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

Platform innovation and portfolio strategy

• Developed the Native Complex Platform to enable rapid, structure-based GPCR drug discovery, solving over 150 GPCR structures and identifying novel binding pockets for targeted modulation.

• Focused on targets with strong biological and clinical validation, prioritizing programs with early clinical readouts and significant unmet needs.

• Maintains a therapeutic area-agnostic approach, initially targeting endocrinology, immunology, inflammation, and metabolic diseases.

• Employs robust selectivity and preclinical testing to minimize off-target effects and leverages computational and DNA-encoded library screening.

• Well-capitalized with an IPO and Novo deal, supporting operations into at least 2029.

Lead programs and clinical progress

• SEP-479, an oral PTH receptor agonist for hypoparathyroidism, is entering phase I trials in H1 2025, with preclinical data showing normalization of calcium and phosphate in animal models.

• SEP-479 is structurally distinct from a prior candidate and has favorable PK, supporting once-daily dosing; phase I will focus on safety, PK, and on-target effects, with results expected late 2025 or early 2026.

• 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; preclinical models show potent inhibition of mast cell activation.

• SEP-631 is positioned as a once-daily oral therapy with a slow off-rate and insurmountable antagonism, aiming for broad application in dermatological and non-dermatological mast cell-driven diseases.

• TSHR NAM program for Graves' disease and thyroid eye disease is in lead optimization, showing reversal of disease in animal models and inhibition of diverse patient autoantibodies.

Market opportunities and business development

• Hypoparathyroidism market in the US is robust (70,000–80,000 patients), with a shift toward oral therapies due to patient preference and long-term health considerations.

• SEP-479 aims to address both therapy-naive and switch patients, offering an alternative to injectables and reducing kidney risks from high calcium intake.

• SEP-631 targets chronic spontaneous urticaria as the initial indication, with plans to explore additional mast cell-driven diseases in a capital-efficient manner.

• Novo Nordisk collaboration covers GLP-1, GIP, glucagon receptors, and two undisclosed targets, with Novo funding all R&D and offering milestone and royalty payments.

• Ongoing business development is opportunistic, with a focus on maximizing pipeline value through selective partnerships while prioritizing internal execution.