Summary of Alto Neuroscience Conference Call Company Overview - **Company**: Alto Neuroscience (NYSE: ANRO) - **Focus**: Development of treatments for treatment-resistant depression (TRD) and cognitive impairment in schizophrenia Key Points on ALTO-207 and TRD - **ALTO-207**: A significant asset for Alto Neuroscience, focusing on TRD, which represents a massive unmet medical need [2][3] - **Dopamine Modulation**: Research indicates that the hypodopaminergic phenotype is prevalent in resistant depression, leading to a focus on dopamine receptor modulation, particularly the D3 receptor [3][4] - **Pramipexole**: A D3-preferring dopamine agonist showing promising efficacy in trials, with a meta-analysis indicating an average effect size of 0.64 across doses [4][6] - **Combination Therapy**: Chase Therapeutics developed a co-formulation of pramipexole and ondansetron to mitigate dose-related nausea and vomiting, allowing for faster and higher dosing [5][6] - **PAX-D Study Results**: A UK-based study showed a Cohen's d effect size of nearly 0.9 at 12 weeks, maintaining efficacy over 48 weeks, indicating strong potential for pramipexole in TRD [6][8] Study Design and Execution - **PAX-D Study Context**: Conducted within the NHS to encourage the use of pramipexole, utilizing a self-report measure (QUIDS) for depression [8][9] - **Retention and Rigor**: The study was well-run with robust results across multiple sites, addressing potential biases in patient selection [9][11] - **Phase 2b and Phase 3 Plans**: Phase 2b is set to start in the first half of 2027, with a sample size of 178 and a treatment duration of 8 weeks [18][19] Intellectual Property and Market Position - **IP Strategy**: Alto has secured intellectual property around the combination therapy and a modified release formulation, enhancing its market position [16][17] - **Non-obviousness Argument**: The combination of pramipexole and ondansetron was not previously explored, supporting the uniqueness of the approach [16] Cognitive Impairment in Schizophrenia - **CIAS Program**: Focuses on cognitive impairment in schizophrenia, a significant unmet need with no existing treatments [33][34] - **Mechanism of Action**: The drug is a PDE4 inhibitor targeting cyclic AMP, which is crucial for cognitive function [34][35] - **Study Design**: A crossover design assessing EEG changes as a primary outcome, with a focus on processing speed and memory [36][37] Execution and Risk Management - **In-house Operations**: Alto manages its trials internally, allowing for greater control and visibility compared to using a CRO [27][25] - **Patient Selection**: Implemented rigorous eligibility criteria to ensure a compliant patient population, reducing the risk of professional patients skewing results [24][25] Future Outlook - **Upcoming Data**: Anticipation for data from the CIAS study and ALTO-100 in the second half of the year [48][49] - **Cash Runway**: The company has sufficient cash to operate through 2029, indicating financial stability for ongoing projects [52] Conclusion - Alto Neuroscience is positioned to address significant gaps in the treatment of TRD and cognitive impairment in schizophrenia, with promising data and a robust pipeline supporting its strategic direction.

Core Insights - Alto Neuroscience, Inc. is a clinical-stage biopharmaceutical company focused on developing precision medicines for neuropsychiatric disorders, aiming to address unmet needs in mental health treatment through innovative therapies [1][6] - The company recently secured approximately $120 million through private placement financing, which is expected to support the advancement of its treatment pipeline for neuropsychiatric conditions [2][6] - Jefferies analyst Andrew Tsai set a price target of $35 for ANRO, indicating a potential upside of 41.24% from its current trading price [1][6] Financial Performance - ANRO's stock is currently priced at $24.43, reflecting a notable increase of 9.75% with a change of $2.17, reaching a year-high of $24.94 [3][6] - The stock's market capitalization stands at approximately $759 million, with a trading volume of 512,010 shares, indicating active investor engagement [4] - The lowest stock price over the past year was $1.60, showcasing significant growth for the company [5]

