Neumora Therapeutics Conference Call Summary Company Overview - **Company**: Neumora Therapeutics (NasdaqGS: NMRA) - **Event**: 2025 Conference on November 12, 2025 - **Key Speakers**: Josh Pinto (President), Helen Rubinstein (Head of IR) Key Points Clinical Programs and Pipeline - Neumora has six clinical readouts planned across four main clinical stage assets over the next 12 months [2][5] - **NMRA-215**: An NLRP3 inhibitor showing class-leading weight loss data in diet-induced obesity models, with plans to move into human clinical trials in Q1 2026 and deliver proof-of-concept data by the end of 2026 [2][3] - **NMRA-511**: A phase 1b study for Alzheimer's disease agitation is ongoing, with readout expected by the end of 2025. The study is randomized, double-blind, and placebo-controlled, focusing on agitation levels [3][18] - **M4 PAM Franchise**: Two molecules, NMRA-898 and NMRA-861, are in clinical trials, with updates expected by mid-2026 [4][33] - **Navacaprant**: A selective kappa opioid receptor antagonist, with COASTAL 2 and 3 studies on track for readouts in Q1 and Q2 2026 [5] Financial Position - Neumora ended Q3 with over $170 million on the balance sheet, providing a cash runway into 2027 to fund operational plans and clinical catalysts [5] NLRP3 Inhibitor Insights - High correlation (up to 0.9) between diet-induced obesity models and clinical weight loss supports confidence in NMRA-215's potential [6][14] - NMRA-215 achieved IC90 concentrations in the CNS, which is critical for unlocking weight loss potential, unlike other NLRP3 inhibitors [8][11] V1aR Program - The vasopressin system is linked to stress response and agitation, with NMRA-511 showing promise in reducing agitation in Alzheimer's patients [16][17] - The ongoing study includes multiple endpoints to assess the impact on patient agitation and caregiver experience [20] M4 PAM Differentiation - Neumora believes that targeting the M4 receptor through a PAM approach can reduce adverse effects compared to selective agonists [32] - NMRA-898 and NMRA-861 are designed for high CNS penetration, addressing limitations seen in first-generation M4 PAMs [33][36] Strategic Outlook - Neumora aims to position itself as a significant neuroscience company by the end of 2026, with a focus on delivering high-quality data from its clinical programs [46] Additional Considerations - The company is open to various strategic paths for its programs, including collaborations or out-licensing, depending on the data outcomes [29] - Emphasis on the importance of CNS penetration and pharmacology in the development of its compounds [36][41] Conclusion Neumora Therapeutics is at a pivotal stage with multiple clinical programs advancing, a strong financial position, and a clear strategy to leverage its innovative pipeline in neuroscience. The upcoming clinical readouts will be critical in determining the future direction of the company and its assets.

Neumora Therapeutics Conference Call Summary Company Overview - **Company**: Neumora Therapeutics (NasdaqGS: NMRA) - **Event**: FY Conference on November 10, 2025 Key Updates and Core Points NMRA-215 Development - Neumora has completed DIO studies for NMRA-215, an NLRP3 inhibitor targeting obesity, showing class-leading weight loss of 15%-19% in monotherapy settings, comparable to semaglutide [2][7] - NMRA-215 demonstrated up to 26% weight loss when combined with semaglutide, indicating potential for enhanced efficacy through combination therapy [8] - The company plans to initiate first-in-human studies in Q1 2026, with 12-week proof-of-concept data expected by the end of 2026 [3][5] Other Clinical Programs - NMRA-511, a V1A receptor antagonist for Alzheimer's disease agitation, is currently in a phase 1B study, with data expected by year-end [3][21] - Two M4 PAM programs, NMRA-898 and NMRA-861, have entered clinical trials, with updates anticipated by mid-2026 [4][30] Financial Position - As of Q3 2025, Neumora has approximately $170 million in cash, providing a runway into 2027 to fund ongoing clinical trials [5] Pharmacological Insights - Neumora emphasizes the translatability of DIO model data to clinical outcomes, citing a correlation coefficient above 0.9 for weight loss predictions [6] - The company believes its CNS-penetrant pharmacology for NLRP3 inhibitors is superior to competitors, achieving necessary IC90 concentrations in the brain for effective weight loss [12][13] Safety and Patient Quality Improvements - Neumora has partnered with Massachusetts General Hospital to enhance patient selection for clinical trials, aiming to improve the quality of participants in COASTAL studies [35] - The COASTAL II and III studies will have a base size of 332 patients, with potential for a 25% increase based on protocol flexibility [37] Regulatory Considerations - Neumora aims to have two positive studies to support an NDA filing, although one positive study with supportive evidence could also be sufficient [39] Additional Insights - The company is focused on the obesity market as a primary therapeutic area, with plans to explore additional indications based on clinical data outcomes [16][17] - Neumora is preparing to capture biomarker data during its first-in-human studies to inform future development [17] Conclusion - Neumora Therapeutics is positioned for significant clinical milestones in the coming year, with multiple programs advancing through clinical trials and a strong financial foundation to support its initiatives [41]

