Septerna launches for new approach to targeting GPCRs

Septerna, a biotech company cofounded by chemistry Nobel laureate Robert Lefkowitz, is launching today with a $100 million funding round.

Lefkowitz shared the Nobel Prize in Chemistry in 2012 for deciphering G protein-coupled receptors, or GPCRs, signaling proteins that allow cells to communicate with each other and respond to outside forces. About 700 drugs—or one-third of those approved by the US Food and Drug Administration—target these receptors, the firm says.

Many of these medicines arrived in the 1990s and early aughts, after drugmakers harvested “low-hanging fruit,” Lefkowitz says. But commercialization slowed because the complexity and transmembrane nature of GPCRs made them difficult to isolate and probe outside cells.

Septerna’s series A round will advance a pipeline of small-molecule drugs aimed at difficult-to-reach receptors, a new phase in Lefkowitz’s career after nearly 5 decades of studying GPCRs. “In a million years I couldn’t have imagined back in the ‘70s that this is where the field would be,” he says.

Septerna’s technology platform, called Native Complex, grew out of Lefkowitz’s research. The technology isolates GPCRs outside of the cell, allowing researchers to more easily design compounds that bind to families of GPCRs.

Lefkowitz—a professor of medicine, biochemistry, and chemistry at Duke University—initially resisted commercializing the technology. “I’m a quintessential academic. I’m not very entrepreneurial,” he says. But then came a serendipitous conversation with Jeffrey Finer, a partner at the venture capital firm Third Rock Ventures, which led the funding round. Finer is Septerna’s CEO and a co-founder.

Finer, who was curious about where the GPCR field stood, liked what he heard from Lefkowitz and his postdocs at Duke. But he encouraged them to think bigger. Taking his advice, Lefkowitz and team paired the Native Complex platform with computational and structure-based drug design techniques that have matured since Leftowitz’s Nobel-winning work. The company, which was founded in 2020 and has been operating in stealth mode, advanced the approach.

“We think we have a technology platform that is very unique . . . one that we think can really set off a whole new era of drug discovery,” Finer says.

Although he was initially reticent, Lefkowitz says building a company based on his research appeals to him as a former physician who cherished in-person care. “I loved clinical work, I loved being able to affect the lives of people who were ill. So, something like this gives me a chance to really do that, and on an even broader scale.”

But the company has a ways to go. Septerna’s programs target undisclosed diseases and are in the discovery stage. Clinical trials won’t start for a couple years. “We think there’s an opportunity down the road to become a company that not only has a mature clinical portfolio, but also is a company that can take things all the way to the market in some cases,” Finer says.

Based in San Francisco, Septerna already has more than 20 employees, a number that’s expected to double by year’s end. It’s not alone. The start-ups Tectonic Therapeutic and Confo Therapeutics, for example, are targeting GPCRs with biologics.

Finer says working with small molecules gives Septerna an advantage over firms developing biologic drugs. “If you can develop a small molecule, then it would almost certainly be better than a biologic in most applications,” he says.