Financial Data and Key Metrics Changes - The company ended Q2 2025 with $217.6 million in cash, cash equivalents, and marketable securities, which is expected to support operations into 2027 [18] - The total net loss for Q2 2025 was $52.7 million, a decrease from $58.7 million in the same period in 2024, primarily due to reduced stock-based compensation and clinical trial costs [18] Business Line Data and Key Metrics Changes - The company has three clinical stage assets advancing through development, with several near-term catalysts expected [10] - NMRA 215 has been prioritized for obesity treatment, with a focus on its potential as a monotherapy and in combination with GLP-1 therapies [6][10] Market Data and Key Metrics Changes - Obesity currently affects over 2.5 billion people globally, projected to rise to 4 billion by 2035, highlighting a significant market opportunity [7] - A recent study indicated that 68% of individuals on GLP-1s for obesity discontinued use within one year, suggesting a need for better treatment options [8] Company Strategy and Development Direction - The company aims to address large population health challenges by developing better medicines and therapies for prevalent diseases [5] - NMRA 215 is positioned as a potential best-in-class NLRP3 inhibitor targeting obesity, with a focus on central mechanisms of action [41][59] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the pipeline's potential to deliver transformative treatments, with up to six clinical data readouts expected in the next 18 months [9][63] - The company is committed to advancing NMRA 215 through clinical studies, with a focus on its unique approach to obesity treatment [41][60] Other Important Information - The company plans to host an R&D event in Q4 2025 to discuss its programs in more detail [12] - The development strategy includes multiple pathways for success, aiming to deliver breakthrough therapies [12] Q&A Session Summary Question: Can you talk about the preclinical study design in obesity? - The study will assess NMRA 215 as a monotherapy and in combination with semaglutide, focusing on weight loss efficacy and maintenance post-GLP-1 withdrawal [21][23] Question: Can you provide more description on the safety of NMRA 861 compared to the previous molecule? - NMRA 861 is structurally distinct from previous compounds, and preclinical studies have shown no convulsions in rabbits, indicating a safer profile [26][28] Question: Any updates on the COASTal program and enrollment ratios? - Enhanced medical monitoring and verified clinical trials have improved patient enrollment quality, with a higher female enrollment ratio consistent with MDD prevalence [32][34] Question: What are the company's thoughts on the competitive landscape for NMRA 215 in obesity? - The company believes NMRA 215 offers a distinct approach to obesity treatment, leveraging its expertise in developing centrally acting drugs [41][59]

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 - The net loss for the first quarter of 2025 was $68 million, compared to $53.7 million for the same period in 2024 [18] - The company ended the quarter with $249.4 million in cash, cash equivalents, and marketable securities as of March 31, 2025 [18] - The company expects its cash on hand and the $20 million drawn from the K2 facility to support operations into 2027 [19] Business Line Data and Key Metrics Changes - The company is advancing multiple programs towards key milestones, including top-line data for NMRA 511 in Alzheimer's disease agitation expected by the end of the year [7] - The Avacoprant program is progressing with top-line data from COSTAL-three anticipated in Q1 2026 and COSTAL-two in Q2 2026 [7][9] - The M4 PAM franchise is set to bring a best-in-class candidate into the clinic in mid-2025 [14] Market Data and Key Metrics Changes - The company is focused on addressing the global brain disease crisis, which affects over 1.5 billion people [4] - The pipeline includes programs targeting novel mechanisms of action with potential to address prevalent brain diseases [5] Company Strategy and Development Direction - The company aims to revolutionize neuroscience drug development by advancing an industry-leading pipeline of programs [5] - Financial discipline is emphasized as a core tenet of the company's operations, with a focus on maintaining diligent stewardship of capital [8] Management's Comments on Operating Environment and Future Outlook - Management believes they have the right science, people, and strategy to achieve their vision of revolutionizing brain disease treatment [5] - The company is well-positioned to generate value from multiple programs supported by a strong financial foundation [9] Other Important Information - The company has entered into a $125 million debt facility with K2 Health Ventures, with up to $40 million available for draw this year [8] - The intellectual property portfolio supports the pipeline with worldwide rights and patents extending into 2040 [9] Q&A Session Summary Question: Impact of operational changes on enrollment pace for Avacoprant - Management noted that the operational changes have already shown benefits in identifying inappropriate participants, which helps ensure appropriate patients are randomized [21][22] Question: K2 financing details regarding prepayment limitations - Management indicated that the facility allows for flexibility in bringing more capital onto the balance sheet, with the initial $20 million sufficient to extend the cash runway into 2027 [26][28] Question: Patient population tracking for COSTAL program - Management confirmed that they are ensuring proper patient history is assessed for enrollment in K2 and K3, avoiding issues seen in COSTAL-one [33][34] Question: Differentiation of Avacoprant from competitor products - Management expressed confidence in Avacoprant's pharmacology and study design, believing it reflects the most appropriate approach for the mechanism [37][39] Question: Timing for increasing enrollment in COSTAL studies - Management stated that there is flexibility in the enrollment numbers for K2 and K3, with updates to be provided at the appropriate time [53] Question: Comparison of MADRS baseline scores in studies - Management explained that the MADRS scores in K1 are consistent with moderate to severe MDD populations, and the demographic mix in K2 and K3 is more representative historically [57][58]