Septerna (SEPN) Cantor Global Healthcare Conference 2025 summary

Platform and strategy

• Native Complex platform enables rapid, structure-based drug discovery for GPCRs, overcoming historical challenges in isolating fully functional receptors.

• Platform supports discovery of both orthosteric agonists and allosteric modulators, expanding druggable GPCR targets.

• Focus on well-validated targets with early clinical readouts and significant market opportunities.

• Portfolio spans endocrinology, immunology, inflammation, metabolic diseases, and early-stage neurology.

• Strong financial position with capital to operate into at least 2029, bolstered by recent IPO and Novo Nordisk partnership.

Lead programs and clinical updates

• SEP-479, a next-generation oral PTH1R agonist for hypoparathyroidism, selected as new development candidate; demonstrates 40-fold lower effective dose and longer projected half-life than predecessor.

• SEP-786, the first PTH1R candidate, discontinued after phase 1 due to reversible unconjugated bilirubin increases linked to UGT1A1 inhibition; learnings informed SEP-479 design.

• SEP-479 shows no UGT1A1 inhibition or hyperbilirubinemia in preclinical studies and is well tolerated in 28-day GLP-tox studies; additional cynomolgus monkey study underway.

• Anticipated return to clinic with SEP-479 in first half of next year, pending successful ongoing studies and regulatory steps.

Additional pipeline highlights

• SEP-631, a negative allosteric modulator of MRGPRX2, targets mast cell-driven diseases like chronic spontaneous urticaria; phase 1 trial underway with up to 150 healthy volunteers.

• SEP-631 demonstrates potent, insurmountable inhibition in humanized mouse and primary human mast cell models, with favorable PK and safety profile.

• Phase 1 includes pharmacodynamic skin challenge using Icatibant; SAD and MAD data expected in first half of next year.

• Discovery-stage TSH receptor program aims for a universal small molecule therapy for Graves' disease and thyroid eye disease, showing reversal of disease phenotypes in animal models.