Startups, Venture

Protein degradation 2.0? Third Rock sinks $56M into Cedilla’s unusual approach

Third Rock Ventures is trotting out the latest player in the hot space of protein degradation, infusing the new startup with $56 million in launch money to find out if its unconventional approach to junking proteins works better than its rivals.

The upstart goes by Cedilla Therapeutics, and it’s entering a field of drug development that’s picking up a lot of steam this year. The concept behind the emerging space is simple enough: where protein inhibition has led to some advanced medicines, degrading proteins could prove a more fruitful solution. The approach could have major benefits over traditional small-molecule strategies, including the potential to cut down systemic drug exposure and the ability to tackle target proteins once considered undruggable.

Many players in protein degradation are tackling the field by hijacking the ubiquitin process, essentially tagging disease-causing proteins for destruction by recruiting an E3 ligase to the target, which sends the protein to the cell’s natural “garbage disposal.” It’s a smart idea, but it’s also quite complex to build these molecules. Early pioneers in the protein degradation space are taking this approach now, including Arvinas, Kymera, and C4 Therapeutics, among others.

Cedilla is taking aim at a different avenue, the company’s CEO Alexandra (Sandra) Glucksmann tells me.

“What we’re trying to do is upstream of that whole process,” she said. “Instead of starting with a technology and then having to find a target — and being limited by the tech we have — we are instead starting with a target of interest and applying different methodologies to degrade it.”

Brian Jones

Third Rock has been gunning away on this idea for months now, recruiting Glucksmann, a founding employee and the ex-COO of Editas, to serve as entrepreneur-in-residence at the venture firm six months ago (with plans to put her at the helm of Cedilla straight away). Glucksmann said the company already employs 12 people.

In short, Cedilla is using more traditional small molecule drugs to destabilize disease-causing proteins ahead of the ubiquitination process. Once the proteins are unstable, the cell recognizes them as dysfunctional and tosses them in the garbage disposal.

One way the company is going about this is by mapping out the chemical bonds between proteins. The goal, Glucksmann says, is to “orphan” a target protein by disrupting its bonds with other proteins, tipping the target into an unstable state.

Cedilla is already running 8 early-stage programs in parallel, Glucksmann said, using the new funds from Third Rock to ID which candidates they’ll take to the clinic. The company thinks this tech could be have widespread applications.

“We are initially focused on oncology targets,” said Cedilla’s CSO Brian Jones. “We also believe our small molecule approach is broadly applicable, for example to access targets in the central nervous system.”


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