Neumora Therapeutics, Inc. (NMRA)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 was primarily a financial update and pipeline reset quarter following KOASTAL-1’s negative outcome; management paused KOASTAL-2/-3 to implement stricter medical monitoring (MGH/CTNI SAFER), enhanced screening (VCT database), and concentrated site selection before resuming in March 2025 .
• Guidance shifts: KOASTAL-3 topline now Q1 2026 and KOASTAL-2 Q2 2026 (from H1 2025 previously), NMRA-511 (AD agitation) topline by end-2025 (clarified), next M4 PAM into clinic by mid-2025; bipolar depression Phase 2 discontinued to prioritize KOASTAL .
• Cash, cash equivalents and marketable securities fell to $307.6M; runway maintained into mid-2026, with optionality via debt, BD, ATM, and equity highlighted on the call .
• No product revenue was disclosed; operating lines show net loss of $58.8M and EPS of $(0.37), with sequentially lower R&D vs Q3 due to timing of clinical activities .
• Stock reaction catalysts: timeline deferment to 2026 for KOASTAL-2/-3, trial optimization steps (SAFER/VCT), and confirmation of financing options set the narrative drivers near-term .

What Went Well and What Went Wrong

What Went Well

• Trial optimization plan: added MGH/CTNI SAFER independent diagnostic verification, supplementary VCT screening to exclude professional trial participants, and narrowed to high-experience sites to reduce placebo and ensure eligibility .
• Strengthened liquidity runway: $307.6M in cash, cash equivalents and marketable securities with guidance to fund operations into mid-2026; management reiterated disciplined capital allocation and financing flexibility .
• Clear pipeline milestones: NMRA-511 topline by end-2025; next M4 PAM program to enter clinic by mid-2025; management emphasized confidence in M4 franchise and selective pharmacology .

Quoted management:

• “We are adding the clinician-rated… SAFER approach… to verify the diagnosis and appropriateness of the patient population” .
• “We look forward to reporting top line data from the Phase Ib signal-seeking study by the end of the year” (NMRA-511) .
• “We… progress our next compound into the clinic by mid-2025… well positioned to become a leader in muscarinics” .

What Went Wrong

• KOASTAL-1 miss: navacaprant did not achieve statistical significance on primary or key secondary endpoints; prompted pause and redesign of KOASTAL-2/-3 .
• Timeline slippage: KOASTAL-2/-3 toplines moved from H1 2025 to H1 2026 as studies are optimized and resumed in March 2025 .
• Bipolar depression deprioritized: discontinuation of Phase 2 navacaprant bipolar depression to focus resources on KOASTAL .

Data points and analyst concerns:

• Q4 net loss $(58.8)M and EPS $(0.37); no revenue disclosed, underscoring dependence on clinical milestones and financing .
• Elevated placebo response and gender differential in KOASTAL-1 led to site selection and monitoring changes; concerns about reproducibility and execution in future trials .
• CFO commentary inconsistency: CFO said “Total operating expenses for the fourth quarter were $58.8M,” which matches net loss rather than total operating expenses ($62.9M); investors should rely on the press release tables for precise line items .

Financial Results

Note: Neumora did not disclose revenue for Q2–Q4 2024; margin metrics (gross, EBITDA, net margin) are not applicable without revenue disclosure.

Segment breakdown: Not applicable (development-stage, no reported commercial segments) .

KPIs:

• KOASTAL study target enrollment per study: ~332 patients, with pre-specified ability to increase by up to 25% without protocol amendment ; KOASTAL-2/3 enrolling higher female proportion vs KOASTAL-1 .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “We are adding the clinician-rated Massachusetts General Hospital Clinical Trials Network and Institute SAFER approach… to verify the diagnosis and appropriateness of the patient population” (Aurora) .
• “Sites that participated in other recent positive MDD Phase III studies tended to perform much better… male patients at less-experienced sites had a large placebo effect upwards of 15 points” (Pinto) .
• “We ended the year with $307.6 million… which we expect to support operations into mid-2026” (Milligan) .
• “We have not built an interim analysis into the protocols… given 6-week duration, futility would not yield benefits” (Pinto) .
• “Exposures from KOASTAL-1 were consistent with Phase II; 80 mg achieves ~90% kappa receptor occupancy throughout dosing” (Aurora/Lenz) .

Q&A Highlights

• Medical monitoring and screening overhaul: SAFER independent review added atop existing measures; VCT database complements CTS to exclude professional trial participants .
• Placebo and site effects: Marked male placebo response; sites with recent positive MDD experience performed better; K2/K3 already have higher female proportion .
• Sample size flexibility: Each KOASTAL study can increase enrollment by up to 25% without protocol amendment; powering assumptions unchanged (~90%) .
• Interim analyses: None planned for K2/K3 due to short 6-week study duration; focus on execution quality .
• Pharmacokinetics and dose: KOASTAL-1 exposures consistent with Phase II; 80 mg dose achieves ~90% kappa occupancy; potential to consider higher dose in future given tolerability .
• Financing: Runway mid-2026; open to debt, BD, ATM, equity as needed .

Estimates Context

• Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was unavailable at query time; therefore, comparisons vs consensus cannot be provided. Values retrieved from S&P Global were not accessible due to query limits at the time of analysis.

Where estimates may need to adjust:

• With KOASTAL-2/-3 toplines deferred to H1 2026 and bipolar depression Phase 2 discontinued, models should shift clinical milestone timing and remove bipolar depression value contribution, while incorporating trial optimization measures for probability-of-success assumptions .
• Liquidity preserved into mid-2026; financing scenarios (ATM, BD, debt) may be considered depending on 2025–2026 catalysts .

Key Takeaways for Investors

• The KOASTAL-1 miss catalyzed a comprehensive trial optimization plan (SAFER, VCT, site consolidation) aimed at reducing placebo and improving diagnostic fidelity; toplines deferred to H1 2026 .
• Pipeline remains catalyst-rich in 2025–2026: NMRA-511 topline by end-2025; M4 PAM enters clinic by mid-2025; KOASTAL-2/-3 toplines in 2026 .
• Cash runway into mid-2026 provides time to execute the reset; management highlighted multiple financing levers if needed .
• No revenue reported; operational spending focused on navacaprant Phase 3 program and broader pipeline—Q4 net loss $(58.8)M; EPS $(0.37) .
• Watch for execution signals in 2025: resumption of K2/K3 (March 2025), site quality and medical monitoring updates, and any disclosure on gender differential replication .
• M4 franchise strategy is intact despite competitor challenges; differentiated chemistry and selectivity underpin confidence heading into clinic .
• Near-term trading setups likely hinge on clarity of resumption progress, any interim operational updates on KOASTAL-2/-3, and NMRA-511 enrollment pace; financing commentary suggests optionality without immediate pressure .