Group 1 - A shareholder class action lawsuit has been filed against Alto Neuroscience, Inc. alleging that the company made materially false and/or misleading statements regarding its business and operations [1] - The lawsuit claims that ALTO-100 was less effective in treating Major Depressive Disorder (MDD) than previously communicated to investors, leading to overstated clinical, regulatory, and commercial prospects [1] - As a result of these allegations, the lawsuit asserts that Alto's overall business and financial prospects were also overstated [1] Group 2 - Investors who purchased shares of Alto between February 2, 2024, and October 22, 2024, and suffered significant losses are encouraged to discuss their legal rights [2] - The deadline for investors to request to be appointed as lead plaintiff in the case is September 19, 2025 [3] - Holzer & Holzer, LLC is a law firm specializing in representing shareholders and has a history of recovering significant amounts for investors affected by corporate misconduct [3]

NEW YORK, July 22, 2025 (GLOBE NEWSWIRE) -- Gainey McKenna & Egleston announces that a securities class action lawsuit has been filed in the United States District Court for the Northern District of California on behalf of all persons or entities who purchased or otherwise acquired Alto Neuroscience, Inc. (“Alto Neuroscience” or the “Company”) (NYSE: ANRO) (i) between February 2, 2024 and October 22, 2024, inclusive (the “Class Period”); and/or (ii) pursuant and/or traceable to Alto Neuroscience’s registrat ...

Core Viewpoint - A class action lawsuit has been filed against Alto Neuroscience, Inc. for allegedly misleading investors regarding the effectiveness of its drug candidate ALTO-100 during its IPO and subsequent period [1][2]. Group 1: Company Overview - Alto Neuroscience, Inc. is a clinical-stage biopharmaceutical company based in the U.S. with a product pipeline that includes ALTO-100, which was in a Phase 2b clinical trial for treating major depressive disorder (MDD) at the time of its IPO [1]. - The IPO occurred on or about February 2, 2024, and the class period for the lawsuit extends from this date to October 22, 2024 [1]. Group 2: Allegations and Misleading Information - The lawsuit alleges that the Offering Documents related to the IPO were negligently prepared and that the company failed to disclose critical information about ALTO-100's effectiveness [2]. - Specifically, it is claimed that ALTO-100 was less effective in treating MDD than represented, leading to overstated clinical, regulatory, and commercial prospects, which in turn inflated Alto's business and financial outlook [2]. Group 3: Impact of Clinical Trial Results - On October 22, 2024, Alto announced that ALTO-100 did not meet its primary endpoint in the Phase 2b trial, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo [3]. - Following this announcement, Alto's stock price plummeted by $10.17 per share, a decrease of 69.99%, closing at $4.36 per share on October 23, 2024 [3]. Group 4: Legal Proceedings - Shareholders interested in participating in the class action have until September 19, 2025, to seek lead plaintiff status, which allows them to represent other class members in the litigation [4]. - Participation in the case is not required to be eligible for recovery, and shareholders can choose to remain absent class members [4].

