Septerna (SEPN) 44th Annual J.P. Morgan Healthcare Conference summary

Platform and portfolio overview

• Focused on GPCR drug discovery using the Native Complex Platform, enabling rapid identification and optimization of compounds for difficult-to-drug targets.

• Portfolio includes programs with early clinical readouts, targeting validated biological and clinical needs.

• Well-capitalized with cash runway into at least 2029, following an IPO and a Novo collaboration.

• Therapeutic focus spans endocrinology, immunology, inflammation, and metabolic diseases, but remains area-agnostic.

• Platform enables discovery of novel binding pockets and rapid structure-based design, solving over 150 GPCR structures to date.

Lead programs and clinical progress

• SEP-479, a PTH receptor agonist for hypoparathyroidism, is entering phase I trials in the first half of 2025, with IND-enabling studies completed and strong preclinical data.

• SEP-479 demonstrated normalization of serum calcium and phosphate in animal models and favorable PK/PD in monkeys.

• SEP-631, a negative allosteric modulator of MRGPRX2 for mast cell diseases, is completing phase I, with data to be presented at AAAAI in March.

• SEP-631 shows potent, insurmountable inhibition of MRGPRX2, with broad potential across dermatological and non-dermatological indications.

• TSHR program targets Graves' disease and thyroid eye disease with a negative allosteric modulator, showing reversal of disease in animal models and nearing candidate selection.

Market opportunities and strategy

• Hypoparathyroidism market estimated at 70,000–80,000 US patients, with unmet need for oral therapies due to drawbacks of current injectable and calcium-based treatments.

• SEP-479 aims to address both naive and switch patients, offering a convenient oral option with broad applicability.

• SEP-631's mechanism is differentiated by its insurmountable receptor inhibition and slow off-rate, with CSU as the initial indication and plans to explore additional mast cell-driven diseases.

• TSHR program aspires to provide a universal, disease-modifying therapy for both Graves' and thyroid eye disease, overcoming limitations of current treatments.

• Novo Nordisk collaboration covers multiple incretin and metabolic targets, with Novo funding all R&D and offering milestone and royalty payments.