Neumora Therapeutics (NMRA) 25th Annual Needham Virtual Healthcare Conference summary

Pipeline progress and clinical milestones

• Four programs are in or entering the clinic, with substantial progress expected this year.

• Navacaprant completed last patient in for phase III KOASTAL-2 and KOASTAL-3 studies in major depressive disorder; data expected in Q2.

• NMRA-511 for Alzheimer's agitation showed efficacy comparable to Rexulti with a better safety profile; phase II initiation planned for 2027.

• NMRA-898 prioritized in the muscarinic franchise after promising SAD data; SAD/MAD studies to complete in Q3, with phase Ia/Ib proof of concept to follow.

• NMRA-215 (NLRP3 inhibitor) for obesity validated in preclinical studies; clinical entry targeted for early 2027 after repeat tox studies.

Regulatory and study design updates

• FDA guidance allows for approval based on a single pivotal study with supportive evidence; positive results from either KOASTAL-2 or KOASTAL-3 could support a pre-NDA meeting.

• KOASTAL-2 and KOASTAL-3 studies were improved post-KOASTAL-1 with stricter patient screening, fewer sites, and expert involvement, increasing screen failure rates and confidence in patient selection.

• Studies are powered at 90% with 332 patients to detect a 3.2 placebo-adjusted change on MADRS.

Mechanistic and clinical differentiation

• Navacaprant targets anhedonia, a key symptom in MDD, with MADRS as the primary endpoint and SHAPS as a secondary endpoint.

• NMRA-511 aims for a broad label in AD agitation, leveraging robust efficacy in anxiety and NPI-A/A ≥4 populations, and intends to maintain a favorable safety profile.

• NMRA-215 is differentiated by CNS penetration, believed critical for obesity efficacy, and binds the NACHT domain of NLRP3.

• NMRA-898 offers once-daily dosing, strong target engagement, and low variability, with focus on schizophrenia and potential for broader muscarinic franchise expansion.