Cedilla Therapeutics launches with $56M to target protein degradation in cancer

Cedilla Therapeutics launched Tuesday with a $56 million investment from Third Rock and a mission to develop small molecules that target the stability of cancer-driving proteins. Others have worked on degrading protein targets in the past, but they have not used small molecules to do it. 

Other companies are working with what Chief Scientific Officer Brian Jones calls the downstream effector machinery. One approach blocks enzymes involved in ubiquitination, a process whereby a damaged or unneeded protein is tagged with the protein ubiquitin and then sent to a protein complex called a proteasome, where it is degraded. 

But proteins aren't just a priori degraded, Jones said. Rather, the cell makes changes to protein stability upstream of ubiquitination. Cedilla is targeting these processes. 

"Where we are looking is in pivotal events upstream of this machinery that govern the transition [of proteins] between an operational state to a susceptible state." It is this transition that makes proteins visible to the downstream machinery for degradation. 

“We have designed a systematic approach to discover the rules that govern protein stability, which we will apply to find new points of therapeutic intervention. Our integrated product engine allows us to prosecute any protein of interest and to deliver precisely targeted therapeutics to patients in need," said CEO Alexandra Glucksmann, Ph.D., formerly the chief operating officer at Editas, in a statement. 

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The Cambridge, Massachusetts-based biotech is taking a multipronged approach, which includes three target-centric methodologies. The first is having small molecules bind to target proteins, triggering a biophysical change that makes them recognizable by the degradation machinery, Jones said. The second involves upstream regulators—instead of targeting the protein itself, the small molecule targets a process that governs the stability of the protein. And the third is called "protein orphaning," which disrupts the stability a protein gains when it is complexed with other proteins by disrupting protein-protein interactions. 

The fourth approach is unbiased: implementing large-scale proteomics to map protein susceptibility. This allows the company to assess every protein in the proteome to find out what conditions might favor—or hinder—degradation, and identify which of its three methodologies is best for each case, Jones said. 

Cedilla's initial focus is cancer, but it thinks its approach could be broadly applicable in a range of diseases, including central nervous system disorders and rare disease. For the moment, the company is starting discovery programs around some targets of interest and is "firing up the product engine."