Neumora Therapeutics (NASDAQ:NMRA) executives highlighted new clinical-scale analyses for NMRA-511 in Alzheimer’s disease (AD) agitation and reviewed pipeline milestones during a presentation at the Guggenheim Emerging Outlook Biotech Summit 2026.
NMRA-511: Additional Phase 1b analyses in AD agitation
President Josh Pinto said the company shared additional data from a phase 1b “signal-seeking” study of NMRA-511 in AD agitation, following results previously disclosed last month. Pinto emphasized that the study was not powered for statistical significance and was designed to estimate effect size to inform future development.
As the company continued analyzing the dataset, Pinto said results were “highly consistent” across additional clinician- and caregiver-relevant scales. The new data highlighted included:
- CGI-S (agitation): In the prespecified elevated-anxiety subgroup, NMRA-511 showed effect sizes of 0.78 at week six and 0.38 at week eight, with Pinto noting benefit continued accruing over time.
- NPI agitation/aggression: In the elevated-anxiety subgroup, NMRA-511 showed effect sizes of approximately 0.46 at week eight. Pinto said this measure is important for treatment goals such as delaying time to institutional care and reflects caregiver distress.
Pinto also reviewed baseline characteristics, noting the total study population was generally balanced except for baseline RAID (anxiety) scores, which favored placebo. He suggested that balancing baseline RAID in future trials could potentially increase the treatment effect in the overall population and said the company intends to balance and stratify for this element in future studies.
Elevated anxiety subgroup and mechanistic rationale
In a prespecified analysis of patients with elevated baseline anxiety, Pinto said NMRA-511 produced a 20.1-point reduction on the CMAI total score at week eight, corresponding to a Cohen’s d effect size range of 0.51–0.64. He also pointed to a robust effect on the CMAI aggression subfactor, reporting a Cohen’s d effect size of 0.82, and noted that other sponsors have indicated FDA interest in CMAI subscale data.
Asked why the elevated-anxiety subgroup showed a clearer signal than the total population, Pinto said company market research suggests anxiety and agitation fall within an overlapping symptom domain that can evolve as disease progresses, with anxiety presenting earlier and later manifesting as aggression and agitation. He cited epidemiology estimates that 60%–70% of AD patients have agitation, and said market research suggests 60%–70% also have anxiety, with “pretty consistent overlap” between the two.
Chief Scientific Officer Nick Brandon discussed the scientific rationale, describing a preclinical literature linking vasopressin and the V1a receptor to stress and anxiety. Brandon also cited clinical observations in healthy volunteers in which intranasal vasopressin increased behaviors linked to stress and anxiety that could be reduced with a V1a antagonist. He added there are clinical data in conditions where a V1a antagonist impacts anxiety and “importantly, aggression,” which he said was a key reason the company pursued AD agitation.
Next steps for NMRA-511: higher-dose work and pivotal planning
Pinto said Neumora plans to initiate and complete a multiple-ascending-dose (MAD) extension cohort testing higher doses in 2026, then move into pivotal studies in 2027. He said the company also intends to transition from a twice-daily (BID) formulation to a once-daily (QD) extended-release formulation for pivotal studies, and stated this would extend intellectual property runway, moving an estimated composition-of-matter loss of exclusivity from 2042 to 2046.
On dose selection and target engagement, Pinto said there is no ligand available to run formal PET receptor occupancy studies for V1a in humans, so occupancy estimates rely on modeling. He said pharmacokinetics continued to progress from 20 mg to 40 mg in MAD studies and that modeling suggested “98%-ish” receptor occupancy at those levels, while emphasizing the uncertainty inherent in the model. Pinto said the company believes higher doses could improve pharmacokinetics and central target engagement, and said the company has safety margins to explore higher dosing.
On safety, Pinto said the company did not observe typical CNS tolerability issues such as headaches at a higher rate on active drug than placebo and addressed a single serious adverse event (SAE) of hyponatremia. He said there were confounding factors, including the patient’s age, a potential urinary tract issue, and circumstances around the event, and added the company did not view hyponatremia as necessarily mechanistic or drug-related based on what it has seen.
NLRP3 inhibitor NMRA-215: obesity thesis and upcoming data
In a separate discussion focused on the company’s NLRP3 program, Brandon said Neumora’s view is that driving weight loss with NLRP3 inhibition requires high levels of inhibition—IC90 over 24 hours—in the brain, particularly the hypothalamus, which he said regulates feeding circuitry. He also discussed peripheral effects, such as impacts on cardiovascular biomarkers including hsCRP and IL-6.
Brandon said the company believes NMRA-215 differentiates based on brain penetration and durability of brain exposure, referencing measures such as Kpuu (free drug in brain versus plasma), permeability, and a low risk of P-glycoprotein efflux. Pinto added that the company views the diet-induced obesity (DIO) model as among the most translatable preclinical models for weight loss and said the field is awaiting a highly CNS-penetrant NLRP3 inhibitor to test the hypothesis clinically.
On expected updates, Pinto said the company plans to present biomarker data in the third quarter, including evidence that NMRA-215 can achieve IC90 coverage in the brain, which he said is central to the weight-loss thesis. He also said the company expects to look at cardioprotective biomarkers such as CRP and provide additional clinical-study details as the program enters the clinic.
Discussing commercial positioning, Pinto said he expects GLP-1s to be established as backbone therapy by the early 2030s and outlined potential opportunities for NMRA-215 in combinations or “incretin-sparing” approaches that reduce incretin dose to lessen gastrointestinal adverse events while maintaining weight loss. He also described interest in a maintenance paradigm—switching from GLP-1 therapy to an NLRP3 inhibitor to maintain weight loss while potentially reducing GLP-1-related side effects—and said the company has demonstrated combination data in the DIO study.
Broader pipeline: M4 PAMs, KOASTAL timing, and cash runway
Brandon said Neumora has two M4 positive allosteric modulators (PAMs), NMRA-861 and NMRA-898, in phase 1 (SAD/MAD) studies. He said the company expects a mid-year 2026 update and anticipates advancing at least one compound into a proof-of-concept study, with decisions informed by factors such as CNS penetration, PK variability, CSF exposure measurements, and ongoing long-term toxicology studies.
On navacaprant and the KOASTAL program, Pinto said KOASTAL 2 and KOASTAL 3 are expected to read out in a combined joint analysis in the second quarter of 2026. He said the company opted to maximize enrollment—up to roughly 25% over-enrollment per protocol—citing higher screen-fail rates following implementation of SAFER and VCT and a belief that these changes are resulting in a higher-quality patient population.
Finally, Pinto said the company expects its current cash position to support operations into the third quarter of 2027, including funding for the catalysts discussed: the KOASTAL 2 and 3 readouts, the mid-year 2026 M4 update, and development activities for NMRA-215 and NMRA-511.
About Neumora Therapeutics (NASDAQ:NMRA)
Neumora Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on developing precision therapies for disorders of the central nervous system. The company applies an integrated approach that combines advanced biological insights, single-cell genomics and machine learning to accelerate the discovery and development of novel treatments for neurological and psychiatric diseases.
Neumora’s product pipeline spans small molecules, biologics and gene-based modalities targeting areas of high unmet need such as neurodegenerative conditions, mood and anxiety disorders, neuropathic pain and movement disorders.
