into IND enabling studies by the middle of the year, will target GSPT1, a regulatory protein implicated in the synthetic lethality of solid tumor cells, CEO Markus Warmuth told Endpoints News. It’s the first time the company is showing its hand in terms of an initial target after staying mum through two prior funding rounds.
The biotech plans to use the proceeds to scale its drug discovery platform for novel targets as well as build its trans-Atlantic team in Boston and Basel, Switzerland, Warmuth said. Since the biotech last closed its $96 million Series B in September, Monte Rosa has worked out the kinks in its discovery platform and is ready to keep building.
“The big breakthroughs over the last six months have really been on platform,” he said. “We now have good validation that our computational approach … has worked out, and we’re looking to really scale the platform aggressively now.”
Protein degradation has turned into a hotbed of investment in recent years, but “molecular glues” themselves aren’t brand new. Leprosy therapy thalidomide, first approved way back in 1998, functions the same way but found its mechanism of action largely by accident. Meanwhile, other protein degraders such as PROTAC look to accomplish the same thing by acting as a functional linker between the protein receptor and ubiquitin enzyme.
That structure makes PROTAC larger than molecular glues, which can limit its drug-like properties and lower its optimization for specific targets, Warmuth said.
With its discovery platform growing, Warmuth remained mum on where his team was looking for its next targets, but did point specifically to transcription factor proteins that bind to DNA to turn certain genes “on” or “off.” Those proteins are an obvious target due to the vast majority of them being unddruggable.
“In our pool of targets we have discovered, there’s a clear enrichment for transcription factors,” Warmuth said. “We’re not limited to transcription factors, but that’s a family that is particularly attractive.”
Monte Rosa will have a hard time differentiating itself in a molecular glue field packed with competitors. In December, Neomorph, a Dana-Farber-backed play at the field, snared a $105 million Series A. Earlier in the month, AbbVie placed a $55 million upfront bet on Frontier Medicines to develop drug candidates targeting E3 ligases. Frontier will also be scouting small molecule binders to target, AbbVie said.
Other drugmakers, including Sanofi, Roche, Bayer, Gilead and Vertex, have all inked their own protein degradation pacts in the recent past.
