Summary of Conference Call Company and Industry - The discussion revolves around a company focused on precision psychiatry, particularly in the treatment of psychiatric disorders such as depression, bipolar depression, schizophrenia, and PTSD. The company employs advanced techniques like machine learning and EEG to develop targeted therapies. Core Points and Arguments 1. **Precision Psychiatry Approach**: The company emphasizes a systematic understanding of the biology of individual patients with psychiatric disorders, moving beyond traditional diagnostic methods to identify distinct biological subtypes for targeted drug development [1][2] 2. **Machine Learning and EEG**: Recent data presented at the Society of Biological Psychiatry meeting highlighted the use of machine learning and EEG to predict placebo responses in depression, which has been a significant challenge in differentiating drug effects from placebo effects [4][5][6] 3. **Alto 203 Overview**: Alto 203, a histamine H3 inverse agonist, is designed to increase dopamine levels in the reward system, which is crucial for motivation and mood. The drug has shown potential in increasing positive subjective emotions in healthy individuals [10][11] 4. **Clinical Trial Readouts**: The company is expecting proof of concept data for Alto 203 in Major Depressive Disorder (MDD) this quarter, focusing on pharmacodynamic responses and understanding the drug's effects through various measures [9][12][13] 5. **Alto 101 Development**: Alto 101, a PDE4 inhibitor, aims to enhance neuroplasticity and cognition in schizophrenia. The company has addressed historical tolerability challenges by reformulating the drug into a transdermal patch to reduce adverse events [14][20] 6. **Cognitive Impairment in Schizophrenia**: The company identifies a significant unmet need in treating cognitive impairment associated with schizophrenia, which often precedes psychotic symptoms. There are few existing treatments, creating a substantial opportunity for new therapies [22][25] 7. **Learnings from ALTO 100 Trial**: The company learned from the ALTO 100 trial that compliance issues significantly impacted results. Adjustments have been made to recruitment strategies to ensure better patient selection and adherence in future studies [31][32][34] 8. **Market Landscape**: The current landscape for psychiatric treatments is described as open, with a high demand for effective therapies. The company aims to leverage its precision psychiatry approach to fill this gap [39][40] Other Important Content - **Biomarker Strategy**: The company is focused on developing robust and reproducible biomarkers to guide treatment selection and improve the chances of successful outcomes in clinical trials [36][38] - **Regulatory and Safety Considerations**: The company is aware of historical safety concerns with certain drugs and is taking steps to ensure that the new formulations are well tolerated and safe for patients [35] - **Future Outlook**: The company is optimistic about upcoming clinical trial readouts and the potential for its precision psychiatry approach to make significant advancements in the treatment of psychiatric disorders [40]

Financial Performance - For the years ended December 31, 2024, and 2023, the company's net losses were approximately $61.4 million and $36.3 million, respectively, with an accumulated deficit of approximately $138.4 million as of December 31, 2024[226]. - The company has incurred substantial losses since its inception and does not expect to generate significant revenue until regulatory approval and successful commercialization of its product candidates[227]. - The company anticipates incurring substantial and increasing losses for the foreseeable future as it continues to develop its product candidates[225]. - The company expects to incur significant expenses related to clinical trials, regulatory approvals, and commercialization efforts for its product candidates[230]. - The company has invested heavily in its product candidates and plans to continue significant investments, although it does not expect to generate revenue for many years[305]. Cash and Funding - The company had $168.7 million in cash, cash equivalents, and restricted cash as of December 31, 2024, which is expected to fund operations for at least the next 12 months[231]. - The company requires substantial additional capital to achieve its business objectives, with potential market volatility impacting access to funds[234]. - The company may need to finance cash needs through equity offerings, debt financings, or collaborations, which could dilute ownership interests[234]. - The company has entered into an Amended Loan Agreement providing for term loans of up to $75 million, with $20 million funded in January 2025, and additional amounts available subject to achieving certain milestones[312]. - A Convertible Grant Agreement with The Wellcome Trust Limited provides for an unsecured convertible loan of up to approximately $11.7 million, aimed at advancing the development of ALTO-100 in bipolar depression[313]. Product Development and Clinical Trials - The company has no products approved for commercial sale and has not generated any revenue from product sales to date[227]. - The company faces high risks in product candidate development, with a lengthy and expensive process and uncertain outcomes[239]. - The