Summary of Neumora Therapeutics 2025 R&D Day Conference Call Company Overview - **Company**: Neumora Therapeutics (NasdaqGS: NMRA) - **Event**: 2025 R&D Day held on October 27, 2025 - **Key Participants**: Paul Burns (CEO), Josh Pinto (President), Nick Brandon (Chief Scientific Officer), Bill Arora (Chief Operating and Development Officer), Dr. Anton P. Porstenson (Alzheimer's expert) Core Industry and Company Insights Alzheimer's Disease and NMRA-511 - **NMRA-511**: A vasopressin 1a receptor antagonist aimed at treating agitation in Alzheimer's disease, which affects over 70% of individuals with Alzheimer's dementia [39][40] - **Unmet Need**: Current treatments have limited efficacy and significant side effects, creating a demand for safer, more effective options [45][62] - **Clinical Evidence**: Preclinical studies indicate that B1A receptor antagonists can reduce agitation symptoms, supported by various studies showing the involvement of the vasopressin system in emotional regulation [40][41] Obesity Treatment and NMRA-215 - **NMRA-215**: A next-generation NLRP3 inhibitor designed for obesity treatment, showing promising weight loss results in preclinical studies [7][13] - **Weight Loss Data**: NMRA-215 demonstrated up to 19% body weight loss as a monotherapy, comparable to leading injectable GLP-1s [14][27] - **Combination Therapy**: When combined with semaglutide, NMRA-215 achieved 26% weight loss, indicating potential for enhanced efficacy in obesity treatment [30][31] Key Data and Findings NMRA-215 Clinical Data - **DIO Models**: NMRA-215 showed dose-dependent weight loss, with significant reductions in food intake and preservation of lean mass compared to semaglutide [15][33] - **Biomarker Improvements**: NMRA-215 also demonstrated positive effects on cardiovascular biomarkers, suggesting additional health benefits beyond weight loss [36] NMRA-511 Clinical Data - **Phase I Study**: NMRA-511 has shown a favorable safety profile in healthy adults and elderly participants, with no serious adverse events reported [42][43] - **Phase Ib Study Design**: The ongoing study aims to assess the efficacy of NMRA-511 in reducing agitation symptoms in Alzheimer's patients, with multiple outcome measures to evaluate its impact [44][72] Strategic Vision and Future Outlook - **Pipeline Potential**: Neumora believes it has assembled an industry-leading pipeline with the potential to deliver significant therapeutic breakthroughs in brain diseases [10] - **Cash Runway**: The company has a cash runway extending into 2027, allowing for continued development and clinical trials across its portfolio [8] - **Upcoming Milestones**: Key data readouts for NMRA-511 and NMRA-215 are expected in the near term, with plans to initiate clinical studies for NMRA-215 in 2026 [9][37] Conclusion - Neumora Therapeutics is positioned to address significant unmet needs in the treatment of Alzheimer's disease and obesity through innovative therapies like NMRA-511 and NMRA-215. The company is focused on advancing its clinical programs while maintaining a strong financial position to support ongoing research and development efforts.

Pipeline Highlights - Neumora is advancing a broad neuroscience pipeline targeting prevalent diseases with novel mechanisms [18] - Multiple catalysts are expected over the next 12 months, including data readouts for Navacaprant and NMRA-511, and advancing NMRA-861 and NMRA-898 to the clinic [20, 21] NMRA-215 (Obesity) - By 2030, 1.13 billion people worldwide are projected to be living with obesity, driving a significant market for obesity treatments estimated at $130-$170 billion [26] - NMRA-215 demonstrated best-in-class monotherapy weight loss of up to 19% in preclinical studies [29, 47] - Combination therapy with NMRA-215 and semaglutide resulted in up to 26% weight loss [30, 50] - NMRA-215 monotherapy matches semaglutide weight loss, while preserving lean mass [56] NMRA-511 (Alzheimer's Disease Agitation) - Approximately 7 million U S adults have Alzheimer's Disease, and this number is expected to increase to 13 million by 2050 [19, 72] - Over 70% of people with Alzheimer's Disease experience agitation at some point [72] - NMRA-511 Phase 1b study data is anticipated around the end of 2025 [66, 142] M4 PAM Franchise (Schizophrenia) - An estimated 3 million patients in the U S have schizophrenia [19, 100] - Neumora has multiple chemically distinct, highly selective M4 muscarinic receptor PAMs, including NMRA-861 and NMRA-898 [99] - NMRA-861 and -898 potentially have more potency than emraclidine across multiple assays [116]

