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Business Wire
7 days ago
- Business
- Business Wire
Alto Neuroscience Identifies Biomarker and Reports Positive Pharmacodynamic Results from Exploratory Phase 2 Proof-of-Concept Trial of ALTO-203
MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Alto Neuroscience, Inc. ('Alto') (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced the identification of a patient selection biomarker and positive pharmacodynamic results from its exploratory Phase 2 proof-of-concept (POC) trial of ALTO-203 in major depressive disorder (MDD) patients with elevated levels of anhedonia. ALTO-203 is a novel, oral, histamine H3 inverse agonist, designed to modulate circuits underlying cognition, wakefulness, and alertness. The profile exhibited by ALTO-203 in the exploratory POC trial demonstrated clear effects on objective measures of attention and wakefulness, with observed improvements linked to changes in the EEG theta/beta ratio—a biomarker indexing cortical arousal and attentional control. These findings replicate results from the Phase 1 study in healthy volunteers, where ALTO-203 treatment led to improvements in sustained attention and reductions in the EEG theta/beta ratio. Baseline EEG theta/beta ratio predicted attentional benefits of ALTO-203 in both the Phase 1 study and Phase 2 POC trial. 'We aim to leverage objective biomarkers to enable targeted neuropsychiatric drug development so that patients can get better, faster,' said Amit Etkin, M.D., Ph.D., founder and CEO of Alto Neuroscience. 'In this exploratory trial, we identified a robust biomarker for ALTO-203, EEG high-theta/beta ratio, which is a well-validated measure of abnormal cortical arousal and poor attentional control. Notably, this biomarker is FDA-cleared for use alongside clinical evaluation in the diagnosis of ADHD, reinforcing its clinical relevance. These positive results replicate findings from an ALTO-203 Phase 1 study and enhance our understanding of the patient subtypes most likely to benefit from the drug, further strengthening the foundation of our precision psychiatry approach. We believe our platform has the potential to enable data-driven indication selection and trial design early in development—accelerating the path to more effective, personalized treatment.' The exploratory Phase 2 POC trial, which enrolled 69 patients, was conducted in two sequential, double-blind, placebo-controlled periods. The trial was designed to characterize the pharmacodynamic, pharmacokinetic, safety, and tolerability profile of ALTO-203 across two dose levels compared to placebo in a crossover design and was not powered to detect statistical significance on traditional depression outcome scales (e.g., MADRS). Adam Savitz, M.D., Ph.D., Chief Medical Officer of Alto Neuroscience, commented, 'We are encouraged by the positive pharmacodynamic activity observed in the study, which aligns with the proposed mechanism of ALTO-203. The wake-promoting and pro-cognitive effects demonstrated, suggest clear potential for ALTO-203 to be a meaningful treatment across various neuropsychiatric conditions in which sleep and attention are significantly impaired.' Topline, prespecified results from the exploratory Phase 2 POC trial of ALTO-203 include: Subjective Effects on Bond & Lader Visual Analog Scale (BL-VAS): Patients reported significant improvements from baseline on BL-VAS for alertness & mood at the 5-hour timepoint post dosing with ALTO-203. A higher-than-expected placebo response was observed on the Bond & Lader measurements – no significant separation between ALTO-203 and placebo was observed. EEG Biomarker of Drug Effect Identified: The theta/beta ratio, a neurophysiological marker linked to attentional control, was confirmed as a key pharmacodynamic readout. The effects of ALTO-203 on reducing theta/beta ratio were significant compared to placebo (25µg: p<0.05). This marker was previously shown to be significantly reduced by ALTO-203 in the completed Phase 1 study in healthy subjects, as well as in preclinical studies. Cognitive Enhancement Observed: ALTO-203 treatment led to significant improvements in sustained attention (25µg: p<0.05; 75µg: p=0.06 vs. placebo), aligning with reductions in the EEG theta/beta ratio. Improvement in attention was greatest in patients with high baseline theta/beta ratios (i.e., more abnormal) (25µg: p<0.01; 75µg: p<0.05 vs. placebo). The observed improvements in attention and corresponding changes in EEG theta/beta ratio replicated significant findings from the Phase 1 study. Wearable Device Confirmation: Objective sleep measures from wearable devices supported the wake-promoting effects of ALTO-203, and the increased wakefulness exhibited by ALTO-203 was significant for both doses (25µg: p<0.05; 75µg: p<0.001 vs. placebo). Pharmacokinetics and Safety: ALTO-203 displayed predictable accumulation over multiple doses with no adverse pharmacokinetic signals. ALTO-203 was well tolerated, with insomnia as the most frequent adverse event, consistent with its wake-promoting profile. MADRS Improvements: Patients taking 25µg of ALTO-203 exhibited a mean improvement of 2 points at week 3 and 0.9 points at week 4 compared to placebo. The differences were not observed in the 75µg dose group. MADRS improvements were evaluated during the 28-day multi-dose period, which was not powered to detect significance. Alto plans to report additional results from this exploratory study at a future medical meeting and expects to determine the next development steps for ALTO-203 following the complete analysis of the data set. About the Phase 2 POC Trial of ALTO-203 The Phase 2 POC trial enrolled 69 MDD patients with higher levels of anhedonia consisted of two dosing periods (63 completed the primary single-dose period): Single-dose period: Patients received two single-doses of ALTO-203 (25µg and 75µg), and placebo in a randomized, three-way crossover design. The powered primary outcome was an acute change in positive emotion assessed by the alertness and mood components of the Bond-Lader Visual Analog Scale (BL-VAS), an established scale of subjective feelings. Key pre-specified exploratory outcomes included measures of cognition, EEG changes, and effects on sleep. Multi-dose period: Patients were randomized to receive daily administration of ALTO-203 (25µg or 75µg QD) or placebo over 28 days. This period was designed to evaluate extended safety, tolerability, and pharmacokinetics, as well as exploratory biomarkers across EEG, cognitive testing, and wearable device data. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto's Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto's clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression (TRD), and schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as 'expects,' 'plans,' 'will' and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto's expectations about the potential benefits, activity, effectiveness and safety of its product candidates and Precision Psychiatry Platform ('Platform'); the reproducibility of any favorable results seen in the exploratory Phase 2 POC trial of ALTO-203 in major depressive disorder; and Alto's expectations with regard to the design and results of its clinical trials. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto's actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled 'Risk Factors' in Alto's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the Securities and Exchange Commission ('SEC') as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto's Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website.
