SEPN: Itching for Upside Across G-Protein Coupled Receptors and Not-so-Rare Diseases; Imminent Competitor Read-Through from EVMN Is Just the Start – Initiating at BUY with a $52/share PT

Research evidence excerpt

SEPN: Itching for Upside Across G-Protein Coupled Receptors and Not-so-Rare Diseases; Imminent Competitor Read-Through from EVMN Is Just the Start – Initiating at BUY with a $52/share PT

Biotechnology June 11, 2026

Seamus Fernandez

seamus.fernandez@guggenheimpartners.com SEPN: Itching for Upside Across G-Protein Coupled Receptors and Not-so-Rare

617 859 4637 Diseases; Imminent Competitor Read-Through from EVMN Is Just the Start – Alana Lelo, Ph.D.

alana.lelo@guggenheimpartners.com Initiating at BUY with a $52/share PT

212 518 9955

Zach Dunn, Ph.D. Key Message: We are initiating coverage of Septerna, Inc. (SEPN) with a BUY rating and a $52/shr PT based on our high conviction zach.dunn@guggenheimpartners.com

617 859 4603 in multi-blockbuster potential across SEPN's oral small-molecule GPCR pipeline and optionality from the company's Native Complex

platform. Our thesis centers on two clinical-stage assets where we see material upside post positive Ph 1 (SEP-479) and Ph 2

Evan Wang (SEP-631) catalysts expected in the next 12-18 months. SEP-631, an oral MRGPRX2 negative allosteric modulator (NAM) with positive

evan.wang@guggenheimpartners.com Phase 1b data in hand, offers an oral alternative to biologics and Rhapsido's (NOVN) BTKi in CSU, addressing ~2M+ US patients 212 651 9756

uncontrolled on antihistamines. While SEP-631’s Ph 2 is planned to start in 2H26, the imminent readout of EVMN's EVO756 Phase

Colleen Garvey, Ph.D. 2 (June 2026) is a class-validating event; SEPN's Phase 2b is expected to read out 2H27/2028. Given our bullish stance on the X2

colleen.garvey@guggenheimpartners.com mechanism in CSU/CINDU and potentially other itch disorders, we model 50% risk-adjustment, yielding ~$1B WW risk-adjusted peak