Financial Data and Key Metrics Changes - The net loss for Q1 2025 was $68 million, compared to $53.7 million for the same period in 2024 [20] - The company ended the quarter with $249.4 million in cash, cash equivalents, and marketable securities as of March 31, 2025 [20] Business Line Data and Key Metrics Changes - The company is advancing multiple programs towards key milestones, including NMRA511 for Alzheimer's disease agitation and Avacoprant in the phase three COASTal program for major depressive disorder (MDD) [9][10] - The company expects to deliver top-line data for NMRA511 by the end of 2025 and for the COASTal studies in early to mid-2026 [9][10] Market Data and Key Metrics Changes - The company has entered into a $125 million debt facility with K2 Health Ventures, with $40 million available for draw this year, which strengthens its financial position [10][11] - The company expects its cash and the K2 facility to support operations into 2027, well beyond anticipated clinical data milestones [11] Company Strategy and Development Direction - The company aims to address the global brain disease crisis, which affects over 1.5 billion people, by advancing an industry-leading pipeline targeting novel mechanisms of action [6][7] - The company is focused on clinical execution and maintaining financial discipline to support its pipeline and achieve value-creating milestones [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their pipeline to revolutionize the treatment of brain diseases and emphasized the importance of addressing unmet medical needs [6][7] - The management highlighted the strong intellectual property portfolio supporting their programs, with patents extending into 2040 [11] Other Important Information - The company is implementing operational changes to improve patient enrollment in clinical trials, ensuring appropriate patient selection [12][14] - The company is focused on enhancing the safety and efficacy of its treatments, particularly in the M4 PAM franchise and NMRA511 for Alzheimer's disease agitation [12][18] Q&A Session Summary Question: Impact of operational changes on enrollment pace - Management noted that operational changes have already shown benefits in identifying appropriate participants for the studies, maintaining confidence in enrollment timelines [24][27] Question: Details on K2 financing and prepayment limitations - The company clarified that the K2 facility extends their cash runway into 2027, with flexibility for additional capital drawdowns as needed [29][31] Question: Patient population tracking in COASTal program - Management confirmed that they are ensuring proper patient history assessments and do not plan for interim analyses in the ongoing studies [38][39] Question: Differentiation of Avacoprant from competitors - Management expressed confidence in Avacoprant's pharmacology and study design, believing it reflects the most appropriate approach for the mechanism [41][43] Question: Timing for increasing enrollment in COASTal studies - Management indicated flexibility in enrollment numbers for COASTal studies and will provide updates as necessary [56] Question: Comparison of MADRS baseline scores in studies - Management confirmed that the patient demographics in K2 and K3 are more representative compared to K1, with a balanced gender distribution [61]

Financial Data and Key Metrics Changes - Total operating expenses for Q4 2024 were $58.8 million, down from $108.7 million in Q4 2023, while full-year operating expenses increased slightly to $243.8 million from $235.9 million in 2023 [32] - As of December 31, 2024, the company had $307.6 million in cash, cash equivalents, and marketable securities, expected to support operations into mid-2026 [33] Business Line Data and Key Metrics Changes - The company is advancing navacaprant, currently in Phase 3 development for MDD, and has made changes to optimize ongoing studies based on learnings from the KOASTAL-1 study [11][12] - NMRA-511 is being investigated in a Phase 1b study for Alzheimer's disease agitation, with top-line data expected by the end of 2025 [15][17] Market Data and Key Metrics Changes - Approximately 70% of the estimated 7 million people living with Alzheimer's disease experience agitation, indicating a significant unmet need in this market [16] Company Strategy and Development Direction - The company aims to deliver transformative medicines for brain diseases, focusing on a pipeline of seven programs targeting novel mechanisms of action [7] - The strategy for the KOASTAL program includes enhancing patient monitoring and site selection to improve study outcomes [25][26] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of navacaprant despite previous study results, citing a strong pipeline and a commitment to addressing unmet needs in brain disease treatment [19][31] - The company is focused on disciplined capital allocation to leverage its strong balance sheet for future catalysts across its programs [32] Other Important Information - The company has discontinued the Phase 2 trial for navacaprant in bipolar depression to prioritize resources for the KOASTAL program [14] - The company is advancing four preclinical programs targeting various brain disorders, including Alzheimer's agitation and schizophrenia [29] Q&A Session Summary Question: Differences between KOASTAL-1 vendor and SAFER - The company is enhancing medical monitoring to confirm patient diagnoses and is partnering with Mass General Hospital's SAFER for independent reviews [37][39] Question: Enrollment status of KOASTAL-2 and 3 - The company is not disclosing specific enrollment numbers but is optimistic about the changes made to improve outcomes in these studies [51] Question: Placebo response in KOASTAL-1 - The company identified that site experience significantly impacted performance, particularly in male patients, and is focusing on site selection for future studies [46][48] Question: Cash runway and financing strategies - The company maintains a strong financial position and is exploring various funding mechanisms to support operations [66][70] Question: Interim analysis for KOASTAL studies - No interim analysis is planned for KOASTAL-2 and 3 due to the short duration of the studies [87] Question: Update on NMRA-266 clinical hold - The company is working to determine the path forward for NMRA-266 while progressing follow-on compounds in the M4 franchise [92]