Septerna (SEPN) investor relations material

Pipeline and program updates

• Lead program 479, an oral PTH receptor agonist for hypoparathyroidism, is progressing with full phase I SAD and MAD data expected in Q1 next year, focusing on safety, PK, PTH suppression, and calcium increases.

• Additional programs include a thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator for Graves' and thyroid eye disease, and a new osteoporosis program requiring a shorter-acting molecule.

• MRGPRX2 program remains active, with a best-in-class negative allosteric modulator being evaluated in capital-efficient, indication-finding phase IIa trials.

• Novo Nordisk collaboration covers five cardiometabolic targets, with significant upfront and milestone payments and ongoing R&D reimbursement.

• The Native Complex Platform enables discovery of small molecules for difficult GPCRs, with robust IP protection and ongoing technological enhancements.

Clinical development strategy and learnings

• Phase I data for 479 is expected to be highly predictive for later-stage trials due to strong translational correlation in this target class.

• Oral administration of 479 is expected to improve adherence and expand use to milder patient populations compared to injectables.

• Lessons from prior molecule 786 led to enhanced safety screening, backup compound strategies, and earlier chronic toxicology studies.

• Both capsule and tablet formulations of 479 are being tested in phase I, with no major differences expected.

• Regulatory changes in osteoporosis now allow bone mineral density as a surrogate endpoint, enabling smaller, faster trials.

Forward-looking statements and milestones

• Key updates in the next 12–18 months include phase I data for 479, preclinical data for osteoporosis, and progress on TSHR and MRGPRX2 programs.

• The company may advance the osteoporosis program further in-house due to regulatory shifts, but may seek commercial partners for large-scale commercialization.

• Additional undisclosed programs are in early development and may be added to the pipeline as they mature.

• Updates on the Novo collaboration will be reflected in financials due to external communication controls.