Summary of Alto Neuroscience (ANRO) FY Conference - June 17, 2025 Company Overview - **Company**: Alto Neuroscience - **Industry**: Clinical stage biopharmaceutical company focused on precision psychiatry through biomarker-guided drug development - **Pipeline**: Five phase two programs targeting depression, bipolar disorder, and schizophrenia using a proprietary platform that integrates EEG, cognitive assessments, and wearable data to optimize patient treatment matching [2][8] Core Points and Arguments Challenges in Psychiatry - Traditional psychiatric treatments often lack data-driven selection, relying on historical responses from patients or family members [3][9] - There is a significant gap in understanding which treatments work for specific patients and the underlying reasons [3][9] Precision Psychiatry Approach - Alto Neuroscience aims to address these challenges by utilizing biomarkers to understand drug effects on brain functions related to psychiatric disorders [4][10] - The company employs biomarkers to determine drug efficacy and predict patient responses, thereby reducing risks in drug development [5][12] Clinical Programs and Prioritization - Alto has five clinical stage programs, with a focus on late-stage trials that leverage existing data to inform patient selection and drug efficacy [13][14] - The company is broadening its representation of psychopathology, including various forms of depression and cognitive impairment in schizophrenia [14][15] FDA Guidance and Digital Biomarkers - Alto aligns its strategies with evolving FDA guidance on enrichment strategies in psychiatry trials, particularly regarding digital biomarkers [17][19] - The company has engaged with the FDA to ensure its biomarker strategies are scientifically sound and regulatory compliant [19] Alto 207 - Dopamine Agonist for Treatment-Resistant Depression (TRD) - Alto 207 is positioned as a next-generation dopamine agonist, differentiating itself from existing treatments by directly stimulating the dopamine system [20][21] - The combination of pramipexole (a D3-preferring dopamine agonist) with ondansetron (an antiemetic) aims to mitigate side effects like nausea and vomiting, allowing for faster and higher dosing [22][23] - The program is set to enter a late-stage phase 2b trial, with promising preliminary data indicating significant antidepressant efficacy [23][26] Upcoming Trials and Expectations - The phase 2b trial for Alto 207 is designed to support registration, with expectations for interactions with the FDA to clarify pivotal design [30][31] - The company anticipates a broad TRD label, with biomarkers serving as adjuncts to enhance clinical decision-making [27][28] Other Pipeline Developments - **Alto 203**: An early-stage program using an H3 inverse agonist strategy, focusing on subjective response and cognition [36][37] - **Alto 101**: Targets cognitive impairment associated with schizophrenia, utilizing a transdermal formulation to improve tolerability [41][43] - **Alto 300**: An approved antidepressant in Europe, being developed in the US with a focus on biomarker-defined patient populations [46][48] Market Positioning - Alto 207 is expected to compete favorably against existing treatments like SPRAVATO, with advantages in efficacy, safety profile, and ease of use [34][35] - The company aims to address a significant unmet need in the TRD population, estimated at three million patients in the US annually [32][33] Important but Overlooked Content - The company emphasizes the importance of rigorous patient selection and compliance monitoring to ensure trial integrity and data quality [56][58] - Alto is implementing advanced AI tools to enhance patient profiling and trial execution, aiming to mitigate risks associated with noncompliance and professional patients [58] This summary encapsulates the key insights from the conference, highlighting Alto Neuroscience's innovative approach to psychiatric treatment and its strategic positioning within the biopharmaceutical industry.

Summary of Alto Neuroscience (ANRO) Conference Call Company Overview - **Company**: Alto Neuroscience - **Focus**: Precision psychiatry, aiming to understand individual brain biology to guide treatment development and patient selection [4][5] Key Points and Arguments Precision Psychiatry Approach - Alto Neuroscience employs a precision psychiatry approach, focusing on understanding the biology of individual patients to improve treatment outcomes [4] - The company identifies a significant need for innovation in psychiatry, given the high prevalence of mental health issues and limited advancements [4] Biomarkers and Drug Development - All programs incorporate biomarkers to enhance patient selection and treatment efficacy [5] - The company is developing multiple phase 2B studies, utilizing biomarkers to define patient populations that will benefit from treatments [6] FDA Interaction and Regulatory Strategy - The FDA is primarily concerned with clear patient definitions and inclusion/exclusion criteria, which Alto believes can be effectively addressed through their biomarker approach [12][14] - The company has engaged with the FDA regarding their programs, indicating a supportive stance if the biomarker rationale is clear [14] Recent Acquisition - Alto recently acquired a new asset, Alto 207, a fixed-dose combination of pramipexole and ondansetron, aimed at treating treatment-resistant depression (TRD) [15][16] - The combination is designed to enhance antidepressant efficacy while minimizing side effects, allowing for faster titration [16][19] Clinical Data and Efficacy - Initial studies show promising results for the combination, with a significant effect size on MADRS scores, indicating potential for rapid effects in TRD patients [22][23] - The study demonstrated a Cohen's D of 1.1, with an eight-point difference in MADRS scores between drug and placebo at eight weeks [23] Future Plans and Trials - Phase 2B trials for Alto 207 are set to begin in the first half of next year, with results expected in 2027 [26] - The company has sufficient cash runway into 2028, allowing for multiple upcoming catalysts, including three phase 2B trials [55] Other Programs - Alto is also developing an H3 inverse agonist compound, with a focus on pharmacodynamics and cognitive benefits [34][35] - The company is exploring biomarkers for cognitive impairment in schizophrenia, specifically using EEG to measure treatment effects [47][49] Additional Important Insights - The company emphasizes the importance of selecting the right patient populations based on cognitive impairment metrics, which could enhance the efficacy of treatments [50] - Alto's strategy includes leveraging existing safety data to streamline the regulatory pathway for new drug combinations [31][32] - The potential for complementary biomarkers to improve treatment outcomes and payer acceptance is a key aspect of Alto's strategy [30] This summary encapsulates the critical insights from the conference call, highlighting Alto Neuroscience's innovative approach to psychiatric treatment and its strategic plans for future development.

