Neumora Therapeutics, Inc. · NASDAQ:NMRA
Neumora Therapeutics — Investor Day (October 2025)
48 slides from Neumora Therapeutics's investor day presentation, Oct 27, 2025
Slide 1: Novel Mechanisms, Better Medicines
Novel Mechanisms, Better Medicines R&D Day | October 27, 2025
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements about Neumora Therapeutics, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including statements related to: Neumora’s intention to redefine neuroscience drug development by
Slide 3: Today's presenters
Today’s presenters Helen Rubinstein Paul Berns Joshua Pinto, Ph.D. VP, Investor Relations Chief Executive Officer President and Communications Nick Brandon, Ph.D. Bill Aurora, Pharm.D. Anton P. Porsteinsson, M.D. Chief Scientific Officer Chief Operating & William B. and Sheila Konar Professor Develo
Slide 4: Agenda
Agenda Neumora’s Mission Paul Berns NMRA-215 for the Josh Pinto, Ph.D. Treatment of Obesity Nick Brandon, Ph.D. Bill Aurora, Pharm.D. NMRA-511 in Alzheimer’s Disease Agitation Fireside chat with Anton P. Porsteinsson, M.D., Director, University of Rochester Alzheimer’s Disease Care, Research and Edu
Slide 5: Neumora's Mission
Neumora’s Mission Paul Berns, Chief Executive Officer, Neumora 5
Slide 6: Our Mission
Our Mission We are focused on redefining neuroscience drug development by bringing forward the next generation of novel therapies that offer improved treatment outcomes and quality of life for patients 6
Slide 7: Advancing a leading neuroscience pipeline
Advancing a leading neuroscience pipeline PROGRAM INDICATION Target/Mechanism U.S. Prevalence Preclinical Phase 1 Phase 2 Phase 3 Major Depressive Navacaprant Disorder KOR Antagonist Broad pipeline 21M addressing some of the NMRA-511 Agitation in Alzheimer’s Disease V1aR Antagonist most prevalent di
Slide 8: Multiple catalysts expected over next 12 months
Multiple catalysts expected over next 12 months KEY MILESTONES TODAY Advance Advance Navacaprant Initiate Phase 1 NMRA-215 Phase 1 NMRA-861 NMRA-898 KOASTAL-2 studies of NMRA-215 human POC data to the clinic to the clinic topline data (1Q26) (2026) (2Q26) NMRA-511 Phase Navacaprant Provide M4 NMRA-2
Slide 9: NMRA-215 Program Overview
NMRA-215 Program Overview Joshua Pinto, Ph.D., President, Neumora 9
Slide 10: Obesity represents one of the greatest public health challenges
Obesity represents one of the greatest public health challenges And yet, NLRP3 inhibition By 2030, Significant May address unmet opportunity remains needs 1.13 BILLION people worldwide will be living Approved incretin therapies offer weight NLRP3 inhibition may offer benefit across with obesity1 los
Slide 11: NMRA-215 demonstrated best-in-class monotherapy weight loss up to 19%
NMRA-215 demonstrated best-in-class monotherapy weight loss up to 19% KEY DESIGN ELEMENTS RESULTS Monotherapy Pilot Study • Evaluate of NMRA-215 weight loss potential 16% body weight loss with NMRA-215 monotherapy Monotherapy: 15% body weight loss with semaglutide- Mono & Combination Therapy like in
Slide 12: NMRA-215 in Obesity
NMRA-215 in Obesity Nick Brandon, Ph.D., Chief Scientific Officer, Neumora 12
Slide 13: Multiple factors drive NLRP3-mediated inflammation resulting in disease
Multiple factors drive NLRP3-mediated inflammation resulting in disease NLRP3 ACTIVATION DRIVERS DISEASES ASC NLRP3 Caspase-1 NLRP3 inflammasome complex Diet (e.g., lipids) Cardiometabolic (obesity) Environment Neurodegeneration (Parkinson’s) Genetics pro-caspase-1 pro-caspase-1 Monogenic / autoimmu
Slide 14: CNS penetrant NLRP3 inhibition provides broad benefit
CNS penetrant NLRP3 inhibition provides broad benefit System Drug Impact Outcome CNS Reduce Reduced appetite and neuroinflammation drive body weight loss in the brain Potential treatment benefits driven by both CNS and Protect organ Reduce the risk of Periphery comorbidities. peripheral and vascular
