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

Platform and technology

• Native Complex Platform enables rapid, structure-based GPCR drug discovery, supporting high-resolution 3D structure determination and screening of billions of compounds using computational and biophysical approaches.

• Platform has solved over 100 GPCR-ligand structures, unlocking difficult-to-drug GPCRs beyond the six subfamilies that dominate approved drugs.

• Achieved active compounds in animal models for all programs in under a year from medicinal chemistry start.

• Platform supports rapid lead optimization and pipeline expansion, validated by a $47.5M upfront acquisition by Vertex.

• Focused on addressing large, underserved markets with differentiated, first-in-class therapies.

Pipeline and programs

• SEP786, an oral PTH receptor agonist for hypoparathyroidism, is in phase 1 with data expected mid-2025, aiming to replace injectable therapies and address significant unmet need.

• SEP631, a negative allosteric modulator targeting MRGPRX2 for mast cell diseases, is in IND-enabling studies and expected to enter the clinic in 2025.

• Early-stage programs include a TSH receptor NAM for Graves' disease and thyroid eye disease, and a novel incretin receptor agonist program with multi-receptor activity.

• Each program targets large market opportunities and areas of unmet need, with early clinical readouts designed to rapidly assess proof of concept.

• Pipeline spans endocrinology, immunology, inflammation, metabolic, and other therapeutic areas.

Preclinical and clinical data highlights

• SEP786 normalized serum calcium in preclinical models and is being evaluated for safety, PK, calcium, and PTH biomarkers in healthy volunteers.

• SEP631 demonstrated complete inhibition of mast cell degranulation in humanized mouse models and primary human cells, with high potency and favorable safety profile.

• TSH receptor NAMs blocked activation by all patient-derived antibodies and reversed disease symptoms in preclinical Graves' disease models.

• Incretin program identified a novel binding pocket with high sequence similarity across GLP-1, GIP, and glucagon receptors, enabling development of mono, dual, and triple agonists.

• Oral incretin receptor agonists demonstrated weight loss in preclinical models, with both single- and multi-agonist leads under optimization.