Next Steps On X2 & Broader Portfolio

Research evidence excerpt

Next Steps On X2 & Broader Portfolio

June 29, 2026

●Given the EVMN results, SEPN is no longer likely to conduct a large P2

trial in CSU alongside a basket-approach to other indications. Instead,

CSU will likely be folded in the exploratory study.

●SEPN makes a good case that MRGPRX2 may still be an important

driver of CSU, but one requiring deep target suppression to achieve

disease improvement.

●Unfortunately, with limited data from the EVMN program, it's

not yet possible to know for sure if they did achieve adequately

deep MRGPRX2 supression to improve outcomes - but it's

prudent to work with the assumption they did.

●Since EVMN is stopping the CSU program, it also doesn't seem

like they saw any favorable plausible signals of effect in subsets

of patients, which is one of the biggest issues we see for this and

potentially other X2 indications - specifically, figuring out which

patients may be most likely to respond to pathway inhibitors.

●As such, while there theoretically may still be some opportunity for

SEPN's '631, the company will likely limit resource allocation for '631

for CSU as it probes around other potential applications (we're keen to

see if there is utility in interstitial cystitis or migraine headache). And,

notably, the EVMN data for CindU was quite strong so this could be an

indication worth considering, even if it is a smaller market than CSU.

SEPN shares only sold off modestly today (down 7%), as the stock

is buffeted by the PTH and TSHR inhibitor programs as well as the

collaboration with NVO for oral obesity drugs.

●And while we see potential for considerable value creation with any

of those programs, we also remain cognizant of the broader platform

of the company and look forward to seeing what other rabbits SEPN