Alto Neuroscience (ANRO) Update / Briefing June 03, 2025 08:00 AM ET Speaker0 Good morning, and welcome to the Alto Neuroscience Investor Conference Call to discuss the company's acquisition of a novel dopamine agonist combination product candidate. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now turn the call over to Amit Edkin, Founder ...

Part I - Financial Information [Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The unaudited condensed consolidated financial statements for Q1 2025 reflect a net loss of $15.2 million, a decrease in total assets, and an increase in total liabilities, with $160.8 million in cash Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $160,754 | $168,229 | | Total assets | $171,915 | $177,542 | | Total liabilities | $32,819 | $26,082 | | Total stockholders' equity | $139,096 | $151,460 | Condensed Consolidated Statement of Operations Highlights (in thousands) | Account | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $9,974 | $9,952 | | General and administrative | $5,702 | $4,434 | | Loss from operations | $(15,676) | $(14,386) | | Net loss | $(15,169) | $(13,417) | | Net loss per share, basic and diluted | $(0.56) | $(0.76) | Condensed Consolidated Statement of Cash Flows Highlights (in thousands) | Activity | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(16,556) | $(10,983) | | Net cash used in investing activities | $(24) | $(224) | | Net cash provided by financing activities | $9,127 | $134,559 | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's clinical-stage biopharmaceutical business, its accumulated deficit of $153.6 million, and key financing activities including an amended $75.0 million loan and an $11.7 million convertible grant - The company is a clinical-stage biopharmaceutical firm developing personalized psychiatry treatments with **five clinical-stage assets** in its pipeline[28](index=28&type=chunk) - As of March 31, 2025, the company reported an **accumulated deficit of approximately $153.6 million**, primarily funded through equity financings including **$133.0 million net proceeds from its February 2024 IPO**[29](index=29&type=chunk)[30](index=30&type=chunk) - In January 2025, the company amended its loan agreement with K2 HealthVentures, increasing the total term loan facility to **$75.0 million** and drawing **$20.0 million**[46](index=46&type=chunk)[48](index=48&type=chunk) - A convertible grant agreement with The Wellcome Trust Limited, signed in July 2024, provides up to **$11.7 million** for ALTO-100 development, with **$1.3 million drawn** as of March 31, 2025[64](index=64&type=chunk) - The company holds multiple license and asset purchase agreements requiring potential future milestone and royalty payments upon achieving development, regulatory, and commercial targets[73](index=73&type=chunk)[77](index=77&type=chunk)[83](index=83&type=chunk)[89](index=89&type=chunk)[92](index=92&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's clinical-stage biopharmaceutical operations, reporting a net loss of $15.2 million for Q1 2025, and projects sufficient cash resources of $161.3 million to fund operations into 2028 - The company's pipeline includes **five clinical-stage assets**: ALTO-100 (BPD), ALTO-300 (MDD), ALTO-203 (MDD with anhedonia), ALTO-101 (CIAS), and ALTO-202 (MDD)[140](index=140&type=chunk) Key Clinical Trial Updates and Expected Data Readouts | Product Candidate | Indication | Status | Expected Topline Data | | :--- | :--- | :--- | :--- | | ALTO-100 | BPD | Phase 2b Enrollment Ongoing | H2 2026 | | ALTO-300 | MDD | Phase 2b Enrollment Ongoing | Mid-2026 | | ALTO-203 | MDD | Phase 2 POC Enrollment Complete | Q2 2025 | | ALTO-101 | CIAS | Phase 2 POC | H2 2025 | - The company held **$161.3 million in cash, cash equivalents, and restricted cash** as of March 31, 2025, projected to fund operations into **2028**[160](index=160&type=chunk)[199](index=199&type=chunk) - Net loss for Q1 2025 was **$15.2 million**, an increase from **$13.4 million** in Q1 2024, primarily due to higher G&A costs and a **$0.7 million loss on debt extinguishment**[155](index=155&type=chunk)[173](index=173&type=chunk)[176](index=176&type=chunk) [Results of Operations](index=36&type=section&id=Results%20of%20Operations) Total operating expenses increased to $15.7 million in Q1 2025, driven by a $1.3 million rise in general and administrative expenses and a $0.7 million loss on debt extinguishment, while research