Core Insights - Neumora Therapeutics announced promising data for NMRA-215, a highly brain-penetrant oral NLRP3 inhibitor, showing class-leading weight loss in diet-induced obesity mouse models, with plans to initiate a Phase 1 study in Q1 2026 [1][4] - The company is advancing Phase 1 studies for two positive allosteric modulators, NMRA-861 and NMRA-898, with a comprehensive update expected by mid-2026 [1][5] - Neumora is on track to report data from a Phase 1b study of NMRA-511 for Alzheimer's disease agitation by the end of 2025 [1][6] - The company has drawn $40 million in non-dilutive capital from K2 HealthVentures, strengthening its financial position [1][3] - As of September 30, 2025, Neumora has $171.5 million in cash, cash equivalents, and marketable securities, expected to support operations into 2027 [1][10] Business Updates - Neumora's CEO highlighted the strength of the pipeline and the differentiated approach to address significant medical challenges, particularly emphasizing the data for NMRA-215 [2] - The company is committed to addressing unmet needs in schizophrenia and neuropsychiatric disorders through the expansion of its M4 muscarinic receptor PAM franchise [2] Financial Performance - For Q3 2025, Neumora reported a net loss of $56.8 million, a decrease from $72.5 million in Q3 2024, attributed to reduced R&D expenses and lower general and administrative costs [10][11] - Research and development expenses for Q3 2025 were $40.5 million, down from $60.6 million in the same period of 2024 [10][11] - General and administrative expenses decreased to $12.2 million in Q3 2025 from $16.0 million in Q3 2024 [10][11]

Core Insights - Neumora Therapeutics, Inc. is hosting a virtual R&D Day on October 27, 2025, to showcase its innovative therapeutic pipeline targeting various diseases [1][4] Group 1: R&D Day Highlights - The R&D Day will feature NMRA-215, a potent NLRP3 inhibitor, with preclinical results from diet-induced obesity mouse models [2] - Upcoming Phase 1b topline data for NMRA-511, a vasopressin 1a receptor antagonist for Alzheimer's agitation, will also be discussed [2] - Additional focus will be on Neumora's M4 franchise, including NMRA-861 and NMRA-898, and navacaprant, a kappa opioid receptor antagonist in Phase 3 studies [2] Group 2: Company Overview - Neumora Therapeutics is a clinical-stage biopharmaceutical company dedicated to addressing significant medical challenges through innovative treatment approaches for brain diseases [4] - The company has a pipeline of seven programs targeting novel mechanisms of action for a range of prevalent diseases [4] - Neumora aims to redefine neuroscience drug development by introducing next-generation therapies that enhance treatment outcomes and patient quality of life [4]

Core Insights - Neumora Therapeutics has initiated a Phase 1 single-ascending dose/multiple-ascending dose study for NMRA-861, with data expected in Q1 2026 [1][4] - The company has prioritized obesity as the lead indication for NMRA-215, a highly brain-penetrant NLRP3 inhibitor, with data from preclinical studies expected in 2025 [1][6][7] - Neumora is entering a catalyst-rich period with up to six clinical data readouts anticipated over the next 18 months, including Phase 3 data for navacaprant in major depressive disorder and Phase 1b data for NMRA-511 in Alzheimer's disease agitation [1][3][8][9] - The company reported a strong financial position with $217.6 million in cash, cash equivalents, and marketable securities, expected to support operations into 2027 [1][14] Pipeline Highlights - NMRA-861, an M4 positive allosteric modulator, has entered Phase 1 clinical studies targeting schizophrenia and other neuropsychiatric disorders [4][5] - NMRA-215 has shown potential for best-in-class brain penetration and is being developed for obesity, with clinical studies expected to start in Q1 2026 [6][7] - Navacaprant is currently in Phase 3 trials for major depressive disorder, with topline data expected in the first half of 2026 [8] - NMRA-511 is on track to report data from a Phase 1b study for Alzheimer's disease agitation by the end of 2025 [9] Financial Overview - For Q2 2025, Neumora reported research and development expenses of $38.7 million, down from $48.6 million in the same period of 2024, primarily due to reduced stock-based compensation and clinical trial costs [14][16] - General and administrative expenses for Q2 2025 were $15.3 million, slightly up from $15.2 million in Q2 2024 [14][16] - The net loss for Q2 2025 was $52.7 million, compared to a net loss of $58.7 million in Q2 2024 [14][16]

Core Viewpoint - Johnson & Johnson (J&J) has decided to discontinue the Phase 3 VENTURA development program for aticaprant as an adjunctive treatment for major depressive disorder (MDD) due to insufficient efficacy in the target patient population, despite the drug being safe and well-tolerated [1][2][3]. Group 1: Development Program and Financial Implications - The decision to halt the VENTURA program is a setback for J&J, which had anticipated annual peak sales of $1-$5 billion from aticaprant in the MDD indication [3]. - J&J is currently conducting full analyses of the VENTURA program data and plans to present findings at a future medical meeting [2]. Group 2: Future Plans and Acquisitions - Despite the setback, J&J maintains its long-term vision to become the 1 neuroscience company by 2030 and expects its Innovative Medicine business to grow at a CAGR of 5% to 7% from 2025 to 2030 [4]. - The company aims to offset the loss from aticaprant with the acquisition of Intra-Cellular Therapies (ITCI) for approximately $14.6 billion, which is expected to be completed later this year [5]. - Upon completion of the acquisition, J&J will gain access to ITCI's marketed drug, Caplyta, which is approved for schizophrenia and bipolar depression, with a regulatory filing submitted for label expansion to include MDD [6]. Group 3: Market Performance - Year to date, J&J's shares have increased nearly 15%, outperforming the industry growth of 12% [7]. Group 4: Industry Context - The setback with aticaprant is not isolated, as Neumora Therapeutics also faced a failure with its lead drug, navacaprant, in a similar MDD study [9]. - Neumora's KOASTAL-1 study did not achieve its primary endpoint, failing to show significant improvement over placebo in alleviating depression symptoms [10].

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]