Neumora Therapeutics' 2025 Q4 Call: Clinical Timelines, Safety Data, and KOASTAL Resumption Guidance Clash

Date of Call: Mar 30, 2026

Guidance:

• NMRA-511 MAD extension cohort data expected in second half of 2026; phase II study initiation planned for Q1 2027.
• Navacaprant KOASTAL-2 and KOASTAL-3 top-line data readout expected in Q2 2026.
• NMRA-898 MAD study data expected in second half of 2026.
• NMRA-215 repeat 13-week rat tox study complete; clinic entry expected in Q1 2027.
• Cash position expected to support operations into Q3 2027.

Business Commentary:

Clinical Progress and Pipeline Development:

• Neumora Therapeutics reported positive results from its phase I-B study for NMRA-511, showing a clinically meaningful effect size in patients with Alzheimer’s disease and a favorable safety profile.
• The company is advancing NMRA-511 with plans for a MAD extension cohort and a phase II study, indicating confidence in its potential for treating Alzheimer’s disease agitation.

Navacaprant Phase III Trials:

• KOASTAL-2 and KOASTAL-3 studies for navacaprant in major depressive disorder are fully enrolled with over 400 patients each, with data expected in Q2 2026.
• The trials incorporated optimizations following key learnings from prior studies, which are expected to result in a stronger dataset.

NLRP3 Inhibitor (NMRA-215) Preclinical Data:

• New positive data from a 12-week diet-induced obesity study in mice demonstrated NMRA-215's class-leading weight loss maintenance potential.
• Although there were unexpected adverse findings in a rat tox study, a repeat study has been initiated, with plans to bring NMRA-215 into the clinic in Q1 2027.

Financial Position:

• Neumora ended 2025 with $182.5 million in cash equivalents and marketable securities, expecting this to support operations into Q3 2027.
• The company's financial foundation remains strong, allowing continued investment in clinical development despite the delayed clinic entry for NMRA-215.

Sentiment Analysis:

Overall Tone: Positive

• Management expressed confidence in 'differentiated profile' and 'best-in-class pharmacology' across pipeline assets. Statements include: 'I am confident in the strength of our science' and 'we are poised to build on the strong momentum from 2025 as we enter a catalyst-rich period'. Positive clinical data highlighted for multiple programs with 'compelling data' and 'encouraging results'.

Q&A:

• Question from Myles Minter (William Blair): Confirmation that one positive KOASTAL-2 or 3 study plus supportive evidence would be sufficient for an MDD filing.
  Response: Management confirmed that one positive study plus supportive data would position them for a pre-NDA meeting with the FDA.

• Question from Brian Abrahams (RBC Capital Markets): Inquiry into the nature of tox study conduct issues for NMRA-215 and FDA historical acceptance of repeated tox studies.
  Response: Management stated findings were procedure-related, a second repeat study is underway, and industry precedent supports progression after a clean repeat study.

• Question from Douglas Tsao (H.C. Wainwright): Request for more detail on what made NMRA-898 the M4 lead and the potential for NMRA-861.
  Response: NMRA-898 was selected as the lead due to its compelling clinical data and profile; NMRA-861 is viewed as viable for future indications.

• Question from Marc Goodman (Leerink): Request for details on the pre-specified analysis for the KOASTAL-2 and KOASTAL-3 readouts.
  Response: Management will report top-line results for each study and analyze the post-pause pooled population to demonstrate patient quality improvements.

• Question from Paul Matteis (Stifel): Request for an update on NMRA-215 maintenance data and the impact of the tox delay on capital allocation.
  Response: Maintenance data was as expected, validating best-in-class potential; the tox delay will free up capital for allocation to other areas.

• Question from Yatin Suneja (Guggenheim): Clarification on whether FDA guidance was sought for the NMRA-215 tox study.
  Response: Management stated they have not discussed the studies with the FDA but repeated the study based on internal and consultant advice, confident it will clear the IND.

• Question from Ami Fadia (Needham & Company): Inquiry into the effect size consistency for NMRA-511 and phase II study design plans.
  Response: Effect size was consistent across time points; management will detail phase II design after the MAD cohort, aiming for a broad label.

• Question from Graig Suvannavejh (Mizuho): Request for differentiation of NMRA-898 versus competitors and thoughts on the muscarinic class.
  Response: Differentiation is based on potent profile, CNS penetration, long half-life, low variability, and strong pharmacodynamic effects, with potential advantages for schizophrenia treatment.