Core Insights - Neumora Therapeutics has initiated a Phase 1 single-ascending dose/multiple-ascending dose study for NMRA-898, a new M4 muscarinic receptor positive allosteric modulator, which is structurally distinct from NMRA-861 [1][2] - The M4 franchise, including NMRA-861 and NMRA-898, aims to provide improved therapeutic profiles for schizophrenia and other neuropsychiatric disorders compared to standard treatments [2][4] - Neumora plans to provide a comprehensive update on its M4 franchise by mid-2026, evaluating the potential advancement of one or both programs based on safety and pharmacokinetic data [2][3] Company Overview - Neumora Therapeutics is a clinical-stage biopharmaceutical company focused on redefining neuroscience drug development with a pipeline of seven programs targeting novel mechanisms for various diseases [6] - The company has licensed intellectual property rights for NMRA-898 from Vanderbilt University, with patent protection extending to 2044 [4] - Neumora's mission is to improve treatment outcomes and quality of life for patients suffering from brain diseases through innovative therapies [6] Industry Context - Schizophrenia affects approximately 3 million adults in the United States, with significant unmet medical needs due to the side effects of current therapies [5] - Current antipsychotics primarily target D2 dopamine receptors, while Neumora's approach focuses on the M4 muscarinic receptor, which may reduce side effects associated with traditional treatments [4][5] - The high discontinuation rate of schizophrenia medications, with about 75% of patients stopping treatment within 18 months, highlights the need for more effective and tolerable options [5]

Core Insights - Neumora Therapeutics announced positive preclinical data for NMRA-215, showing class-leading weight loss of up to 19% as a monotherapy and 26% in combination with semaglutide [1][2] - The company plans to initiate a Phase 1 clinical study for NMRA-215 in the first quarter of 2026 [1][2] Company Overview - Neumora Therapeutics is a clinical-stage biopharmaceutical company focused on redefining neuroscience drug development, with a pipeline of seven programs targeting novel mechanisms for various diseases [5] - NMRA-215 is a highly brain-penetrant, oral NLRP3 inhibitor being developed for obesity treatment, with potential implications for Parkinson's disease as well [4][5] Research and Development - NMRA-215 demonstrated significant weight loss in diet-induced obesity mouse studies, indicating its potential as a next-generation oral treatment for obesity [2][4] - The company emphasizes the potential for NMRA-215 to enable incretin-sparing dosing regimens, enhancing its therapeutic profile [2]

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]

Upgrades - Loop Capital upgraded Union Pacific (UNP) to Hold from Sell with a price target of $227, up from $214, noting that the shares are down 5% year-to-date and valuation multiples are modestly above their five-year ranges [2] - BofA upgraded Prologis (PLD) to Buy from Neutral with a price target of $130, up from $118, highlighting improved conversion rates of new lease proposals into signed leases during Q3 compared to Q2, and an optimistic outlook for demand versus supply dynamics through 2026 [3] - Goldman Sachs upgraded Hershey (HSY) to Buy from Sell with a price target of $222, up from $170, citing a compelling risk/reward scenario following multiple guidance reductions over the past year [4] - Arete upgraded Baidu (BIDU) to Buy from Sell with a price target of $143, emphasizing the potential of Baidu's Kunlun chip venture to offset challenges in its online advertising business due to AI chip shortages in China [5] - Citizens JMP upgraded CoreWeave (CRWV) to Outperform from Market Perform with a price target of $180, projecting significant growth for its graphics processing unit-as-a-service business from $3B-$4B to an estimated $300B [4] Downgrades - TD Cowen downgraded Warner Bros. Discovery (WBD) to Hold from Buy with an unchanged price target of $14, expressing concerns about the stock's risk/reward profile following a recent rally and potential bid from Paramount Skydance [6] - Rothschild & Co Redburn downgraded Live Nation (LYV) to Neutral from Buy with a price target of $170, up from $144, indicating that margin expansion will slow from fiscal 2026, limiting upside potential to earnings estimates [6] - Stifel downgraded VF Corp. (VFC) to Hold from Buy with a price target of $16, up from $15, stating that the stock's risk-reward is now balanced after a 12.5% one-month return, despite a strong outcome from the $600M sale of Dickies [6] - JPMorgan downgraded Camp4 Therapeutics (CAMP) to Neutral from Overweight without a price target, noting that while the company has a cash runway into 2027, its lead program is in the early stages [6] - JPMorgan downgraded Neumora Therapeutics (NMRA) to Underweight from Neutral without a price target, citing a failed Phase 3 trial for its navacaprant treatment in major depressive disorder [6]

