Touting CD161 as a test case for single-cell tech, Longwood-backed Immunitas bags $58M for next-gen I/O work
Back when Longwood unveiled its latest immunotherapy startup, Immunitas, the VC’s co-founder Lea Hachigian talked at length about how its single-cell genomics analysis platform could enable researchers to “ask questions of the immune system we weren’t able to ask before,” understand human biology on a much deeper level and identify targets that nobody else was working on. They just couldn’t disclose the precise target for the lead program.
This February, Immunitas finally did — publishing a paper in Cell that zeroes in on CD161 as a receptor on T and NK cells that suppresses their ability to kill glioma cells.
Months later, the startup is back with $58 million in fresh cash to steer a CD161-blocking antibody toward the clinic while fueling a slate of other programs behind it. The goal, Immunitas CEO Jeffrey Goldberg told Endpoints News, is to keep expanding the pipeline at a rate of about one program per year.
Kai Wucherpfennig, chair of Dana-Farber Cancer Institute’s department of cancer immunology and virology, co-founded Immunitas with Aviv Regev (before Roche’s Genentech recruited her to run R&D), Dane Wittrup of MIT and Mass General’s Mario Suvà.
For Wucherpfennig, the discovery of CD161 was a testament to the key advantages of the single-cell platform he helped invent, which started out analyzing hundreds of cells but can now work with hundreds of thousands at a time, at high resolution. Through isolating T cells from patients’ tumor samples (separate from, say, stromal cells, tumor cells, and so on), clustering them by gene expression and then examining different populations, his team essentially came up with an atlas of immune cells in glioma — all based on human samples.
“We’ve been asked multiple times, why do other people not pick it up? And the reason actually is that the biology is very different between mice and humans,” he said. “Most people start with mouse models, and then in mice there are actually multiple genes that encode CD161 like molecules. Some of them are inhibitory, some just are activating receptors, and the biology is very confusing. And in humans it’s actually more straightforward. There’s a single gene that encodes an inhibitory receptor, OK. And so most people have looked at this — I know some people have looked at this and said, never mind. And they never really looked at the human biology.”
As Immunitas — now grown to 20-plus staffers — carried on the work, once again relying on the single-cell sequencing and analytics tech, they found out that the receptor is not just associated with glioma. CD161 appears to be in play in T and NK cell interactions with multiple cancer types spanning solid and liquid tumors, giving the biotech multiple options to explore in the first human trials, with an IND slated for the first half of next year.
Specifically, Immunitas’ IMT-009 is designed to bind to CD161 on T and NK cells and prevent it from interacting with CLEC2D on tumor cells, thereby restoring the immune cells’ cancer-killing power.
Wucherpfennig and Goldberg figure there are many more immuno-oncology targets out there similarly lurking in corners traditional discovery methods can’t uncover.
The promise has drawn a sizable syndicate. Agent Capital led the round, which featured Medical Excellence Capital, 120 Capital, Solasta Ventures, Mirae Asset, Ono Venture Investment, The Mark Foundation for Cancer Research, NS Investment, BrightEdge (American Cancer Society) and the Leukemia & Lymphoma Society Therapy Acceleration Program. Existing backers also returned: They are Alexandria Venture Investments, Evotec, Leaps by Bayer, M Ventures, Novartis Venture Fund and, of course, founding investor Longwood.
Beyond that, the scientist also sees the upcoming work as part of a bigger experiment to test the underlying platform as a comprehensive tool to close the loop on translation.
“We’re also thinking about how we can use single cell technologies to actually understand what the drug does in patients — you know, once we start a clinical trial,” he said. “There obviously are some logistical challenges with sample procurement, et cetera, but it could actually be an exciting opportunity. So we — we use single cell technologies to discover it, we use single cell technologies to define indications, and then also study mechanism of action in people.”