Many drugs work by binding to a protein and blocking it. Technology for eliminating disease-causing proteins altogether remains experimental, but this approach has gained ground in the past year with hundreds of millions of dollars raised and compounds advanced into clinical testing. Monte Rosa is one of the newer companies in this “protein degradation” space and it has secured $96 million in financing as it looks to bring its first compound into human testing next year.
The Series B round of funding announced Thursday was led by Aisling Capital.
Targeted protein degradation involves using a cell’s built-in system for recycling old or damaged proteins as a means of getting rid of the ones that cause disease. The trick is ensuring that these problem proteins are recognized by the proteasome, a cell’s protein recycling machinery.
In order for protein degradation to work, the target protein needs to have a binding site for the molecular tag that marks it for disposal. Not all proteins have these sites. Monte Rosa aims to overcome that shortcoming by reshaping the target protein with small molecules that Markus Warmuth, CEO of the Boston-based company, describes as “molecular glue.” This glue binds to the target protein, reshaping it in such a way that another protein—one that marks a problem protein for disposal—can bind to it.
“It’s quite a different way of causing a rendezvous of two different proteins,” he says.
Other companies developing protein degrading drugs include Arvinas (NASDAQ: [[ticker:ARVN]]) of New Haven, CT, and Cambridge, MA-based Kymera Therapeutics (NASDAQ: [[ticker:KYMR]]). The drug candidates from those companies require a ligand, a molecule that binds to a receptor. Warmuth says a molecular glue-based drug doesn’t require a ligand, which means that the technology has the potential to reach more disease targets, including proteins previously deemed “undruggable.”
This glue-based approach is already employed by at least one drug, though the specific mechanism wasn’t known at first. Lenalidomide (Revlimid), a cancer therapy developed by Celgene and now marketed by Bristol Myers Squibb (NYSE: [[ticker:BMY]]), interacts with a target protein in a way that marks it for degradation by the proteasome, Warmuth says. Monte Rosa is taking the mechanism employed by lenalidomide further with its technology, which designs small molecules that serve as molecular glues. Monte Rosa’s initial focus is cancer, though Warmuth says the company’s technology can address a wide range of diseases.
Monte Rosa emerged from stealth in May announcing a $32.5 million Series A financing. The company was founded in 2018, backed by about $20 million from Versant Ventures, Warmuth says. The venture capital firm housed the startup in Ridgeline, its Basel, Switzerland-based biotech incubator. The May announcement extended the Series A financing by $12.5 million from new investor New Enterprise Associates, Warmuth says.
Since emerging from stealth, Warmuth says that Monte Rosa has made progress in understanding the targets it can address, as well as ways to make proteins more likely to be amenable to its approach. The company is now moving toward selecting a lead candidate, which will be advanced to the preclinical research needed for a regulatory submission to begin a clinical trial. Warmuth hopes to begin that study by the end of 2021.
Several protein degrader biotech companies have inked deals to develop drugs in partnership with big pharmaceutical companies. Nurix Therapeutics (NASDAQ: [[ticker:NURX]]) is partnered with Gilead Sciences (NASDAQ: [[ticker:GILD]]) and Sanofi (NYSE: [[ticker:SNY]]). In July, Sanofi entered a separate partnership with Kymera, which already had an alliance with Vertex Pharmaceuticals (NASDAQ: [[ticker:VRTX]]). Arvinas is working with Bayer, Roche, and Pfizer (NYSE: [[ticker:PFE]]).
Monte Rosa does not currently have any such alliances, though Warmuth says there’s been “a lot of interest from big pharma companies in our platform and our approach.” Though Warmuth adds that he’s open to a partnership with a larger company, the near-term plan is for Monte Rosa to develop its programs on its own and the new financing enables the biotech to do so independently. Monte Rosa will use the new money to develop four programs, advancing two of them to clinical testing. The other two will be advanced to lead optimization. The company also plans to further develop its technology platform and expand it beyond oncology.
The new financing included participation by founding investor Versant and returning investor New Enterprise Associates. The round also added new investors HBM Healthcare Investments, Cormorant Asset Management, GV, Amzak Health, Casdin Capital, Sixty Degree Capital, and Cambridge Asset Management.
Image: iStock/Michael Burrell
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