Going after an old GSK target in a new way, a Yale spinout hits the clinic and nabs a modest raise
About a year and a half ago, a Yale professor took a shot at engineering a cancer therapy that had once flummoxed researchers at GlaxoSmithKline. The company announced its next steps Thursday, earning a modest fundraise and entering the clinic.
Simcha Therapeutics closed a $40 million Series B and has begun dosing patients in a Phase I/II trial for its lead program, the biotech announced. The raise should take Simcha into 2024 and help complete the just-launched Phase I portion, a Phase II monotherapy study and a Phase Ib combination trial with a checkpoint inhibitor, founder Aaron Ring told Endpoints News.
Ring’s theory revolves around stimulating the IL-18 pathway, trying to increase the body’s immune response to tumor microenvironments using what Simcha calls a “designer cytokine.” It’s essentially the re-engineering of an old GSK effort that began in 2004 and scuttled early, as patients’ tumors progressed regardless of how much IL-18 was agonized.
But by targeting a group of receptors that the microenvironments had all but shut down, Ring found he could create a decoy to evade the cancer’s jamming system and get the proper cytokines where they needed to go. He outlined the initial results in a Nature paper from June 2020, which proved foundational to Simcha’s efforts.
It’s part of a broader effort by immunotherapy researchers to find the next big cancer drug, following the success of other medicines like anti-PD-1 antibodies — though Ring noted Simcha is taking the opposite approach in an IL-18 agonist.
“Our conviction shared by many is that we can’t accept a nature solution. When it comes to cytokines, we need to engineer them for a deliberate therapeutic purpose,” Ring said. “What’s limited many cytokines to date is just the fact that they’re too broadly active, too broad and a nonspecific set of immune cells.”
Simcha’s molecule, known as ST-067, is the first IL-18 pathway agonist being studied in humans since GSK’s last study was shuttered nearly 10 years ago, Ring added. Those efforts went through a Phase II melanoma study, and though it was well tolerated for a cytokine, it induced only one partial response out of 63 patients.
When Ring first came across these results, he found them “really shocking,” because it appeared to be the right signal hitting the right cells. It led him to the microenvironment biology Simcha is now trying to agonize, bringing a “laser focus” on trying to replicate his initial preclinical tests back in 2017.
The biotech is starting on a broad slate of solid tumors for its initial testing, utilizing the Phase I portion as a dose-escalation study. Simcha’s plan is to recruit any patient that’s progressed on existing checkpoint immunotherapies, not focusing on specific cancer types or genetic mutation subsets.
It’s too early to say when Simcha might have the data it needs to move on to Phase II, but Ring said he’s aiming for the typical timelines for what similar agents in the class have achieved. The plan is to test the compound broadly, looking at monotherapy regimens as well as in combination with other approved therapies.
But Ring hopes his approach will set Simcha apart from other immunotherapy companies.
“What differentiates us from the other pathways is that there are now dozens of companies pursuing cytokine therapies in the IL-2, IL-15 space,” Ring said. “But this is a completely different pathway…Never before in patients has anyone been able to decouple the effects of IL-18 signaling from the binding protein.”
Thursday’s round was led by SR One Capital Management and joined by other new investors, including BVF Partners, Samsara BioCapital, Rock Springs Capital, ArrowMark Partners and Logos Capital.