Pharma, Startups

Startup targeting protein degradation in cancer raises $37M

Cleave Biosciences is trying to prevent protein degradation, a hallmark of certain cancers, in its aim to develop drugs that work on solid tumors and blood cancers.

dollars, wealth

Cleave Biosciences wants to cut protein pathway addiction to help kill off cancer cells in both solid tumors and blood cancers, and it just got $37 million to progress its agenda.

The Burlingame, California, company announced Monday that it had raised that amount in a Series B funding round that attracted new investors like Celgene, Nextech Invest and Arcus Ventures. Previous investors like  5AM Ventures, Clarus Ventures, New Enterprise Associates (NEA), Orbimed Advisors, U.S. Venture Partners, Astellas Venture Management and Osage University Partners also chipped in.

To date the company has raised $91 million, that includes $54 million in a Series A round of financing that closed in 2013, said Laura Shawver, the founding CEO of Cleave Biosciences in a phone interview.

The money will fund two Phase 1 clinical trials of its lead candidate — CB 5083 that inhibits the p97 enzyme that controls different aspects of protein homeostasis. One trial is aimed at testing the drug candidate in solid tumors, while the second one is targeting blood cancers. The initial target is multiple myeloma.

“Protein degradation has been shown to be important in certain tumor types and of course multiple myeloma is the poster child for that,” Shawver explained. “They become addicted to a pathway and in this case the pathway is protein degradation and by shutting that pathway down, the tumor cells get killed.”

In fact the name of the company is inspired by what it wants to achieve – to cleave or cut away.

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“In protein degradation, there’s ubitquitin that gets added to a protein which acts as a zip code for taking it to proteasome for degradation,” Shawver explained. “That gets added on and it has to be cleaved off and that is an example of one moiety or one part that gets added on that then has to be clipped back off.”

CB 5083 is targeting this pathway and aims to shut it down “longer and harder” and achieve efficacy in solid tumors whereas drugs like VELCADE (bortezomib) and Kyprolis (carfilzomib) targeting multiple myeloma work well on blood cancers, but do not work on solid tumors, Shawver said.

Increasingly, advancement in science is redefining how cancer should be treated, whereas in the past drugs would be developed for whole classes of patient populations — say lung cancer or colon cancer or breast cancer.

“Now we know that focusing on subsets that have a greater chance to respond is the better to way to approach drug development,” Shawver said.

Hence Cleave Biosciences is focused on the p97 enzyme and protein degradation. That piqued the interest of Nextech Invest, whose CEO is joining Cleave Bioscience’s board after investing in the startup.

“We particularly respect the team’s deep understanding of the targets that are central players in a number of cancers and we’re pleased to support their efforts to develop novel small molecules as potential first-in-class therapies,” said Alfred Scheidegger, in a statement.

A study published in the Proceedings of the National Academy of Sciences, October 2010,  concluded that there is a rationale for targeting the p97 enzyme in cancer therapy. Shawver contends that Cleave Biosciences’s CB 5083 is the first p97 inhibitor in clinical development.

“From a standpoint of p97 itself, I am sure there are others that are working on this target and may be  even a target class, but we’re first into the clinical development with such a compound,” Shawver said.

The goal of these Phase II clinical trials, where roughly 100 patients are expected to be enrolled, will be to arrive at the safest maximum dose of Cleave’s CB 5083 drug.

Photo: freedigitalphotos user Salvatore Vuono