NMRA: Highlights from the RBC Healthcare Conference

Research evidence excerpt

NMRA: Highlights from the RBC Healthcare Conference

ss CGI/

NPI in a pt population comparable to Rexulti/Auvelity pivotal studies, with what mgmt characterized as a superior tolerability

profile; MAD extension data expected 2H26, followed by a ph.II dose-ranging study.

• '511 is modeled at 93-97% V1aR receptor occupancy at 20mg BID vs. ~70-90% for Roche’s balovaptam at 10mg - we think this

differentiation could be important as the program advances; broader indication options mentioned by mgmt include GAD, SAD,

and PTSD; the aggression link (azervan precedent, Fragile X enrichment study ongoing) may also support the AD agitation thesis

mechanistically.

• Mgmt believes '215 is only NLRP3i to show semaglutide-like weight loss induction in DIO models and mgmt underscored that

this effect was likely due to '215's central activity and believe that '215 will need to be at IC90 over 24 hrs to have meaningful

effect on weight loss; peripheral NLRP3 inhibition has demonstrated other benefits (improvements in hsCRP and IL-6) from other

sponsored studies and we think that these could be class effects that translate to '215 as well.

• Mgmt noted that the for-cause audit for '215 is ongoing; events in the small # of animals appeared correlated with procedural

errors and were not dose-dependent or molecule-linked in their view - we continue to see this as potentially resolvable, though

it remains a near-term overhang until more data are available.

• We sensed significant excitement from mgmt around '898, their M4 PAM: an 80-100 hr half-life could be an important

differentiator in schizophrenia where compliance is a significant challenge (assuming, in our view, that dosing is thoughtfully

optimized), and variability in human PK observed to date is extremely low.