Yahoo
03-06-2025
- Business
- Yahoo
Alto Neuroscience Adds 'Intriguing' Depression Asset Via Over $100 Million Deal
On Tuesday, Alto Neuroscience, Inc. (NASDAQ:ANRO) announced an asset purchase agreement with Chase Therapeutics Corporation for a portfolio of dopamine agonist drug combinations for treatment-resistant depression (TRD), generally defined as a failure on two or more antidepressants. Alto paid Chase Therapeutics an upfront payment of $1.75 million. Chase Therapeutics will be eligible for up to $71.5 million in milestone payments, $41 million of the potential future milestone payments are tied to the product candidates' commercial success. Alto expects its current cash balance to support planned operations into 2028 through five clinical trial readouts across its pipeline most advanced program, ALTO-207 (formerly known as CTC-501), is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for Parkinson's disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 enables rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. Phase 2a trial of CTC-501 Chase Therapeutics completed a Phase 2a trial evaluating CTC-501 in 32 patients with depression. The primary endpoint was achieved in the study. Patients randomized to receive CTC-501 reached a mean dose of 4.1mg per day, with 67% achieving the highest allowable dose of 5mg/day. CTC-501 was generally well tolerated in the maintenance period of the study. CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms as measured by the Montgomery Åsberg Depression Rating Scale or MADRS. CTC-501 also demonstrated significantly greater improvement on the Clinician Global Impression Scale of Severity (CGI-S) compared to placebo. Alto expects to initiate a Phase 2b trial, designed to be a potentially pivotal study, with ALTO-207 in patients with TRD by mid-2026 and report topline data in 2027. Phase 2a Trial For CTC-413 ALTO-208 (or CTC-413) is a fixed-dose combination of pramipexole and aprepitant, an antiemetic, neurokinin-1 (NK-1) receptor antagonist. ALTO-208 is being developed for patients with Parkinson's disease (PD). Chase Therapeutics completed a blinded Phase 2a trial evaluating CTC-413 in 13 patients with PD. The mean tolerated dose of CTC-413 significantly exceeded pramipexole. Six subjects (67%) tolerated CTC-413 at the maximum dose of 9.0mg/day, and all but one remained on that dose throughout the final three-month treatment period. CTC-413 demonstrated favorable safety and tolerability with no unexpected, serious or persistent issues. William Blair reiterated an Outperform rating on Alto Neuroscience, viewing the acquisition of ALTO-207 as an 'intriguing asset.' The firm noted the impressive efficacy of pramipexole in the PAX-D study but also highlighted the possibility of functional unblinding in that study, which may have contributed to the perceived efficacy. Price Action: ANRO stock is trading higher by 2.31% to $2.66 at last check Tuesday Read Next:Photo by fizkes via Shutterstock Up Next: Transform your trading with Benzinga Edge's one-of-a-kind market trade ideas and tools. Click now to access unique insights that can set you ahead in today's competitive market. Get the latest stock analysis from Benzinga? This article Alto Neuroscience Adds 'Intriguing' Depression Asset Via Over $100 Million Deal originally appeared on © 2025 Benzinga does not provide investment advice. All rights reserved. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
03-06-2025
- Business
- Yahoo
Alto Neuroscience Announces Acquisition of Novel Dopamine Agonist Combination Product Candidate, Adding Late-Stage Readout in Treatment Resistant Depression Within Current Cash Runway
– ALTO-207 (fka CTC-501) is a fixed-dose combination of pramipexole and ondansetron designed to induce rapid antidepressant effects while mitigating dose-limiting adverse events of pramipexole – – Alto has generated proprietary insights on dopamine biomarkers in depression suggesting that direct dopamine receptor activation with ALTO-207 has the potential to be a differentiated therapeutic approach for treatment resistant depression (TRD) – – CTC-501 met primary and secondary endpoints in a completed Phase 2a study in MDD, demonstrating significantly greater improvements on MADRS compared to placebo (Week 8 Cohen's d = 1.1, p<0.05) – – Alto expects to initiate a Phase 2b trial, designed to be a potentially pivotal study, with ALTO-207 in patients with TRD by mid-2026 and report topline data in 2027 – – Cash guidance unchanged; current cash is expected to fund planned operations into 2028, through at least five planned clinical study readouts – – Company to host conference call and webcast today, June 3, at 8 a.m. ET – MOUNTAIN VIEW, Calif., June 03, 2025--(BUSINESS WIRE)--Alto Neuroscience, Inc. ("Alto") (NYSE: ANRO), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced that it entered into an asset purchase agreement with Chase Therapeutics Corporation for a portfolio of potentially best-in-class dopamine agonist drug combinations, including ALTO-207, formerly known as CTC-501, for