One of the most popular targets in drug development, representing about a third of existing drugs, are G-protein coupled receptors — the tiny but integral membrane proteins responsible for recognizing things like light, taste, smell, hormones and pain.
But due to challenges in mapping their structure, the protein family remains largely unexplored.
A slate of companies has emerged over the last few years to change that. If one can figure out the structure of these elusive membrane receptors, it might be possible to create small molecule drugs that overcome the limitations of, say, biologic and peptide therapies. That promise is what gets serial entrepreneur Raymond Stevens out of bed in the morning.
It’s also what recently got his company ShouTi $100 million from a syndicate of blue-chip investors.
ShouTi, a Schrödinger-partnered startup, uncloaked Wednesday morning with a hefty Series B round led by BVF Partners. Stevens launched the company four years ago with Schrödinger co-founder Rich Friesner and landed a $58 million Series A back in 2019. Why wait so long to come out of stealth?
“We asked for the time so that we could stay focused at the beginning,” Stevens told
Endpoints News.
Now the company has 50 staffers and three programs in the works, the first of which is already in the clinic for pulmonary arterial hypertension, or high blood pressure that affects arteries in the lungs and heart. It’s a condition that Stevens and his team believe goes undiagnosed in much of the world.
The second program should be headed for the clinic early next year, Stevens said, while the third is still in early development. The CEO is keeping the targets for those programs under wraps for now.
ShouTi’s roots trace back to Syrrx, a company Stevens founded in 1998 focused on high-throughput structure-based drug discovery. The company was particularly passionate about GPCRs, which scientists knew little about at the time. In 2007, Stevens and his colleagues published the first high-resolution structure of a human GPCR. Shortly after that, he launched Receptos with a platform around the tricky receptors.
“There was a combination of about, you know, 15 different technology developments that all had to come together in order for us to get those very first G-protein coupled receptors,” he said.
Receptos also had an asset that proved quite attractive: an S1P1 agonist now better known as Zeposia, a prescription drug for relapsing forms of multiple sclerosis. The drug was a key point of interest in Celgene’s acquisition of Receptos in 2015, and subsequently Bristol Myers Squibb’s acquisition of Celgene in 2019.
When all was said and done, Stevens was left wanting to build out Receptos’ old GPCR platform. So when Friesner called him with an offer to collaborate in 2017, he jumped.
Some big-name backers have come aboard as well, including Casdin Capital, Cormorant Asset Management, Janus Henderson Investors, Lilly Asia Ventures, Monashee Capital, Sage Partners, Stork Capital, Surveyor Capital, TCG X, Terra Magnum Capital Partners, Woodline Partners, Schrödinger, Eight Roads, F-Prime Capital Partners, Qiming Venture Partners, Sequoia Capital China, TF Capital and Wuxi AppTec.
ShouTi isn’t the only GPCR-focused company getting attention from Big Pharma. Japan’s Sosei Heptares joined forces with both Roche’s
Genentech
and
Takeda
back in 2019 to develop medicines that modulate GPCRs. And it’s estimated that more than 30% of FDA-approved drugs target this class of proteins.
“We’ve really dug in deeply into understanding the function, and we really understand the pharmacology quite well,” Stevens said. “So I think that’s probably one of our biggest advantages is that understanding.”