Septerna files for IPO on strength of preclinical data, vision for expanding GPCR landscape

Septerna is about to find out how a biotech without “any meaningful clinical data” fares in the late 2024 IPO market. The G protein-coupled receptor (GPCR) specialist is asking investors to fund development of its lead hypoparathyroidism candidate through phase 2 before it shares initial data in humans.

Biotechs frequently went public on the strength of animal data in the IPO boom years, but the class of 2024 is mostly made up of more mature companies. Septerna’s rise has more in common with the old model. The biotech was set up in 2021, exited stealth with $100 million and a high-profile co-founder in 2022, then added $150 million in a series B round in 2023 before announcing yesterday its intention to go public.

Investors who take the plunge will back a pipeline led by SEP-786, an oral small molecule PTH1R agonist for hypoparathyroidism. PTH1R has historically proven tough to drug with small molecules, leading other companies to develop injectable peptides to activate the receptor.

Using a platform for isolating functional native GPCR proteins outside of cells, Septerna has discovered a small molecule that could offer hypoparathyroidism patients an oral alternative to lifelong injections. The biotech believes SEP-786 is the only clinical-stage oral small molecule PTH1R agonist. SEP-786 could compete against injectables such as Ascendis Pharma’s Yorvipath and AstraZeneca’s eneboparatide.

Septerna said SEP-786 was generally well tolerated in preclinical tests and showed potent and selective activation of PTH1R in human, dog and rat receptor in vitro models. The small molecule controlled serum calcium levels within the normal range over a 28-day dosing period in a preclinical animal model of hypoparathyroidism.

A phase 1 study is underway to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SEP-786. However, investors will need to wait until around the middle of 2025 to see preliminary data on how the molecule performs in humans.

With $155.7 million in cash, equivalents and marketable securities at the end of June, Septerna said the IPO money will fund SEP-786 through phase 2 while supporting its MRGPRX2 program for chronic spontaneous urticaria until the end of phase 1.

Septerna’s current cash pile includes $47.6 million it received from Vertex in return for a GPCR program. The deal includes a potential payment tied to a research milestone. Septerna said “the variable consideration related to this milestone payment was determined to be improbable of receipt at this time.”