Core Viewpoint - Jefferies has upgraded Alto Neuroscience to a "Buy" recommendation, reflecting positive market sentiment following a significant financing milestone and the stock's price increase [1][5]. Company Overview - Alto Neuroscience is a clinical-stage biopharmaceutical company focused on developing precision medicines for neuropsychiatric disorders [1][5]. - The company has achieved a market capitalization of approximately $770.45 million, indicating its notable presence in the biopharmaceutical industry [4]. Financial Milestone - Alto Neuroscience secured approximately $120 million through private placement financing, which will support the advancement of its pipeline of precision medicines [2][5]. - This financial backing is crucial for clinical-stage companies, enabling continued research and development activities [2]. Stock Performance - The stock price of Alto Neuroscience (ANRO) is currently at $24.80, reflecting an increase of $2.54, or 11.41% [3][5]. - The stock has fluctuated between a low of $21.76 and a high of $24.94 on the day of the announcement, with $24.94 being its highest price over the past year [3]. - The trading volume of 443,423 shares suggests active investor interest in the stock [4].

MOUNTAIN VIEW, Calif .-- (BUSINESS WIRE) ---- $anro #cns--Alto Neuroscience, Inc. ("Alto†) (NYSE: ANRO), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, announced today that it has entered into a securities purchase agreement with institutional and accredited investors to sell securities in a private placement financing (the "PIPE†) for gross proceeds of approximately $120 million, before deducting offering expenses. The ...

NYSE: ANRO March 2026 1 Disclaimer No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not indepe ...

Financial Performance - The company incurred net losses of approximately $63.2 million and $61.4 million for the years ended December 31, 2025, and 2024, respectively, with an accumulated deficit of approximately $201.6 million as of December 31, 2025[277]. - The company anticipates incurring substantial and increasing losses for the foreseeable future as it continues to develop its product candidates[276]. - The company will require substantial additional financing to achieve its goals, and failure to obtain capital could delay or terminate product development efforts[281]. - The company has reported a milestone payment of approximately $0.8 million to MedRx and issued 46,875 shares of common stock as part of its obligations[287]. - The company’s financial position may be adversely affected by the need to issue equity or incur debt to meet payment obligations[288]. - The Amended Loan Agreement allows for term loans up to $75 million, with $20 million already funded, impacting financial flexibility[373]. - The Convertible Grant Agreement with Wellcome provides for up to $11.7 million, with $2 million drawn down as of December 31, 2025, to advance development of ALTO-100[374]. Product Development and Regulatory Approval - The company has no products approved for commercial sale and has not generated any revenue from product sales to date, indicating a reliance on future regulatory approvals for profitability[278]. - The company expects expenses to increase significantly as it conducts further clinical trials for multiple product candidates, including ALTO-207, ALTO-100, ALTO-300, ALTO-101, ALTO-203, and ALTO-202[277]. - The company is currently conducting Phase 2b clinical trials for ALTO-100 and ALTO-300, and a Phase 2 clinical trial for ALTO-101, which involve subjective assessments that may increase uncertainty in clinical outcomes[298]. - The company plans to seek FDA approval for ALTO-207 through the Section 505(b)(2) regulatory pathway, which could expedite the development process if successful[300]. - The company may need to raise additional funds through collaborations or licenses, which could dilute shareholder value and affect future revenue streams[284]. - The marketing approval process for product candidates is expensive, time-consuming, and uncertain, with no guarantee of success, as many drugs in development fail to complete the approval process[331]. - The company anticipates that ALTO-101, a drug/device combination product, may experience additional delays due to regulatory complexities[327]. - The company faces risks related to lengthy and expensive clinical trials, with a high rate of failure for product candidates in development[289]. Competition and Market Risks - The company faces risks related to competition, including the potential for competitors to develop more effective or safer products[273]. - The company’s ability to commercialize its product candidates will depend on achieving regulatory approvals and establishing adequate reimbursement levels from insurers[279]. - The company faces intense competition from established biopharmaceutical firms and emerging technologies in the neuropsychiatry space[377]. - Key competitive factors for product candidates include efficacy, safety, convenience, price, and reimbursement availability, which will affect market success[378]. - The likelihood of approval for drugs in psychiatry and neurology is historically low at 7.3% and 6.2%, respectively, indicating significant challenges in drug development[363]. Clinical Trials and Patient Recruitment - Patient enrollment in clinical trials is critical, and difficulties in recruiting eligible patients could lead to significant delays or abandonment of trials[303]. - The company may experience delays in clinical trials due to regulatory requirements, site agreements, and participant recruitment challenges[293]. - Delays in clinical testing or marketing approvals could significantly increase product development costs and shorten exclusive commercialization rights, potentially allowing competitors to enter the market first[299]. - The company acknowledges the substantial resources required for research programs, which may not yield viable product candidates due to various challenges[341]. Intellectual Property and Licensing - The company relies on a combination of patents and trade secrets for intellectual property protection, which is crucial for maintaining a competitive edge[415]. - There is no assurance that pending patent applications will result in issued patents that provide sufficient protection against competitors[416]. - The company may struggle to acquire necessary third-party patents, which could hinder its ability to develop and commercialize product candidates[427]. - The company relies on licenses from third parties, including Sanofi and MedRx, for critical intellectual property related to the development of ALTO-101 and other product candidates[432]. - The rights under the Stanford Licensed Patents are exclusive until December 2029, after which they will become non-exclusive, potentially affecting future commercialization efforts[432]. - The company may face significant obligations under existing and future license agreements, including development, commercialization, and royalty obligations, which could impact financial performance[433]. Cybersecurity and Operational Risks - The company is vulnerable to cyberattacks and data breaches, which could adversely affect its operations and reputation[396]. - The company faces significant risks from cyber-attacks, which could lead to operational disruptions, data loss, and increased expenses for recovery[399]. - The reliance on third-party service providers for sensitive information processing poses cybersecurity risks, as these providers may not have adequate security measures[404]. - The company has not experienced significant system failures or breaches to date, but acknowledges the evolving nature of cyber threats and the difficulty in detecting vulnerabilities[403]. Management and Personnel - The company is heavily reliant on its management and clinical personnel, particularly the Founder and CEO, Amit Etkin, and any loss of key personnel could adversely affect product development and commercialization[381]. - The company has executed employment agreements with senior management, but these are terminable at will, posing a risk to retaining key personnel[381]. - As of December 31, 2025, the company had a total of 68 employees and plans to expand its employee base to support growth and operations[379]. Market Access and Reimbursement - Coverage and reimbursement from third-party payors are essential for patient access to the company's products, and failure to secure adequate reimbursement could limit market potential[355]. - The process of obtaining and maintaining reimbursement status is complex and uncertain, with significant variability among different payors[359]. - Companion diagnostic tests may require separate coverage and reimbursement, impacting the prescription rates of the company's product candidates[360]. - International operations face extensive governmental price controls, impacting pricing and reimbursement for product candidates outside the United States[361].