FDA has not affirmatively adopted the company's unique approach to identifying biomarkers, which may lead to delays in clinical trials[240]. - The company may experience delays in clinical trials due to various factors, including regulatory requirements and participant recruitment challenges[243]. - A partial clinical hold was recently resolved by amending the dosing paradigm for ALTO-101 in an ongoing Phase 2 trial[245]. - The ongoing Phase 2b clinical trials of ALTO-100 in patients with bipolar depression and ALTO-300, as well as Phase 2 clinical trials of ALTO-101 and ALTO-203, involve subjective assessments which may increase uncertainty in clinical trial outcomes[249]. - Delays in clinical testing or marketing approvals could significantly increase product development costs and impair the ability to commercialize product candidates[250]. - Patient enrollment challenges may lead to delays in clinical trials, affecting the overall timeline and success of product development[251]. - The company plans to focus development activities on patients characterized by specific biomarkers, which may narrow potential patient populations and complicate enrollment[252]. - Adverse side effects or unexpected characteristics observed in clinical trials could lead to interruptions or halts in development, impacting market acceptance[258]. - The company anticipates needing to develop companion diagnostics for certain therapeutic product candidates, which is a time-consuming and costly process[263]. - Regulatory complexities surrounding companion diagnostics may limit the marketing of approved products to specific patient populations[264]. - If companion diagnostics are not successfully developed or approved, the company's business and financial condition could be materially harmed[267]. - The company has not yet succeeded in demonstrating efficacy for any product candidates in clinical trials, reporting negative topline results for the Phase 2b trial of ALTO-100 in MDD in October 2024[268]. - The company has never commercialized a product candidate and may experience delays or unexpected difficulties in obtaining regulatory approval for its product candidates[271]. - The company is developing ALTO-300, which is already an approved antidepressant in Europe and Australia, solely in the United States, but potential recalls or safety concerns in other regions could adversely affect its U.S. approval[271]. - The FDA may require additional clinical trials or impose restrictions on the marketing approval of product candidates, which could delay commercialization[276]. - The marketing approval process is expensive, time-consuming, and uncertain, with only a small percentage of drugs in development successfully completing the approval process[275]. - The company may face challenges in identifying appropriate patients for clinical trials, which could adversely affect the development of its product candidates[270]. - Interim and topline data from clinical trials may change as more patient data become available, potentially impacting the company's business prospects[278]. - The company has not received approval to market any product candidates from regulatory authorities in any jurisdiction, and future candidates may also fail to obtain approval[274]. - The company’s ability to develop and commercialize product candidates may be impaired if it fails to replicate positive results from preclinical studies or clinical trials[282]. - The likelihood of approval from Phase 1 in psychiatry and neurology is 7.3% and 6.2%, respectively, indicating significant challenges in drug development in these fields[302]. - The company intends to focus on developing product candidates for specific indications that are most likely to succeed, potentially forgoing other opportunities[286]. - Obtaining regulatory approval in one jurisdiction does not guarantee success in others, and delays in one region may negatively impact approvals elsewhere[288]. - The company has never commercialized a product candidate, and market acceptance among physicians, patients, and payors is uncertain[291]. - The successful commercialization of product candidates will depend on coverage, adequate reimbursement levels, and favorable pricing policies established by governmental authorities and health insurers[294]. - Third-party payors are increasingly challenging prices for biopharmaceutical products, which may limit the company's ability to successfully commercialize its products[296]. - The process of obtaining and maintaining reimbursement status is time-consuming and costly, with no uniform policy among third-party payors in the United States[298]. - International operations are subject to extensive governmental price controls, which may restrict the pricing and usage of the company's products[300]. - The company faces significant uncertainty regarding third-party payor coverage and reimbursement for newly approved products, which varies widely by country[297]. - The development of product candidates for CNS disorders is extremely difficult, relying on subjective patient-reported outcomes, which complicates evaluation[302]. Competition and Market Risks - The company faces intense competition in the biopharmaceutical industry, particularly in the areas of major depressive disorder, bipolar depression, and schizophrenia, from companies with greater financial resources and