Slide 15: Higher Brain Exposure
NMRA-215 has an optimized pharmacological profile including best-in-class CNS exposure NMRA-215 is highly potent with low NMRA-215 is NMRA-215 is extensively characterized nM potency across a range of assays highly selective for NLRP3 and optimized for brain exposure Rat Kpuu1-4 NMRA-215 Assay Forma
Slide 16: Doses selected for DIO studies to determine target coverage
Doses selected for DIO studies to determine target coverage necessary for weight loss NMRA-215 dose selection Semaglutide dose selection Goal: Sustained IC90 target coverage for 24 hours Goal: Select two doses that allow for evaluation of different treatment Dose (BID) IC paradigms Target Dose 90 Mi
Slide 17: Monotherapy: Up to 19% weight loss with NMRA-215 with incretin-like induction
Monotherapy: Up to 19% weight loss with NMRA-215 with incretin-like induction Induction Confirming STUDY 1 Pilot Study STUDY 2 Full DIO Study STUDY 3 Study* Body Weight Change (%) Body Weight Change (%) Body Weight Change (%) 5 10 5 5 0 0 -2% -2% 0 -5 -5 -4% -7% -5 -6% -7% -10% -7% -10 -10 -10 -15 -
Slide 18: Class-leading weight loss demonstrated with NMRA-215
Class-leading weight loss demonstrated with NMRA-215 NMRA-215 VTX3232 VENT-02 BGE-102 NT-0796 NMRA-215 monotherapy NLRP3i (end of study) 15%–19% 2% 11% 6% 17% demonstrates best-in-class weight loss semaglutide (end of 17%–19% 12% 21%^ 5% 21% study) NLRP3i (Day 7) 9% / 14% 3% 8% 6% 7% NMRA-215 monoth
Slide 19: Combination therapy: Up to 26% weight loss with NMRA-215 + semaglutide
Combination therapy: Up to 26% weight loss with NMRA-215 + semaglutide NMRA-215 + Combined with 3 nmol/kg semaglutide NMRA-215 + Combined with 1 nmol/kg semaglutide Body Weight Change (%) Body Weight Change (%) 10 10 5 5 0 0 - 4% -5 - 4% -5 -6% -10 -10 -15 -12% -17% -15 -20 -21% -18% -20 -25 -26% -3
Slide 20: Class-leading weight loss demonstrated with NMRA-215
Class-leading weight loss demonstrated with NMRA-215 NMRA-215 VTX3232 VENT-02 BGE-102 NT-0796 NLRP3i 15%–19% 2% 11% 6% 17% NMRA-215 monotherapy demonstrates similar weight loss as semaglutide semaglutide 17%–19% 12% 21%^ 5% 21% NLRP3i (Day 7) 9% / 14% 3% 8% 6% 7% NMRA-215 monotherapy has best-in-cla
Slide 21: NMRA-215 matches semaglutide weight loss with higher-quality outcomes
NMRA-215 matches semaglutide weight loss with higher-quality outcomes Reduced food intake Matches semaglutide weight loss, while preserving equivalent to semaglutide lean mass Cumulative food intake (g) 70 62.65 g 60 54.26 g Fat Mass (% to baseline) Lean Mass (% to baseline) 51.26 g 20 0 50 -1 15 -2
Slide 22: NMRA-215 drove positive results across key biomarkers
NMRA-215 drove positive results across key biomarkers Improved liver health Improved cardiovascular/lipid profile Improved insulin sensitivity similar to semaglutide relative to semaglutide Liver Weight HDL Insulin Tolerance Test 2500 5 1200 equiv. p<0.0001 2000 1000 4 AUC (0-150min) equiv. (mmol/L*
Slide 23: Data supports utility of NMRA-215 as monotherapy and combination therapy
Data supports utility of NMRA-215 as monotherapy and combination therapy Upcoming 12-week DIO data to evaluate maintenance paradigm NMRA-215 as weight loss 1 monotherapy Up to 19% body weight loss with semaglutide- Dose-dependent body weight loss confirmed Preserved lean mass and improved metabolic
Slide 24: NMRA-511 Overview
NMRA-511 Overview Bill Aurora, Pharm.D., Chief Operating & Development Officer, Neumora 24
Slide 25: NMRA-511 is a best-in-class vasopressin 1a receptor antagonist
