Neumora Therapeutics (NASDAQ:NMRA) outlined clinical and pipeline updates alongside its fourth-quarter and full-year 2025 financial results, highlighting multiple anticipated data catalysts in 2026 and providing additional detail on several preclinical and clinical programs.
Management highlights “catalyst-rich” 2026
Chief Executive Officer Paul Berns said 2025 included “important clinical progress and execution,” pointing to progress across the company’s pipeline, including NMRA-511 in Alzheimer’s disease agitation, the phase III navacaprant program in major depressive disorder (MDD), expansion of the company’s M4 positive allosteric modulator (PAM) franchise, and updated preclinical work for NMRA-215 in obesity.
NMRA-511: Additional Phase 1b analysis in AD agitation
Pinto said Neumora recently reported positive results from a phase 1b “signal-seeking” study of NMRA-511, an oral vasopressin 1A receptor antagonist being developed for Alzheimer’s disease (AD) agitation. He emphasized the study showed a “clinically meaningful effect size” and favorable safety and tolerability “with no reports of somnolence or sedation.”
On the call, the company highlighted new data from a pre-specified analysis in patients with a Neuropsychiatric Inventory agitation/aggression (NPI-AA) score of 4 or greater, which Pinto said aligns with enrollment criteria used in pivotal studies of Rexulti and Auvelity. Chief Operating and Development Officer Bill Aurora said this analysis included 53 patients and that NMRA-511-treated patients showed clinical benefit with a Cohen’s d effect size of 0.32 to 0.34 on the Cohen-Mansfield Agitation Inventory (CMAI) total score, “a similar magnitude to Rexulti.” Aurora also said the company observed an “unsurpassed effect size” across the CMAI Aggressive Behaviors subfactor and CGI-S agitation score in that population.
Aurora said the phase 1b was not powered for statistical significance and was designed to evaluate effect size across measures to inform future development. He added that the favorable tolerability in phase 1b provides an opportunity to test higher doses. Neumora plans a multiple ascending dose (MAD) extension, with data expected in the second half of 2026, and expects to initiate a phase II study in the first quarter of 2027.
In response to a question on effect size over time, Aurora said the effect size was “quite consistent” across timepoints. Pinto added that the new NPI-AA analysis supports a “well-established regulatory pathway” while “preserving the ability for a broad label” in AD agitation.
Navacaprant: Phase III KOASTAL-2 and KOASTAL-3 fully enrolled
Neumora’s phase III program for navacaprant, a kappa-opioid receptor antagonist being studied as monotherapy for MDD, has reached full enrollment. Aurora said KOASTAL-2 and KOASTAL-3 each enrolled more than 400 patients and are now fully enrolled, with a “joint top-line data readout” expected in the second quarter of 2026.
Aurora said the company incorporated “key learnings” from the prior KOASTAL-1 readout, including enhanced medical monitoring to verify appropriate patients, screening tools to rule out “professional patients,” and focusing on sites with MDD trial expertise. He added that screen fail rates were approximately 10% higher than KOASTAL-1, which management characterized as supportive of improved patient selection.
Management said the upcoming joint readout is expected to include:
- Top-line results for KOASTAL-2
- Top-line results for KOASTAL-3
- Pre-specified analyses including a post-optimization population of more than 450 patients enrolled after changes were implemented in early 2025
During Q&A, Aurora said Neumora believes “one positive study, either KOASTAL-2 or KOASTAL-3 plus supportive data,” would support requesting a pre-NDA meeting with the FDA. He said supportive evidence could come in “a variety of forms,” including measures such as anhedonia as measured by SHAPS and safety/tolerability in a large population.
M4 PAM and metabolic programs: NMRA-898 selected; NMRA-215 tox issue prompts repeat study
Neumora announced it has selected NMRA-898 as its lead M4 PAM program for development in schizophrenia. Aurora said NMRA-898 showed an approximately 80- to 100-hour half-life in humans in an ongoing phase I study, supporting once-daily dosing, and that exposures were dose-proportional with low variability. He also said the company observed “on-target changes in heart rate” that it views as pharmacodynamic evidence of target engagement.
Aurora said Neumora is conducting a MAD study of NMRA-898 in healthy volunteers and patients with stable schizophrenia, with objectives including identifying a maximum tolerated dose and confirming CNS penetration via CSF exposure. Data are expected in the second half of 2026. Management also said development of NMRA-861 has been paused, though Pinto said it remains a “viable compound for future indications.”
In the metabolic franchise, Chief Scientific Officer Nicholas Brandon reviewed new 12-week diet-induced obesity (DIO) mouse data for NMRA-215, the company’s brain-penetrant oral NLRP3 inhibitor being prioritized for obesity. Brandon said the study supports potential use in “mechanism of action switch and maintenance treatment paradigms.” He described results in which mice switched at week 8 from NMRA-215 plus semaglutide to NMRA-215 monotherapy maintained weight loss similar to semaglutide monotherapy through the full study duration. He also said NMRA-215 showed “sustained semaglutide-like weight loss” after switching from semaglutide to NMRA-215 at week 8.
However, management also disclosed “unexpected adverse findings” in a small number of animals in a separate 13-week rat toxicology study. Brandon said the observations were not dose-dependent, were not associated with a known molecule-related or on-target effect, and occurred alongside “documented study conduct issues.” He said the company opened a for-cause audit and has started dosing a repeat 13-week rat toxicology study at a different CRO. Brandon said Neumora has completed 28-day rat and dog and 13-week dog toxicology studies without similar findings and with margins management believes are sufficient to achieve IC90 brain concentrations.
Neumora now expects to bring NMRA-215 into the clinic in the first quarter of 2027. Pinto said the delay reduces 2026 spending on NMRA-215 and “will free up capital” for other areas.
Cash position and runway
Chief Financial Officer Michael Milligan said Neumora ended 2025 with $182.5 million in cash, cash equivalents, and marketable securities, and expects its current cash position to support operations into the third quarter of 2027. Milligan also said the company’s total net loss for 2025 was comparable to 2024, and directed investors to the company’s press release for additional financial detail.
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.