experience[317]. - The company is dependent on its management and clinical personnel, and any inability to retain or recruit qualified individuals could adversely affect its business[223]. - The company faces intense competition for qualified personnel, particularly in the San Francisco Bay Area, which may impede its ability to achieve development objectives and implement business strategy[324]. - There is a significant risk of employee misconduct, which could lead to noncompliance with regulatory standards and adversely affect the company's financial condition and operations[325]. - Future growth may depend on the company's ability to obtain regulatory approvals in foreign markets, including the EU, UK, and Japan, which involves navigating complex regulatory requirements[326]. Intellectual Property and Legal Risks - The company relies on a combination of patents and trade secrets for intellectual property protection, which may not be sufficient against competitors[352]. - Patent applications may not result in issued patents, and existing patents may not provide adequate protection against infringement[355]. - The company relies on licenses from third parties, such as Sanofi and MedRx, for critical intellectual property related to product candidates like ALTO-101[371]. - The rights under the Stanford Licensed Patents will become non-exclusive after December 2029, which may affect competitive positioning[371]. - The company may face challenges in obtaining exclusive rights to use licensed intellectual property in all relevant fields and territories, potentially impacting future commercialization efforts[369]. - Legal assertions of patent invalidity and unenforceability are unpredictable, and adverse outcomes could significantly impact the company's patent protection and competitive position[362]. - The company may miss opportunities to strengthen its patent position if patentable aspects of inventions are not identified in time[374]. - The licensing and acquisition of third-party intellectual property rights is competitive, and established companies may have advantages that hinder the company's ability to secure necessary rights[367]. - The company may not have control over the preparation, filing, and maintenance of patents licensed from third parties, which could adversely affect its ability to develop and commercialize products[375]. - The company may incur substantial expenses to enforce rights to licensed technology if misuse occurs, impacting financial condition[376]. - Future licensing agreements may be amended in ways that could allow competitors to access intellectual property, potentially harming business prospects[377]. - Disputes over intellectual property rights could narrow the scope of rights or increase financial obligations under licensing agreements, adversely affecting operations[378]. - The company may face significant royalty obligations if infringement of third-party patents is found, impacting profitability[380]. - Limitations on the ability to utilize licensed technologies could delay or prevent new product introductions, affecting business strategy[381]. - The unpredictability of patent protection and potential legal challenges could significantly harm the company's business and financial condition[391]. - The company may not identify relevant third-party patents, increasing the risk of infringement claims that could adversely affect product development[393]. - Numerous U.S. and foreign patents and pending patent applications owned by third parties may interfere with the company's ability to make, use, and sell its product candidates[394]. - The company may face significant costs and time-consuming litigation to protect its intellectual property rights, which could divert management and scientific personnel from their core responsibilities[397]. - The company cannot assure that third-party patents do not exist that might be enforced against its current technology, potentially resulting in significant royalty obligations[396]. - The company may be required to litigate or obtain licenses from third parties to develop or market its product candidates, which could be costly or unavailable on commercially reasonable terms[400]. - The company’s commercial success depends on its ability to develop and market its product candidates without infringing third-party intellectual property rights[401]. - The company may face challenges in proving patent invalidity, as the burden of proof is high in U.S. courts, making it difficult to invalidate existing patents[402]. - The company may choose to challenge the validity of third-party patents through expensive proceedings, which could consume significant resources[404]. - The company’s rights under certain licensed patents may become non-exclusive after specific periods, potentially impacting its competitive position[406]. - The U.S. federal government retains certain rights in inventions produced with its financial assistance, which could affect the company's ability to enforce patents developed with federal funds[407]. - Changes in U.S. patent law, particularly the Leahy-Smith Act, could increase uncertainties and costs in patent prosecution and enforcement, potentially affecting the company's ability to protect its intellectual property[408]. - The transition to a first inventor to file system under the Leahy-Smith Act means that a third party could obtain a