Septerna has secured $150 million in a series B fundraise, money that will go toward two newly unveiled programs including moving its first G-protein-coupled receptor (GPCR) drug into the clinic.
The San Francisco-based biotech roped in nine new investors for the series B, CEO and co-founder Jeffrey Finer, M.D., Ph.D., told Fierce Biotech in an interview. They included serial biotech investor RA Capital Management, which led the financing round.
The gaggle of new supporters join Septerna’s seven existing investors, all of which have come back for round two. One of the original investors is the VC firm Third Rock Ventures, where Septerna was incubated and Finer has been a venture partner since 2016.
“Our story really resonated with the investment community,” Finer said, adding that he thinks the reason investors saw value is Septerna’s programs “have legs” to get into the clinic.
Septerna launched early last year with $100 million in hand and a mission to redesign the field of GPCR drug discovery. The company was co-founded by Nobel laureate Robert Lefkowitz, M.D.—who Finer described as the father of the GPCR field.
Nearly a third of all approved drugs target GPCRs, proteins that help regulate most aspects of human physiology, including sight and blood pressure. However, plenty of potential therapeutic GPCR targets remain undrugged, Finer explained. To unlock new opportunities and tackle both validated GPCRs and those that have so far proved out of reach, Septerna has built out a platform it's christened Native Complex.
The platform uses advanced bioengineering outside of the cell environment to recapitulate GPCRs with their native structure, function and dynamics. The goal is to allow for industrial-scale drug discovery for all GPCR targets—something that has never been done before.
Septerna hopes its tech will allow it to create therapies that bind to allosteric sites, which are the places on the protein's surface other than its most active, orthosteric site. Very few approved GPCR-targeting drugs bind to allosteric sites, opening up a huge opportunity for Septerna, according to Finer.
Against this backdrop, the company hopes to channel its series B funds into two newly revealed programs, both of which are oral small-molecule medicines taking aim at hard-to-drug GPCR targets.
The biotech’s lead program targets the parathyroid hormone 1 receptor (PTH1R) and is aimed at treating hypoparathyroidism, a condition in which parathyroid glands don't produce enough calcium. Symptoms can include muscle aches and spasms, and severe cases can lead to seizures, irregular heartbeat and kidney failure.
Approved treatments for hypoparathyroidism include supplements, which only partially address the deficiency, Finer explained. In May, the FDA issued a manufacturing-related complete response letter rejecting Ascendis’ hypoparathyroidism drug, a hormone replacement therapy that would require daily injections.
Instead of an injectable, Septerna wants to develop the first oral small-molecule PTH1R agonist designed for all patients with hypoparathyroidism, Finer said. The $150 million will help propel the biotech’s lead program into a phase 1 clinical trial.
The company also unveiled a second preclinical program that targets the thyroid-stimulating hormone receptor to treat Graves' disease. The autoimmune disorder can cause an overactive thyroid, known as hyperthyroidism.
Historically, patients with the disease have relied on anti-thyroid treatments. Recent breakthroughs in the space include Horizon Therapeutics’ Tepezza, which is approved to treat thyroid eye disease, though it's only used for patients with severe iterations of the condition and requires several injections for a full course of treatment.
“Our drug, we think, could be completely disease-modifying,” Finer said. The biotech also has three other unnamed programs in its preclinical pipeline.