Septerna (SEPN) 43rd Annual J.P. Morgan Healthcare Conference 2025 summary

Platform Innovation and Strategy

• Native Complex Platform enables rapid, structure-based GPCR drug discovery, unlocking previously intractable targets and supporting rapid lead optimization, with <1 year from chemistry initiation to animal model activity.

• Platform allows high-resolution 3D structure determination, identification of novel binding pockets, and screening of billions of compounds via computational and biophysical approaches.

• Programs span endocrinology, immunology, inflammation, and metabolic diseases, targeting both peptide GPCR agonists and allosteric modulators.

• Vertex acquired a discovery-stage program in 2023 for $47.5M upfront, validating platform value.

• Leadership team includes proven experts in GPCR drug development and company building.

Pipeline Highlights and Clinical Progress

• SEP786, an oral PTH receptor agonist for hypoparathyroidism, is in phase 1 with mid-year data expected; preclinical models show normalization of serum calcium and favorable safety.

• SEP631, a negative allosteric modulator of MRGPRX2 for mast cell diseases, is in IND-enabling studies and expected to enter the clinic in 2025; demonstrates potent inhibition in humanized models.

• Early-stage programs include a TSH receptor NAM for Graves' disease and thyroid eye disease, showing universal inhibition of patient-derived antibodies and reversal of disease markers in animal models.

• Incretin receptor agonist program leverages a novel binding pocket for multi-receptor activity, with preclinical data showing additive weight loss effects and both single- and multi-agonist leads under optimization.

• All programs are wholly owned and address multi-billion dollar market opportunities, with rapid progression enabled by the platform.

Clinical and Commercial Outlook

• SEP786 phase 1 data will include safety, PK, calcium, and PTH biomarkers; sustained calcium increases and reciprocal PTH reductions in healthy volunteers would support proof of concept.

• Oral SEP786 offers a convenience advantage over injectable therapies and could benefit mild to moderate hypoparathyroidism patients, potentially reducing reliance on calcium and vitamin D supplements.

• Preclinical studies show no off-target toxicity for SEP786, and dosing strategy aims for chronic use without frequent up-titration.

• SEP631 has a differentiated safety and pharmacokinetic profile, with plans for phase 1 initiation and biomarker-driven proof of concept.

• Ongoing optimization and expansion of the pipeline are anticipated, leveraging the platform's capabilities for future growth.