Septerna (SEPN) Evercore ISI 8th Annual HealthCONx Conference summary

Platform and portfolio overview

• Focused on GPCR drug discovery using the Native Complex Platform, enabling rapid development of a portfolio with validated targets and early clinical readouts.

• Cash runway extends into at least 2029, supporting ongoing and future programs.

• Key programs include SEP-479 (PTH1 receptor agonist for hyperparathyroidism), SEP-631 (MRGPRX2 negative allosteric modulator for mast cell diseases), and a TSHR NAM for Graves' and thyroid eye disease.

• Collaboration with Novo Nordisk on a novel incretin receptor agonist program, leveraging a unique binding pocket for multi-receptor activation.

SEP-479 (PTH1 receptor agonist) development

• SEP-479 is structurally distinct from the discontinued SEP-786 and shows no UGT1A1 inhibition, with improved pharmaceutical properties.

• Demonstrated normalization of calcium and phosphate in a rat model at lower doses than SEP-786.

• Monkey PK/PD studies show 80% reduction in endogenous PTH and targeted increases in serum calcium, simulating healthy volunteer responses.

• IND-enabling studies completed in rats and dogs; cynomolgus monkey study ongoing, with clinical entry expected in the first half of next year.

• Low receptor occupancy is sufficient for efficacy, with titration required for individual patients; healthy volunteer data will inform patient dosing.

SEP-631 (MRGPRX2 negative allosteric modulator) progress

• High potency and broad inhibition across MRGPRX2 agonists, with a long residence time and insurmountable negative allosteric mechanism.

• Preclinical models show complete inhibition of mast cell activation and extravasation in humanized mice and primary human skin mast cells.

• Phase I trial underway with once-daily dosing; Icatibant skin challenge used in the MAD portion to assess efficacy at both low and high doses.

• Data from the trial expected in the first half of next year; plans to move directly into a controlled CSU study following positive results.

• Monitoring external data from competitors to benchmark efficacy and inform development strategy.