New targeted therapy approaches win Rain Therapeutics $63M — designed to beat a quick path to approval

Rain Therapeutics is on a tear.

When the biotech got started in the San Francisco Bay Area, it was singularly focused on tarloxotinib, a small molecule inhibitor named for its design to target low oxygen levels in the tumor and thereby sparing healthy tissues. More than two years later, Rain has tripled its pipeline within days, first licensing a research program from Drexel University, then more recently nabbing a Phase II-ready drug from Daiichi Sankyo.

It also has $63 million in fresh funding to push all three programs, with Boxer Capital, Cormorant Asset Management, Samsara BioCapital, Janus Henderson Investors and Logos Capital now in its corner alongside existing investors BVF Partners and Perceptive Advisors.

Through it all, Rain is retaining its targeted focus, noted CEO Avanish Vellanki.

Starting out with tarloxotinib, for instance, allowed them to tap into the Exon 20 niche within the broader EGFR-positive non-small cell lung cancer as well as NRG1, EGFR, HER2, and HER4 fusions.

Meanwhile RAIN-32, the therapy from Daiichi Sankyo that has superseded tarloxotinib as Rain’s lead program, targets MDM2 (which inhibits p53, blocking its tumor suppressing effect). The other preclinical program focuses on RAD52, which CSO Robert Doebele calls a critical backup pathway for cancer cells that already have other defects in the DNA damage response pathway.

A veteran trial investigator well-versed in oncogene targets who’s continued to practice and research at the University of Colorado after co-founding Rain, Doebele said new approaches are needed to open up new waves of cancer treatment to follow up on the seven oncogenes now covered by FDA-approved treatments.

“The number of targets that we can directly inhibit like that — like ALK, EGFR, ROS — are somewhat thinning a bit,” he said. “But I think these new strategies where we’re targeting the p53 pathway and reactivating or using synthetic lethality strategies in a very similar way, basically taking advantage of cancer-specific vulnerabilities, is absolutely of interest.”

A general uptick in next-generation sequencing is also speeding up the identification of patients, as Rain has witnessed firsthand with the ongoing Phase II for tarloxotinib.

As with entrectinib and larotrectinib for patients with NTRK fusions, both of which Doebele has helped develop, Rain believes RAIN-32 lends itself to tumor-agnostic — or biology-driven as he prefers to call it — development.

“That’s still a very very young field,” he said.

The Series B gives Rain about 2.5 years of runway, fueling its lean team of 8 all the way to the completion of a pivotal trial for RAIN-32 in liposarcoma. Within the subpopulation the company is focusing on, Vellanki said, nearly 100% has an MDM2 gene amplification.

While other companies like Roche and Ascentage have developed MDM2 inhibitors, toxicities remain a big problem for the field, according to Vellanki. Daiichi scientists tried to solve for that with a different dosing schedule that gives patients time to recover from the side effects.

“Broadly speaking whenever you have version 2.0 or version 3.0 of any technology, you’re able to compensate for the problems of the version 1.0,” he said. “Advancements of technology always allow you to fine-tune technologies to solve the problems that you didn’t know were there in the first place with the initial set of targeted therapies.”

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