patent for an invention even if the company invented it first, necessitating timely patent application filings[410]. - The U.S. Supreme Court's recent rulings have narrowed patent protection scope, which could weaken the company's ability to secure new patents and impact future patent expiration dates[411]. - The introduction of the European Unified Patent Court (UPC) on June 1, 2023, adds uncertainty to European patent litigation, potentially allowing competitors to challenge the company's patents more easily[412]. - The company may face claims regarding inventorship or ownership of patents, which could lead to litigation and the loss of valuable intellectual property rights[413]. - Patent terms are limited to generally 20 years from the earliest filing date, which may not provide sufficient protection against competition from generics or biosimilars once patents expire[417]. - The company may not obtain patent term extensions under the Hatch-Waxman Amendments, which could allow competitors to launch products after patent expiration, adversely affecting business prospects[418]. Cybersecurity and Operational Risks - Cybersecurity threats are prevalent and increasing, posing risks to the company's information technology systems and sensitive data[336]. - The company may face additional cybersecurity risks due to remote work and potential vulnerabilities in acquired entities' systems[341]. - The company has not experienced significant system failures or security breaches to date, but vulnerabilities may exist that could be exploited without detection[342]. - The company relies on third-party service providers for sensitive information processing, which poses risks related to information security and potential adverse consequences from security incidents[343]. - Significant security breaches could lead to material costs and disrupt the company's ability to provide services, including clinical trials[345]. - The company may face insufficient recourse against third-party disruptions, necessitating significant resources to mitigate impacts and develop protections[346]. - Business continuity plans may not adequately protect against natural disasters, which could materially affect operations and financial conditions[349]. Market Projections and External Factors - Market projections for product candidates may be overly optimistic, with actual market sizes potentially being smaller than estimated[350]. - Health pandemics or epidemics could disrupt operations and delay research and development programs, negatively impacting trial activities and timelines[351].

Financial Position - As of December 31, 2024, the company reported cash and cash equivalents of approximately $168 million[9] - The company's financial closing procedures for the year ended December 31, 2024, are not yet complete, and final results may differ materially from preliminary estimates[10] - The preliminary financial data presented is subject to change and should not be relied upon without caution[10] - The independent registered public accounting firm has not audited or reviewed the preliminary financial data[10] Sales Agreement - The company has entered into a Sales Agreement with Leerink Partners LLC to offer and sell shares of its common stock, with an aggregate offering price of up to $75 million[5] - The agent will receive a commission of up to 3.0% on the aggregate gross sales price per share sold under the agreement[6] - The Sales Agreement is incorporated by reference in the company's Registration Statement on Form S-3 filed on February 3, 2025[13] - The ATM Shares will be sold through "at the market offerings" as defined in Rule 415(a)(4) under the Securities Act[7] - The company has no obligation to sell any of the ATM Shares and may suspend or terminate the agreement at any time[7] Company Classification - The company is classified as an emerging growth company under the Securities Act of 1933[4]

Core Viewpoint - Alto Neuroscience, Inc. is under investigation for potential violations of securities laws, prompting affected investors to reach out to the Schall Law Firm for assistance [1] Group 1 - The investigation into Alto Neuroscience, Inc. suggests possible misconduct related to securities regulations [1] - Investors who believe they have been impacted by the company's actions are encouraged to contact legal representation [1]

Core Viewpoint - The Schall Law Firm is inviting shareholders of Alto Neuroscience, Inc. who have experienced losses to participate in an inquiry regarding potential securities fraud [1] Group 1 - The inquiry is focused on allegations of securities fraud involving Alto Neuroscience, Inc. [1] - Shareholders who have incurred losses are encouraged to join the investigation [1] - The law firm aims to determine whether the company engaged in any fraudulent activities that may have affected shareholder value [1]

Alto Neuroscience, Inc. (ANRO) could be a solid addition to your portfolio given its recent upgrade to a Zacks Rank #2 (Buy). This upgrade primarily reflects an upward trend in earnings estimates, which is one of the most powerful forces impacting stock prices.A company's changing earnings picture is at the core of the Zacks rating. The system tracks the Zacks Consensus Estimate -- the consensus measure of EPS estimates from the sell-side analysts covering the stock -- for the current and following years.In ...