and development costs remained stable Research and Development Expenses by Program (in thousands) | Program | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | ALTO-100 | $1,124 | $2,207 | $(1,083) | | ALTO-300 | $922 | $1,116 | $(194) | | ALTO-101 | $969 | $406 | $563 | | ALTO-203 | $737 | $620 | $117 | | Personnel-related costs | $5,093 | $4,353 | $740 | | **Total R&D** | **$9,974** | **$9,952** | **$22** | - General and administrative expenses increased by **$1.3 million**, from $4.4 million in Q1 2024 to **$5.7 million** in Q1 2025, primarily due to higher personnel costs and professional fees associated with public company operations[175](index=175&type=chunk) - Other income, net, decreased by **$0.5 million**, mainly due to a **$0.7 million loss on debt extinguishment** in Q1 2025[176](index=176&type=chunk) [Liquidity and Capital Resources](index=37&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company held $161.3 million in cash, cash equivalents, and restricted cash, with operations funded by IPO proceeds and debt facilities, projected to be sufficient into 2028 - The company held **$161.3 million in cash, cash equivalents, and restricted cash** as of March 31, 2025[178](index=178&type=chunk) - In January 2025, the company amended its loan agreement, increasing the total facility to **$75.0 million** and drawing **$20.0 million**, with approximately **$10.0 million** used for refinancing[179](index=179&type=chunk)[182](index=182&type=chunk) - In July 2024, the company secured a convertible grant agreement with Wellcome for up to approximately **$11.7 million** to fund ALTO-100 development[190](index=190&type=chunk) - Net cash used in operating activities increased to **$16.6 million** in Q1 2025 from **$11.0 million** in Q1 2024, mainly due to timing of bonus payments and higher operational spending[195](index=195&type=chunk) - Net cash from financing activities was **$9.1 million** in Q1 2025 from new loan proceeds, compared to **$134.6 million** in Q1 2024 from the IPO[197](index=197&type=chunk)[198](index=198&type=chunk) - Management projects current cash and equivalents will sufficiently fund operating expenses and capital requirements into **2028**[199](index=199&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=43&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, the company is exempt from providing quantitative and qualitative disclosures about market risk - As a smaller reporting company, Alto Neuroscience, Inc. is not required to provide quantitative and qualitative disclosures about market risk[220](index=220&type=chunk) [Controls and Procedures](index=43&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal control over financial reporting during the quarter - The Principal Executive Officer and Principal Financial Officer concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level as of March 31, 2025[221](index=221&type=chunk)[222](index=222&type=chunk) - No material changes occurred in internal control over financial reporting during Q1 2025[223](index=223&type=chunk) Part II - Other Information [Legal Proceedings](index=45&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any legal proceedings expected to have a material adverse effect on its business - As of the report date, the company is not involved in any legal proceedings expected to have a material adverse effect on the business[227](index=227&type=chunk) [Risk Factors](index=45&type=section&id=Item%201A.%20Risk%20Factors) No material changes have occurred to the risk factors previously disclosed in the company's Annual Report on Form 10-K - No material changes have occurred to the risk factors previously disclosed in the company's Annual Report[228](index=228&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=45&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports no unregistered sales of equity securities and no material change in the planned use of **$133.0 million** net proceeds from its February 2024 IPO - The company's IPO closed on February 6, 2024, generating **$133.0 million in net proceeds** from the sale of **9,246,000 shares** at **$16.00 per share**[230](index=230&type=chunk)[231](index=231&type=chunk) - No material change has occurred in the planned use of IPO proceeds[231](index=231&type=chunk) [Defaults Upon Senior Securities](index=45&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) Not applicable [Mine Safety Disclosures](index=45&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable [Other Information](index=45&type=section&id=Item%205.%20Other%20Information) Not applicable [Exhibits](index=46&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including corporate governance documents, financial agreements, and officer certifications