• Question from Myles Minter (William Blair): Follow-up on whether NMRA-898 showed transient blood pressure increases in the SAD study.
  Response: No blood pressure changes were seen in the SAD study; heart rate increases were observed as a pharmacodynamic measure, with future monitoring planned.

• Question from Douglas Tsao (H.C. Wainwright): Inquiry into dosing in the NMRA-215 combination maintenance study and future use cases.
  Response: Combination data validated the hypothesis with consistent weight loss; initial clinical data will focus on monotherapy and combination, with future paradigms to be explored later.

Contradiction Point 1

NMRA-215 Clinical Development Timeline and Funding

Contradiction on when the obesity program will enter Phase I and its funding status.

Paul Matteis (Stifel) - Paul Matteis (Stifel)

2025Q4: The delay in clinical start (now Q1 2027) will free up capital, which can be allocated to other areas. - Joshua Pinto(President)

Can you walk us through the update on NMRA-215's maintenance data and explain how the tox-related delay impacts your capital allocation strategy? - Douglas Dylan Tsao (H.C. Wainwright)

2025Q2: The company is currently planning to advance NMRA-215 through the DIO model and into Phase I on its own, as this progression is funded within the cash runway to 2027. - Joshua Pinto(President)

Contradiction Point 2

Safety Profile and Derisking of M4 PAM Compounds

Contradiction on the type and certainty of preclinical safety data for newer M4 PAMs.

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2025Q4: The repeat 13-week rat tox study has been started... Industry precedent shows that repeated tox studies have allowed programs to progress, and they are confident this will also be the case for NMRA-215. - Nicholas Brandon(CSO)

Would the onus be on us to prove the findings were spurious, and has the FDA historically been okay with progressing a program if a redo of the 13-week tox study comes up clean? - Matthew (on behalf of Paul Matteis, Stifel)

2025Q2: The main derisking step was testing the newer compounds (861 and 898) in rabbits... and no convulsions were observed. This provides confidence in their safety profile. - Nicholas Brandon(CSO)

Contradiction Point 3

KOASTAL Program Confidence and Progress

Contradiction on whether confidence in the KOASTAL studies has changed over time.

Marc Goodman (Leerink) - Marc Goodman (Leerink)

2025Q4: The readout will include top-line results for KOASTAL-2 and KOASTAL-3 individually, plus analyses of the post-pause pooled population... This approach provides a comprehensive view. - Joshua Pinto(President) & Bill Aurora(COO)

Could you provide more details on the pre-specified analysis for the KOASTAL-2 and KOASTAL-3 readouts and what exactly will be presented? - Myles Robert Minter (William Blair)

2025Q2: Confidence in the navacaprant program has not changed since the study design changes were announced. - Daljit Singh Aurora(COO)

Contradiction Point 4

Timing for Clinical Validation of NMRA-215 Combination Weight Loss

Direct contradiction on when the next step for clinical validation (combination study initiation) will occur.

Paul Matteis (Stifel) - Paul Matteis (Stifel)

2025Q4: The delay in clinical start (now Q1 2027) will free up capital, which can be allocated to other areas. - Joshua Pinto(President)

Can you walk us through the update on the maintenance data for NMRA-215 and how the tox-related delay factors into your capital allocation strategy? - Douglas Tsao (H.C. Wainwright)

2025Q1: The changes (SAFER assessment, Verified Clinical Trial screening database) have already benefited enrollment... The exclusion rate is consistent with expectations and does not impact the previously provided timing guidance. - Bill Aurora(COO)

Contradiction Point 5

KOASTAL-2 and KOASTAL-3 Study Timeline

Contradiction on when the studies will resume and be completed.

What are your thoughts on the company's Q4 earnings performance? - Marc Goodman (Leerink)

2025Q4: The readout will include top-line results for KOASTAL-2 and KOASTAL-3 individually, plus analyses of the post-pause pooled population (patients enrolled after protocol amendments in early 2025). This approach provides a comprehensive view... - Joshua Pinto & Bill Aurora(CEO)

Can you provide more details on the pre-specified analysis for the KOASTAL-2 and KOASTAL-3 readouts, including what will be presented and how the results will be interpreted compared to the top-line analysis? - Douglas Tsao (H.C. Wainwright)

2024Q4: They already have a higher proportion of females than males... The studies (K2 and K3) were paused in January 2025 and are guided to resume for another 12-15 months. - Bill Aurora(CEO)