EVO756 Ph2b CSU Miss Disappointing, But SEP-631 Has Differentiated Profile

Research evidence excerpt

EVO756 Ph2b CSU Miss Disappointing, But SEP-631 Has Differentiated Profile

TD Cowen Septerna

Global Research June 29, 2026

charge" inflammation. The X2 ligand PACAP has also been shown to trigger migraine

via X2 as a primary receptor in mice, and human data has shown that PACAP infusion

induces migraine-like attacks in people with migraine. Lundbeck is also developing

bocunebart (PACAP inhibitor) for migraine.

Mgmt noted interest in migraine as a future indication for SEP631 and will provide

guidance for potential to pursue migraine by YE26. They noted the potential to run

smaller studies in migraine at high doses to see if they can gain confidence in

running a larger study.

Mgmt is also considering additional mast cell-driven diseases where tissue-resident

mast cells and MRGPRX2 play a central role, such as interstitial cystitis and asthma,

but expressed reservations about the merits of moving into atopic dermatitis.

SEP-479 (PTH1R Agonist) Ph1 SAD/MAD In HV Initiated In April With Data In Late

'26/Early '27

Septerna initiated a Ph1 SAD/MAD study in HV for SEP-479, its potent and selective

oral small molecule PTH1R agonist for hypoparathyroidism (HP) in April. Preclinical

data demonstrate robust normalization of serum calcium and favorable

pharmacokinetics across species, with projected once-daily dosing in humans. The

Ph1 HV study will assess safety, PK, and PD via changes in endogenous PTH and

serum calcium, with topline data expected in late 2026 or early 2027.

Mgmt expects that the half-life of the drug could be 40-80 hrs. They will have more

data over the summer that will help fine-tune the data timing. For example, if the half-

life is on the longer end, the MAD portion of the study could take longer, thereby

pushing the data into early '27.