NMRA-511 is a best-in-class vasopressin 1a receptor antagonist with broad potential across neuropsychiatric disorders Rationale Vasopressin plays a role in the regulation of aggression, affiliation, stress and anxiety response Indication Agitation in Alzheimer’s disease Status Phase 1b study underwa
Slide 26: Alzheimer's disease agitation represents large market opportunity with significant unmet need
Alzheimer’s disease agitation represents large market opportunity with significant unmet need U.S. Adults with Alzheimer’s Disease (M)1 Agitation in 13M 14 Alzheimer’s disease 13 impacts a significant portion of the U.S. 12 >70% 11 of people with AD population; that 10 experience agitation at number
Slide 27: V1a receptor antagonists have therapeutic potential for reducing agitation symptoms
Several lines of evidence indicate that V1a receptor antagonists have therapeutic potential for reducing symptoms of agitation The vasopressin system modulates social-emotional, anxiety and threat-related behaviors across species Positive association between • V1aR expression patterns critically aff
Slide 28: NMRA-511 was safe and well-tolerated in healthy adults and elderly participants
NMRA-511 was safe and well-tolerated in healthy adults and healthy elderly participants Phase 1 PK profile Dose selected for Phase 1b to maximize receptor Healthy Adults occupancy over 24 hours 40 mg QD in healthy adults compared to 20 mg BID in healthy elderly participants Plasma Concentration of P
Slide 29: NMRA-511 signal seeking study in Alzheimer's disease agitation
NMRA-511 signal seeking study in Alzheimer’s disease agitation Part A: 2-Week Evaluation Period Part B: 8-Week Evaluation Period Enrolling People Enrolling Healthy Elderly Participants with Alzheimer’s Disease Agitation (ADA) NMRA-511 20 mg BID (n=6) NMRA-511 20 mg BID (n=44) R R 1:1 1:1 Placebo BID
Slide 30: Significant opportunity for a product with a differentiated benefit/risk profile
Significant opportunity for a product with a differentiated benefit/risk profile Simplified market segmentation and opportunities Rexulti and other atypical Safety antipsychotics have a boxed warning for the risk of death in elderly individuals with Mild side- effects dementia-related psychosis Auve
Slide 31: Fireside Chat
Fireside Chat Anton P. Porsteinsson, M.D., William B. and Sheila Konar Professor of Psychiatry, Neurology, Neuroscience, and Medicine; Director, Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester School of Medicine and Dentistry Bill Aurora, Pharm.D., Chief O
Slide 32: M4 PAM Franchise Overview
M4 PAM Franchise Overview Nick Brandon, Ph.D., Chief Scientific Officer, Neumora 32
Slide 33: M4 PAM franchise: Differentiated M4R PAMs for schizophrenia
M4 PAM franchise: Differentiated M4R PAMs for schizophrenia M4 Franchise Target Profile Pharmacology IP Neumora has multiple series Composition of matter patent of chemically distinct, highly extending to 2044+* selective M4 muscarinic receptor PAMs, including Epidemiology NMRA-861 and NMRA-898, Est
Slide 34: Why M4 PAMs
Why M4 PAMs 1 2 3 Validated Target Improvement over SOC Selectivity Preclinical data and clinical Non-selective muscarinic PAMs offer the benefits data in acute schizophrenia agents are associated with of greater selectivity supports M4 as a driver of a range of peripheral AEs antipsychotic activity
Slide 35: Preclinical and clinical data support M4 as a driver of antipsychotic activity
Preclinical and clinical data in acute schizophrenia support M4 as a driver of antipsychotic activity Activity of xanomeline (active component Clinical activity shown with a M4 PAM and of Cobenfy ) is dependent on M4R in mice selective M4 agonist Placebo 20 mg NBI-1117568 1Digby GJ, et al. J Neurosc
Slide 36: Non-selective muscarinic agents are associated with a range of peripheral AEs
