Revolution Medicines started out in 2014, with a platform that breaks down natural compounds into their composite parts and reassembles them into usable drugs. The company has since zeroed in on oncology and now, with a $56 million round in the bag, is pushing its lead program into the clinic.
The Bay Area biotech is focusing on what it calls "frontier targets," or targets that have "compelling biology" regarding their role in driving a cancer or bypassing an antitumor immune response, but that have been undruggable, or not adequately druggable, in the past, said Revolution CEO Mark Goldsmith, M.D., Ph.D. Its lead program is a molecule that blocks SHP2, a protein that regulates cellular proteins, but also acts as a driver of certain cancers and as a signaling node in various regulatory pathways. These pathways include the RAS pathway, which is dysregulated in a number of cancers.
The new capital, raised from a syndicate that includes Nextech Invest, The Column Group and Third Rock, will carry the SHP2 program into the clinic. The company is preparing an IND for the candidate and aims to start testing it in patients with advanced cancers later this year. While the IND is a "big focus of resources and attention," Revolution will continue with its discovery research linking the target to specific pathways and cancer genetics. For example, Goldsmith said, the company learned that SHP2 and its regulation of the RAS pathway are a good target for tumor cells with very specific RAS mutations.
Revolution expects to test its SHP2 drug as a monotherapy and in combination with other treatments, Goldsmith said. These could include targeted therapies in which the inhibition of SHP2 may delay or overcome the development of resistance to treatment.
“We appreciate the strong support shown by our founding and new investors in this significant financing that will fuel the advancement of our exciting SHP2 program and innovative pipeline,” Goldsmith said. “The raise of new capital, expansion of our executive team and board with seasoned leaders, and multiple presentations about progress in our SHP2 program at the recent AACR conference all reflect enormous momentum in our effort to outsmart cancer.”
Revolution can attack targets that were previously considered undruggable because it has skills and technology that others in the industry don't, according to Goldsmith. For example, a target may have "atypical features" that "require very elaborate chemistry." The company may identify a target based on how it functions, or the role it plays in a biological pathway.
San Diego-based Vividion Therapeutics is also aiming to expand the number of therapeutic targets. The biotech launched in February 2017, with synthetic and proteomic chemistry platforms designed to identify previously unknown druggable targets in the human proteome: the entire set of proteins that can be expressed by the human genome.
“We as an industry have struggled with inefficiency and safety issues appearing late in programs and the horrible failure to target proteins that are highly validated, but not druggable,” said Executive Chairman Tom Daniel in a previous interview with FierceBiotech.