Septerna (SEPN) investor relations material

Portfolio and platform overview

• Focused on GPCR drug discovery using the Native Complex Platform, enabling rapid identification and optimization of small molecule agonists for challenging targets.

• Pipeline includes parathyroid hormone receptor (PTH) agonists, MRGPRX2 mast cell program, thyroid stimulating hormone receptor, and incretin receptor agonists.

• Major collaboration formed with Novo Nordisk for multi-target incretin receptor program, with $195 million upfront and Novo covering all R&D costs.

Parathyroid hormone receptor program updates

• SEP-786 discontinued due to unexpected unconjugated bilirubin increases, traced to UGT1A1 inhibition, but no liver injury observed.

• SEP-479, a structurally distinct next-generation candidate, shows improved properties, no UGT1A1 inhibition, and effective normalization of calcium and phosphate in preclinical models at much lower doses.

• SEP-479 predicted to have a human half-life of 40–80 hours, supporting once-daily dosing; GLP-Tox studies in rats, dogs, and SINOS underway.

• Phase 1 trial for SEP-479 planned for first half of next year, aiming to demonstrate safety, PK, and relevant calcium increases in healthy volunteers.

• Development plan includes phase 1, small phase 2 for dose titration, and phase 3 pivotal trial.

MRGPRX2 (SEP-631) mast cell program

• SEP-631 in phase 1, using a skin challenge model to assess pharmacodynamic activity and skin penetration.

• Compound acts as an insurmountable negative allosteric modulator, fully inhibiting MRGPRX2 activation for extended periods.

• Targeting multiple mast cell-driven diseases, including chronic spontaneous urticaria, atopic dermatitis, and potentially non-skin conditions like asthma and migraine.

• Phase 2 strategy may pursue multiple indications in parallel; phase 1 data expected in first half of next year.