Non-selective muscarinic agents are associated with a range of peripheral AEs M4 M1, M2, M3 M1, M2, M3 M1, M3 Cardiovascular Cardiovascular GI Tract Glands Transient increased BP Direct effect on cardiac Increased gastric Increased salivation & heart rate function – increased BP secretion & gastric
Slide 37: PAMs offer the benefits of greater selectivity
PAMs offer the benefits of greater selectivity Targeting the allosteric site To date the pharmacology PAMs allow for more precise specifically allows for greater of agonists targeting potentiation of M4, maintaining selectivity for M4 over other the orthosteric site are often the spatial and tempora
Slide 38: NMRA-861 and -898 have potential best-in-class potency and optimized brain penetration
NMRA-861 and -898 have potential best-in-class potency and optimized brain penetration NMRA-8611 NMRA-8981 Emraclidine M4 EC50 6 nM 13 nM 26 nM (human; cAMP)1 NMRA-861 and -898 potentially more potent than emraclidine across multiple assays M4 EC50 2 nM 8 nM 180 nM (human; Ca2+)1 NMRA-861 and -898 a
Slide 39: SAD/MAD studies evaluating NMRA-861 and NMRA-898
SAD/MAD studies evaluating NMRA-861 and NMRA-898 in healthy adults and people with stable schizophrenia SAD – Part 1 CSP Study Objectives Dose Cohorts Participants Randomization Dose 1, Dose 2, Part 1A Healthy adults 6:2 active:placebo Dose 3, etc. • Confirm once-daily dosing – based on PK profile i
Slide 40: Navacaprant
Navacaprant Bill Aurora, Pharm.D., Chief Operating & Development Officer, Neumora 40
Slide 41: The role of kappa opioid receptor antagonism in MDD
The role of kappa opioid receptor antagonism in MDD Navacaprant • The kappa opioid receptor (KOR) / dynorphin system is a well- characterized pathway, and results from preclinical studies support its potential to modulate depression, anhedonia, and anxiety • KOR system overactivation in response to
Slide 42: Near-term clinical development plan focused on MDD
Near-term clinical development plan focused on MDD with opportunity for further expansion PHASE 3 DEVELOPMENT PROGRAM IN MDD KOASTAL-1 KOASTAL-2 KOASTAL-3 Conducted in U.S. Conducted in U.S., Conducted in U.S. Topline data announced 01/25 Canada and Latin America and Europe Placebo-controlled, doubl
Slide 43: KOASTAL pivotal study design
KOASTAL pivotal study design KOASTAL Pivotal Efficacy Studies Navacaprant 80 mg QD Opportunity R to enroll in 1:1 Placebo QD KOASTAL-LT Randomized, double-blind treatment Baseline WK WK WK WK 1 2 4 6 Key Efficacy Assessments KOASTAL-1, KOASTAL-2, KOASTAL-3 Summary • Adults ages 18 – 65 diagnosed wit
Slide 44: Optimizing KOASTAL-2 and -3 Phase 3 studies based on KOASTAL-1 learnings
Optimizing KOASTAL-2 and -3 Phase 3 studies based on learnings from KOASTAL-1 Site Selection Medical Monitoring Screening Tools Target Enrollment Adjusted clinical sites Using clinician-rated Verified Clinical Trial Option included in included in studies, with Massachusetts General (VCT) screening K
Slide 45: Closing Remarks
Closing Remarks Joshua Pinto, Ph.D., President, Neumora 45
Slide 46: Multiple catalysts expected over next 12 months
Multiple catalysts expected over next 12 months KEY MILESTONES TODAY Advance Advance Navacaprant Initiate Phase 1 NMRA-215 Phase 1 NMRA-861 NMRA-898 KOASTAL-2 studies of NMRA-215 human POC data to the clinic to the clinic topline data (1Q26) (2026) (2Q26) NMRA-511 Phase Navacaprant Provide M4 NMRA-2
Slide 47: Q&A
Q&A MODERATER Helen Rubinstein Paul Berns Joshua Pinto, Ph.D. VP, Investor Relations Chief Executive Officer President and Communications Nick Brandon, Ph.D. Bill Aurora, Pharm.D. Anton P. Porsteinsson, M.D. Chief Scientific Officer Chief Operating & William B. and Sheila Konar Professor Development
Slide 48: Neumora
Y) Neumora