Upgrades - Loop Capital upgraded Union Pacific (UNP) to Hold from Sell with a price target of $227, increased from $214, noting shares are down 5% year-to-date and valuation multiples are modestly above five-year lows [2] - BofA upgraded Prologis (PLD) to Buy from Neutral with a price target of $130, up from $118, citing improved lease conversion rates in Q3 compared to Q2 and positive demand-supply dynamics expected through 2026 [3] - Goldman Sachs upgraded Hershey (HSY) to Buy from Sell with a price target of $222, raised from $170, highlighting a compelling risk/reward scenario after multiple guidance reductions [4] - Arete upgraded Baidu (BIDU) to Buy from Sell with a price target of $143, emphasizing the potential of Baidu's Kunlun chip venture to offset challenges in its online advertising business [5] - Citizens JMP upgraded CoreWeave (CRWV) to Outperform from Market Perform with a price target of $180, projecting growth of its GPU-as-a-service business to an estimated $300 billion from $3 billion to $4 billion currently [4] Downgrades - TD Cowen downgraded Warner Bros. Discovery (WBD) to Hold from Buy with an unchanged price target of $14, expressing concerns about the stock's risk/reward after a recent rally [6] - Rothschild & Co Redburn downgraded Live Nation (LYV) to Neutral from Buy with a price target of $170, up from $144, indicating slower margin expansion and reduced earnings upside potential [6] - Stifel downgraded VF Corp. (VFC) to Hold from Buy with a price target of $16, increased from $15, stating that the stock's risk-reward is now balanced after a 12.5% one-month return [6] - JPMorgan downgraded Camp4 Therapeutics (CAMP) to Neutral from Overweight without a price target, noting early-stage challenges in its lead program despite a cash runway into 2027 [6] - JPMorgan downgraded Neumora Therapeutics (NMRA) to Underweight from Neutral without a price target, citing a failed Phase 3 trial for its treatment in major depressive disorder [6]

Summary of Neumora Therapeutics FY Conference Call Company Overview - **Company**: Neumora Therapeutics (NasdaqGS: NMRA) - **Date of Conference**: September 09, 2025 Key Points on NLRP3 Inhibitor Program in Obesity - **Interest in NLRP3 Inhibitor**: The NLRP3 inhibitor program has garnered significant attention due to the success of GLP-1 therapies, which have established a multibillion-dollar market. The competition in the obesity treatment space is intensifying with various mechanisms being explored [2][3] - **Mechanism of Action**: The NLRP3 mechanism operates through CNS-mediated effects, specifically targeting the hypothalamus to reduce appetite. This mechanism is expected to complement existing therapies like incretins and amylins [4][5] - **Potential Advantages**: The NLRP3 inhibitor is anticipated to offer a convenient oral administration option with a low cost of goods, making it more accessible compared to injectable alternatives. It is expected to demonstrate significant weight loss efficacy with improved tolerability [5][6] - **Clinical Data Timeline**: The company plans to release data from the DIO (Diet-Induced Obesity) model later in the year, which will provide insights into the weight loss potential of the NLRP3 inhibitor [6][18] Clinical Paradigms and Development Strategy - **Three Clinical Paradigms**: The company is focusing on three paradigms: monotherapy, combination therapy with GLP-1s, and maintenance therapy after achieving weight loss [9][10] - **Monotherapy Goals**: The aim is to achieve weight loss comparable to existing therapies like semaglutide without the gastrointestinal side effects commonly associated with incretin therapies [10][11] - **Combination Therapy**: The potential to enhance weight loss by combining NLRP3 inhibitors with GLP-1s while reducing the dosage of GLP-1s to minimize side effects is being explored [10][11] - **Long-term Maintenance**: The company is investigating whether patients can maintain weight loss after switching from GLP-1s to NLRP3 inhibitors [11][12] Broader Implications and Future Directions - **Potential Beyond Obesity**: The NLRP3 mechanism may have applications in other metabolic conditions, including cardiovascular protection and osteoarthritis, which could enhance its therapeutic profile [21][22] - **Lean Muscle Mass Preservation**: The NLRP3 inhibitor may also help in preserving lean muscle mass, addressing a common concern with current obesity treatments [24] M4 Program and Other Assets - **M4 PAMs Development**: The company is advancing two M4 positive allosteric modulators (PAMs) with optimized properties for treating conditions like acute schizophrenia and potentially other neuropsych conditions [30][36] - **Focus on Quality**: The company has refined its clinical trial processes to ensure high-quality patient enrollment, particularly for the coastal studies, to improve the chances of success [43][44] - **Upcoming Data**: Phase 1b data for the M4 PAMs and other assets, including five eleven for Alzheimer's disease agitation, is expected by the end of the year [48][49] Conclusion - **Future Outlook**: Neumora Therapeutics is positioned to make significant advancements in obesity treatment with its NLRP3 inhibitor and is also exploring broader applications for its M4 PAMs. The next six months are expected to be critical for the company as it releases key clinical data and refines its development strategies [50]

Core Insights - Neumora Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for brain diseases through novel mechanisms of action [3] Company Participation in Conferences - The company will participate in three investor conferences in September 2025, including one-on-one meetings and a fireside chat [4] - Specific conferences include the Wells Fargo Healthcare Conference on September 4, the Morgan Stanley Annual Global Healthcare Conference on September 8, and the H.C. Wainwright Annual Global Investment Conference on September 9 [4] Therapeutic Pipeline - Neumora's pipeline consists of seven programs targeting a range of underserved and prevalent diseases [3] - The company's mission is to redefine neuroscience drug development to improve treatment outcomes and quality of life for patients [3]

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]