Exhibit 99.1 Alto Neuroscience Reports Full Year 2025 Financial Results and Recent Business Highlights – Acquisition of ALTO-207 targets Treatment-Resistant Depression (TRD) with a clinically-validated mechanism; Phase 2b trial on track to be initiated in the first half of 2026 – – External PAX-D study published in The Lancet Psychiatry demonstrated a 0.87 effect size for the core mechanism of ALTO-207; this effect represents a significantly larger effect size than current standard-of-care treatments – – AL ...

Core Insights - Alto Neuroscience has reported strong financial results for the year 2025, with a cash balance of approximately $177 million, expected to fund operations into 2028 and support four key data readouts in its precision psychiatry pipeline [1][6][9] Business Highlights - The acquisition of ALTO-207, targeting Treatment-Resistant Depression (TRD), is a significant development, with a Phase 2b trial set to begin in the first half of 2026 [1][3] - The PAX-D study published in The Lancet Psychiatry showed a 0.87 effect size for ALTO-207's core mechanism, indicating a significantly larger effect than current standard treatments [1][4] - ALTO-101 has received FDA Fast Track Designation for Cognitive Impairment Associated with Schizophrenia (CIAS), with topline Phase 2 Proof-of-Concept data expected by the end of Q1 2026 [1][5] Financial Performance - Research and development expenses for 2025 were $45.6 million, a decrease from $47.0 million in 2024, primarily due to the completion of previous studies [8] - General and administrative expenses were $20.7 million in 2025, down from $21.6 million in 2024 [9] - The net loss for 2025 was $63.2 million, compared to a net loss of $61.4 million in 2024, with a net loss per share of $2.19 [9][15] Upcoming Milestones - The Phase 2b trial for ALTO-207 is expected to initiate in the first half of 2026, with topline data anticipated in the second half of 2027 [3][6] - ALTO-300 and ALTO-100 are also in ongoing Phase 2b trials, with topline data expected in mid-2026 and the second half of 2026, respectively [7]