Financial Performance - The company reported net losses of $16.8 million and $46.2 million for the three and nine months ended September 30, 2024, respectively, compared to $9.1 million and $25.1 million for the same periods in 2023[142]. - The company has not generated any revenue from product sales and expects to incur significant operating losses and negative cash flows for the foreseeable future[142][144]. - The company anticipates continued net losses and increased operating expenses as it expands its headcount and develops its product candidates[169]. - Net loss for the three months ended September 30, 2024, was $16.8 million, compared to a net loss of $9.1 million for the same period in 2023, indicating an increase of 84%[160]. - Net cash used in operating activities was $34.4 million for the nine months ended September 30, 2024, compared to $21.9 million for the same period in 2023, an increase of 57%[177]. - Net cash used in operating activities was $(34.4) million for the nine months ended September 30, 2024, compared to $(21.9) million for the same period in 2023[184]. Cash and Funding - As of September 30, 2024, the company had an accumulated deficit of $123.2 million and cash, cash equivalents, and restricted cash of $182.2 million[142][147]. - The company has raised approximately $275.6 million from equity financings since its inception in 2019, including $133.0 million from its IPO in February 2024[141][147]. - Cash, cash equivalents, and restricted cash amounted to $182.2 million as of September 30, 2024, compared to $82.5 million as of December 31, 2023[172]. - The company expects existing cash and cash equivalents of $181.7 million to fund operations into 2027, but actual results may vary[185]. - Net cash provided by financing activities was $135.6 million for the nine months ended September 30, 2024, primarily from the issuance of 9,246,000 shares at $16.00 per share[179]. - Material cash requirements as of September 30, 2024, include obligations under a Term Loan and lease commitments totaling $7.1 million over the next five years[188]. - The company entered into a Convertible Grant Agreement with Wellcome for up to approximately $11.7 million, with $1.3 million funded upon execution[192]. Research and Development - The company is currently evaluating ALTO-100 in a Phase 2b study for bipolar depression, with a target enrollment of approximately 200 patients and topline data expected in 2026[137]. - ALTO-300 is being evaluated in a 200-patient Phase 2b trial for major depressive disorder (MDD), with topline data expected in the first half of 2025[138]. - ALTO-203 is in a Phase 2 proof-of-concept trial for MDD, with topline data expected in the first half of 2025[139]. - ALTO-101 is being evaluated in a Phase 2 proof-of-concept trial for cognitive impairment associated with schizophrenia, with topline data expected in the second half of 2025[140]. - The company intends to develop ALTO-202, a novel NMDA receptor antagonist for the treatment of MDD[140]. - Research and development expenses increased to $13.1 million for the three months ended September 30, 2024, up from $8.0 million in the same period of 2023, representing a 64% increase[162]. - Research and development expenses for the nine months ended September 30, 2024, totaled $36.2 million, up from $20.6 million in the same period of 2023, a 75% increase[167]. Operating Expenses - General and administrative expenses rose to $5.8 million for the three months ended September 30, 2024, compared to $1.8 million in the same period of 2023, marking a 228% increase[163]. - General and administrative expenses for the nine months ended September 30, 2024, were $15.4 million, compared to $5.4 million in the same period of 2023, representing a 185% increase[167]. - Total operating expenses for the three months ended September 30, 2024, were $18.9 million, up from $9.7 million in the same period of 2023, reflecting a 95% increase[160]. - Stock-based compensation expenses increased by $3.8 million to $6.1 million for the nine months ended September 30, 2024, compared to $2.3 million for the same period in 2023[182]. Agreements and Milestones - The company achieved a clinical milestone under the Teva Agreement and paid $0.5 million in cash during the nine months ended September 30, 2024[197]. - A milestone under the MedRx Agreement was achieved in April 2024, resulting in a payment of $0.75 million in cash and the issuance of 46,875 shares, recognizing an expense of $1.5 million[199]. - The company has entered into multiple license agreements, including those with Stanford University, Sanofi, and Cerecor, to expand its product development capabilities[193][194][195]. Company Classification and Reporting - The company is classified as an "emerging growth company" under the JOBS Act, allowing it to rely on certain exemptions from public company reporting requirements for up to five years post-IPO[202]. - The company has opted for an extended transition period for complying with new or revised accounting standards, delaying adoption until those standards apply to private companies[203]. - The company will cease to be an "emerging growth company" upon reaching $1.235 billion in annual revenue or other specified conditions[203]. - The company is also classified as a "smaller reporting company," which allows it to utilize scaled disclosures as long as certain revenue and stock valuation thresholds are met[204]. - The voting and non-voting common stock held by non-affiliates must be less than $250 million or annual revenue must be less than $100 million to maintain smaller reporting company status[204]. - The company is not required to provide quantitative and qualitative disclosures about market risk due to its smaller reporting company status[205].

