Neumora Therapeutics (NMRA) investor relations material

Pipeline and clinical milestones

• Six clinical readouts are expected over the next 12 months across four main clinical-stage assets, all fully funded with a cash runway into 2027.

• NMRA-215, a NLRP3 inhibitor, showed class-leading weight loss in preclinical models and will enter clinical trials in Q1 2026, with human proof-of-concept data expected by end of 2026.

• NMRA-511 is advancing in a phase 1b study for Alzheimer's disease agitation, with a readout anticipated by year-end; the study uses the Cohen-Mansfield Agitation Inventory as the primary endpoint.

• The M4 PAM franchise has two molecules in clinical development, with phase 1 SAD/MAD data expected by mid-2026; these are optimized for CNS penetration to address antipsychotic needs.

• Navacaprant, a kappa opioid receptor antagonist, is progressing through KOASTAL-2 and 3 studies, with readouts in Q1 and Q2 2026, respectively.

Scientific rationale and differentiation

• NMRA-215's weight loss effect is attributed to achieving IC90 concentrations in the CNS, differentiating it from other NLRP3 inhibitors that lack sufficient brain penetration.

• Peripheral benefits such as improved cardiovascular and liver biomarkers are expected to be retained even if weight loss does not translate clinically.

• The vasopressin system is targeted in NMRA-511 for AD agitation, supported by preclinical and clinical evidence linking vasopressin to agitation and stress response.

• M4 PAMs are designed to overcome limitations of first-generation compounds by enhancing brain permeability and reducing efflux, aiming for better efficacy in neuropsychiatric indications.

Study design and operational improvements

• NMRA-215's first-in-human study will use a traditional early-phase obesity design, with dose escalation and 12-week monotherapy and combination arms.

• The NMRA-511 AD agitation study is a two-part, signal-seeking trial with multiple endpoints, including patient, physician, and caregiver perspectives.

• KOASTAL-2 and 3 studies for navacaprant have implemented stricter patient screening and monitoring to ensure appropriate enrollment and data quality.

• Operational changes include collaboration with Mass General Hospital and use of the VCT database to exclude professional study participants.