Septerna (SEPN) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Pipeline and platform

• GPCR-focused discovery platform has advanced four programs: SEP-479, SEP-204, SEP-631 and an early osteoporosis program.

• SEP-631, an MRGPRX2 negative allosteric modulator, completed Phase I; mast cell indications are under evaluation.

• Osteoporosis program uses a short-acting PTH receptor agonist approach; discovery-stage work is underway.

• Novo collaboration spans five targets and four concurrent programs, which were described as progressing well.

SEP-479 for hypoparathyroidism

• Oral small-molecule PTH receptor agonist is in Phase I; Q1 2027 readout is expected.

• SAD data showed a 3–4-day half-life across tested cohorts; MAD dosing was extended to 14 days to approach steady state.

• Healthy-volunteer study assesses safety, tolerability, PK, endogenous PTH and calcium; anticipated biomarker changes include ~50% lower endogenous PTH and a 0.3–0.5 mg/dL calcium increase.

• If Phase I finishes in Q1 2027, direct entry into a patient Phase II is planned for H2 2027; chronic animal safety studies have started to support potential open-label extension.

• Phase II is intended to identify starting dose and titration approach across two or three starting doses, informing the Phase III dose.

SEP-204 for Graves’ disease and thyroid eye disease

• Newly announced oral TSH receptor negative allosteric modulator blocks receptor activation even with Graves-derived autoantibodies; selectivity over FSHR and LHR exceeds 1,000-fold.

• Rat data showed lower doses normalized thyroid hormone levels while the high dose suppressed them, suggesting potential dose flexibility; K1-70 served as a positive control in mouse-model work.

• In an eight-week antibody-driven mouse model, treatment reversed thyroid histology and size changes and showed reversal of proptosis.

• GLP toxicology studies in rats and dogs are complete; clinic entry is targeted for Q1 2027, with a projected human half-life of 20–40 days.

• Targeting both Graves’ disease and thyroid eye disease, the once-daily oral approach aims to offer an alternative for patients who relapse on or cannot tolerate antithyroid drugs.