Core Viewpoint - Alto Neuroscience is actively participating in various investor conferences and has announced the completion of patient enrollment in a Phase 2 clinical trial for its drug candidate ALTO-101, aimed at treating cognitive impairment associated with schizophrenia [1][1][1] Group 1: Company Announcements - Alto Neuroscience will participate in the Stifel 2026 Virtual CNS Forum on March 17, 2026, with a live webcast available for investors [1] - The company is also set to participate in the TD Cowen 46th Annual Healthcare Conference from March 2-5, 2026, with a presentation scheduled for March 3, 2026, at 1:50 PM ET [1] Group 2: Clinical Development - Alto Neuroscience has completed patient enrollment in its Phase 2 proof-of-concept clinical trial for ALTO-101, a transdermal phosphodiesterase-4 (PDE4) inhibitor targeting cognitive impairment associated with schizophrenia [1] Group 3: Research Contributions - A review co-authored by Alto Neuroscience's leadership team has been published in the American Journal of Psychiatry, discussing neuroplasticity as a core driver of psychiatric diseases and potential treatments [1]

Summary of Alto Neuroscience Conference Call Company Overview - **Company**: Alto Neuroscience - **Industry**: Biotechnology, specifically focused on mental health care and psychiatric treatments Core Programs and Focus Areas - **Mission**: Transform mental health care through precision psychiatry, targeting unmet needs in depression and schizophrenia [3][4] - **Key Programs**: - **ALTO-207**: A fixed-dose combination of pramipexole (dopamine agonist) and ondansetron (antiemetic), currently in Phase IIb, with plans for Phase III next year [4][6] - **ALTO-101**: Targets cognitive impairment in schizophrenia, with no current approved treatments available [12][13] - **ALTO-300**: An adjunctive treatment for depression using agomelatine, with Phase IIb results expected this year [4][49] ALTO-207 Highlights - **Mechanism**: Combines pramipexole, which is effective for treatment-resistant depression (TRD), with ondansetron to mitigate side effects [6][8] - **Clinical Data**: The PAXD study showed a Cohen's d of almost 0.9, indicating significant efficacy in TRD patients [7] - **Safety and Tolerability**: 20% of patients discontinued due to nausea, highlighting the need for improved tolerability [8][26] - **Commercial Strategy**: Aiming to position ALTO-207 as a widely used adjunctive treatment, potentially expanding to monotherapy in the future [25][26] ALTO-101 Highlights - **Target**: Cognitive impairment in schizophrenia, a significant unmet need affecting 0.5%-1% of the global population [12][13] - **Mechanism**: Utilizes a PDE4 inhibitor to enhance neuroplasticity and cognition [13][14] - **Trial Design**: A crossover design with EEG as the primary outcome, focusing on circuit engagement and cognitive improvement [14][45] ALTO-300 Highlights - **Mechanism**: Agomelatine acts as a melatonergic agonist and 5-HT2C antagonist, differing from traditional antidepressants [49] - **Biomarker Use**: Employs an EEG biomarker for patient selection, aiming to enhance treatment efficacy [50] Key Insights and Future Directions - **Patient Selection**: Emphasis on biomarker-defined populations to improve trial outcomes and treatment efficacy [18][20] - **Regulatory Strategy**: Plans for a 505(b)(2) submission strategy, leveraging existing data for faster approval [12][43] - **Intellectual Property**: Strong IP portfolio extending into the mid-2040s, covering co-formulations and treatment methods [43] Additional Considerations - **Real-World Data**: Challenges in achieving effective dosing of pramipexole in clinical practice, with many patients unable to reach effective doses [27][28] - **Innovative EEG Use**: Potential for at-home EEG monitoring to facilitate patient selection and treatment monitoring [52] This summary encapsulates the key points discussed during the conference call, focusing on the company's strategic direction, product pipeline, and the innovative approaches being taken to address significant mental health challenges.