Financial Performance - The company incurred a net loss of $16.8 million for Q3 2024, compared to a net loss of $9.1 million for the same period in 2023[13]. - The net loss for the three months ended September 30, 2024, was $16,783,000, compared to a net loss of $9,141,000 in the same period last year, reflecting an 83.5% increase in losses[18]. - The net loss per share attributable to common stockholders for the three months ended September 30, 2024, was $(0.62), compared to $(2.44) for the same period in 2023[18]. - Other income for the three months ended September 30, 2024, was $2,103,000, compared to $577,000 in the same period last year, showing a 264.5% increase[18]. Research and Development - Research and development expenses for Q3 2024 were $13.1 million, up from $8.0 million in Q3 2023, primarily due to costs associated with ongoing Phase 2b studies[11]. - Research and development expenses for the three months ended September 30, 2024, were $13,060,000, compared to $7,967,000 for the same period in 2023, representing a 64.5% increase[18]. - The company plans to incorporate learnings from the ALTO-100 study into its other ongoing clinical programs[2]. Clinical Trials - Topline data from two major depressive disorder (MDD) trials, ALTO-300 and ALTO-203, are expected in the first half of 2025[1]. - Enrollment for the Phase 2b trial of ALTO-300 is on track, with 200 patients expected to participate, and topline data anticipated in the first half of 2025[5]. - ALTO-203 is also on track for its Phase 2 proof-of-concept trial, with approximately 60 patients expected to be enrolled and topline data expected in the first half of 2025[6]. - ALTO-101's Phase 2 proof-of-concept trial is ongoing, with topline data expected by the end of 2025[7]. - ALTO-100 did not achieve the primary outcome in its Phase 2b study for MDD, but showed a clinically meaningful effect in a pre-specified analysis of biomarker-positive patients[3]. Financial Position - The company has a strong cash position of approximately $182 million, expected to fund operations into 2027[10]. - Cash, cash equivalents, and restricted cash as of September 30, 2024, totaled $182,201,000, significantly up from $82,548,000 at December 31, 2023, marking a 120.5% increase[19]. - Total assets increased to $191,608,000 as of September 30, 2024, compared to $86,628,000 at the end of 2023, representing a 120.5% growth[19]. - Total liabilities rose to $26,556,000 as of September 30, 2024, compared to $16,823,000 at December 31, 2023, indicating a 58.0% increase[19]. - The accumulated deficit increased to $(123,195,000) as of September 30, 2024, from $(76,965,000) at the end of 2023, reflecting a 60.0% increase[19]. Operating Expenses - General and administrative expenses for Q3 2024 were $5.8 million, compared to $1.8 million in Q3 2023, driven by increased headcount and operational requirements[12]. - Total operating expenses for the nine months ended September 30, 2024, were $51,613,000, up from $26,044,000 in 2023, indicating a 97.9% increase[18].

Core Viewpoint - Alto Neuroscience's Phase 2b study of ALTO-100 for major depressive disorder did not meet its primary endpoint, leading to a significant drop in share price [2]. Investigation Details - On October 22, 2024, Alto Neuroscience announced that the Phase 2b study did not achieve its primary endpoint as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo [2]. - Following this announcement, shares of Alto Neuroscience fell by nearly 60% during after-hours trading on the same day [2]. Next Steps - Investors who purchased Alto Neuroscience securities and have relevant information are encouraged to assist the investigation by visiting the firm's website [3]. - Contact information for the firm's representatives is provided for those who wish to contribute to the investigation [3]. Legal Representation - The firm represents investors in class actions on a contingency fee basis, meaning they will only seek reimbursement for expenses and attorneys' fees if successful [4]. Firm Background - Bronstein, Gewirtz & Grossman, LLC is a nationally recognized firm specializing in securities fraud class actions and has recovered hundreds of millions of dollars for investors [5].

On Tuesday, Alto Neuroscience, Inc. ANRO revealed that the Phase 2b study of ALTO-100 for major depressive disorder (MDD) did not meet its primary endpoint compared to placebo.The biomarker-defined major depressive disorder patient group treated with ALTO-100 did not demonstrate a statistically significant improvement in depressive symptoms compared to placebo.ALTO-100 did not demonstrate a benefit over the placebo on the pre-specified key secondary analyses.Also Read: Treatment Patch For Schizophrenia: New ...