[Recent Business Highlights](index=1&type=section&id=Recent%20Business%20Highlights) Alto Neuroscience reported progress on its four clinical trials in Q1 2025, with key data readouts expected from 2025 through 2026, highlighting advancements in its biomarker platform and maintaining a strong cash position of $161.3 million, expected to fund operations into 2028 and through at least four upcoming clinical study readouts - Phase 2 proof-of-concept trial topline data for **ALTO-203** in MDD is expected in **Q2 2025**, followed by **ALTO-101** in schizophrenia in **H2 2025**[1](index=1&type=chunk) - Late-stage Phase 2b trial data for **ALTO-300** in MDD is anticipated in **mid-2026**, and for **ALTO-100** in bipolar depression in **H2 2026**[1](index=1&type=chunk) - The company possesses a strong cash position of approximately **$161.3 million**, which is projected to fund planned operations into **2028**[1](index=1&type=chunk) - Alto continues to advance its biomarker platform, presenting new data on an EEG-based placebo response biomarker and dopamine-related biomarkers to support its precision psychiatry approach[2](index=2&type=chunk) [Pipeline Highlights](index=1&type=section&id=Pipeline%20Highlights) Alto Neuroscience is advancing four clinical-stage programs for various neuropsychiatric disorders, with ALTO-100 and ALTO-300 in Phase 2b trials for bipolar depression and MDD respectively, and ALTO-203 and ALTO-101 in Phase 2 proof-of-concept trials, all supported by a biomarker-driven approach to patient stratification [ALTO-100 for Bipolar Depression (BPD)](index=1&type=section&id=ALTO-100) ALTO-100 is a first-in-class oral small molecule for BPD, currently in Phase 2b trials with data expected in H2 2026, utilizing an EEG-based biomarker - **ALTO-100** is a first-in-class oral small molecule being developed for BPD in patients identified by a cognitive biomarker[3](index=3&type=chunk) - Enrollment is ongoing in the Phase 2b trial, with topline data from approximately **200 patients** expected in the **second half of 2026**. The primary endpoint is the change from baseline on the MADRS[3](index=3&type=chunk) - The company is utilizing a prospectively validated EEG-based biomarker to account for potential placebo responders, which is expected to improve the detection of treatment response[3](index=3&type=chunk)[4](index=4&type=chunk) [ALTO-300 for Major Depressive Disorder (MDD)](index=2&type=section&id=ALTO-300) ALTO-300, an adjunctive treatment for MDD, is in a Phase 2b trial with topline data anticipated in mid-2026, showing a favorable safety profile - **ALTO-300** (agomelatine 25mg) is being developed as an adjunctive treatment for MDD in patients characterized by an EEG biomarker[5](index=5&type=chunk) - Topline data from the Phase 2b trial, enrolling approximately **200 biomarker-positive patients**, is expected in **mid-2026**[7](index=7&type=chunk) - The **25mg dose** has demonstrated a favorable safety profile, with no liver enzyme elevations (≥ 3 times the upper limit of normal) observed in the completed **239-patient Phase 2a trial** or the ongoing Phase 2b trial[7](index=7&type=chunk) [ALTO-203 for Major Depressive Disorder (MDD)](index=2&type=section&id=ALTO-203) ALTO-203, a novel histamine H3 inverse agonist for MDD patients with anhedonia, has completed enrollment in its Phase 2 POC trial with data expected in Q2 2025 - **ALTO-203** is a novel histamine H3 inverse agonist being developed for MDD patients with high levels of anhedonia[6](index=6&type=chunk) - Enrollment in the **69-patient Phase 2 proof-of-concept (POC) trial** is complete, with topline data expected in the **second quarter of 2025**[6](index=6&type=chunk) - New preclinical data showed **ALTO-203** effectively reversed anhedonia-like behavior, an effect not seen with pitolisant, the only FDA-approved H3R inverse agonist[11](index=11&type=chunk) [ALTO-101 for Cognitive Impairment Associated with Schizophrenia (CIAS)](index=3&type=section&id=ALTO-101) ALTO-101, a transdermal PDE4 inhibitor for CIAS, is undergoing a Phase 2 POC trial with topline data anticipated in H2 2025, showing enhanced theta responses - **ALTO-101** is a novel transdermal formulation of a PDE4 inhibitor being developed for CIAS[9](index=9&type=chunk) - Enrollment is ongoing in the Phase 2 POC trial, with topline data expected in the **second half of 2025**[11](index=11&type=chunk) - The primary outcome is the effect on theta band activity, an EEG measure associated with CIAS. Recent data demonstrated that **ALTO-101** significantly enhanced theta responses in humans[11](index=11&type=chunk) [Upcoming Milestones and Events](index=3&type=section&id=Upcoming%20Milestones%20and%20Events) Alto Neuroscience outlined a clear timeline of four major clinical trial data readouts scheduled from the second quarter of 2025 through the second half of 2026, with plans to present at four scientific and investor conferences in May and June 2025 Upcoming Clinical Trial Data Readouts | Expected Milestone | Timing | | :--- | :--- | | ALTO-203 Phase 2 POC MDD trial topline data | 2Q 2025 | | ALTO-101 Phase 2 POC CIAS trial topline data | 2H 2025 | | ALTO-300 Phase 2b MDD trial topline data | Mid-2026 | | ALTO-100 Phase 2b BPD trial topline data | 2H 2026 | - The company is scheduled to present at several upcoming conferences: American Society of Clinical Psychopharmacology (ASCP) Annual Meeting (May 27-30, 2025), Jefferies Healthcare Conference (June 3-5, 2025), H.C. Wainwright 6th Annual Neuro Perspectives Hybrid Conference (June 16-17, 2025), and Biotechnology Innovation Organization (BIO) International Convention (June 16-19, 2025)[11](index=11&type=chunk) [First Quarter 2025 Financial Highlights](index=4&type=section&id=First%20Quarter%202025%20Financial%20Highlights) For the first quarter of 2025, Alto Neuroscience reported a net loss of $15.2 million, maintained a strong cash position of $161.3 million sufficient to fund operations into 2028, with research and development expenses remaining flat year-over-year while general and administrative expenses increased primarily due to higher headcount and public company costs Key Financial Metrics | Financial Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | R&D Expenses | $10.0 million | $10.0 million | | G&A Expenses | $5.7 million | $4.4 million | | Net Loss | $15.2 million | $13.4 million | - Cash, cash equivalents, and restricted cash was approximately **$161.3 million** as of March 31, 2025, compared to **$168.7 million** as of December 31, 2024[12](index=12&type=chunk) - The increase in G&A expenses was mainly due to higher headcount, expanded operational requirements, and public company operating costs, including **$0.3 million** in non-cash, stock-based compensation[14](index=14&type=chunk) [Financial Statements](index=6&type=section&id=Financial%20Statements) The condensed consolidated financial statements for Q1 2025 show a net loss of $15.2 million, an increase from the $13.4 million loss in Q1 2024, with total assets at $171.9 million as of March 31, 2025, a slight decrease from $177.5 million at the end of 2024, and total liabilities increasing to $32.8 million [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The Condensed Consolidated Statements of Operations and Comprehensive Loss for Q1 2025 show a net loss of $15.2 million, an increase from $13.4 million in Q1 2024, with total operating expenses rising to $15.7 million | (in thousands, except per share) | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $9,974 | $9,952 | | General and administrative | $5,702 | $4,434 | | **Total operating expenses** | **$15,676** | **$14,386** | | **Loss from operations** | **$(15,676)** | **$(14,386)** | | Interest income | $1,827 | $1,558 | | **Net loss** | **$(15,169)** | **$(13,417)** | | **Net loss per share, basic and diluted** | **$(0.56)** | **$(0.76)** | | Weighted-average shares outstanding | 27,049 | 17,600 | [Selected Condensed Consolidated Balance Sheet Data](index=6&type=section&id=Selected%20Condensed%20Consolidated%20Balance%20Sheet%20Data) Selected Condensed Consolidated Balance Sheet Data as of March 31, 2025, indicates total assets of $171.9 million and total liabilities of $32.8 million, with cash decreasing from year-end 2024 | (in thousands) | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents, and restricted cash | $161,254 | $168,729 | | **Total assets** | **$171,915** | **$177,542** | | **Total liabilities** | **$32,819** | **$26,082** | | Accumulated deficit | $(153,565) | $(138,396) |

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].