treatment resistant depression (TRD), generally defined as a failure on two or more antidepressants. The most advanced program, ALTO-207 (formerly known as CTC-501), is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for the treatment of Parkinson's disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 is designed to enable rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. ALTO-207 is being developed to address the significant unmet need for patients with TRD. "The expansion of our pipeline aligns with Alto's mission to drive innovation in psychiatry through novel therapeutic solutions," said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. "With proprietary insights on dopamine biomarkers in depression that enable targeted neuropsychiatric drug development, we are uniquely positioned to advance ALTO-207, a differentiated, late-stage product candidate with robust clinical effects to date, which are supported with historical pramipexole data. The fixed-dose combination of pramipexole and ondansetron offers a novel treatment strategy designed to optimize for a rapid treatment effect with faster titration, and balance safety and tolerability at high doses. We believe the convenience of a single prescribable agent will also improve compliance and support clinician and patient adoption. Leveraging our targeted biomarker approach to stratify for TRD patients most likely to respond to treatment, we look forward to building on the positive Phase 2a results and initiating a Phase 2b trial, with a potentially pivotal design, by mid-2026." Dr. Etkin continued, "The strategic transaction with Chase Therapeutics allows us to add a major late-stage clinical readout to our pipeline without changing our current cash runway guidance into 2028. Broadly, we believe this opportunity underscores the robust value of our precision platform and bolsters our prospects for long-term growth through driving innovation in psychiatry." Thomas Chase, M.D., President and Chief Executive Officer of Chase Therapeutics Corporation, added, "Supported by the robust clinical effects in our completed Phase 2a study, we believe CTC-501, has the potential to address the critical need for more effective, mechanistically distinct interventions for patients with TRD. Given Alto's expertise in dopamine-related products in depression, we believe they are an ideal partner to maximize the therapeutic potential of our portfolio in depression and Parkinson's disease. We look forward to seeing Alto continue this exciting momentum as they work toward realizing our shared vision for patients." Michael Browning, DPhil, MRCP, MRCPsych, Professor of Computational Psychiatry, University of Oxford, commented, "I am highly encouraged by the recently completed PAX-D study of pramipexole, which suggests a greater and more durable effect than other available TRD treatments. However, pramipexole is not well tolerated and when it is, it requires slow titration due to dose-limiting AEs. The clinical utility of pramipexole would be greatly enhanced by improving the dose-limiting tolerability profile. Emerging data suggests that ALTO-207 could address these challenges, and be well positioned to treat this large and underserved patient population." Alto acquired CTC-501 (now ALTO-207), in development for depression, and CTC-413 (now ALTO-208), in development for Parkinson's disease. Both product candidates are novel patent-protected dopamine agonists. About the Completed Phase 2a Trial for CTC-501 Chase Therapeutics completed a randomized, placebo-controlled Phase 2a clinical trial evaluating CTC-501 in 32 patients with depression. The study consisted of two periods, a dose titration period in which patients were dosed with increasing dose levels of CTC-501 or placebo at increments of 1 mg/day (or matching placebo) until the maximum allowed dose (or first intolerable dose) was reached. Patients were then maintained for an eight-week treatment period at either the maximum allowed dose or their maximum tolerated dose (1 mg/day lower than their first intolerable dose in the titration period). The primary endpoint in the study was defined as overall tolerability and achievement of higher dose levels of pramipexole when combined with ondansetron. Clinical efficacy was evaluated as a secondary exploratory endpoint in the study. The primary endpoint was achieved in the study. Patients randomized to receive CTC-501 reached a mean dose of 4.1mg per day with 67% of patients achieving the highest allowable dose of 5mg/day. CTC-501 was generally well tolerated in the maintenance period of the study. The clinical efficacy measures were evaluated as secondary endpoints and across measures CTC-501 demonstrated large, clinically meaningful, effects. CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms as measured by the Montgomery Åsberg Depression Rating Scalef, or MADRS (LSM Δ vs. placebo at Week 8 = -8.2, p=0.025, Cohen's d=1.1). CTC-501 also demonstrated a significantly greater improvement compared to placebo on the Clinician Global Impression Scale of Severity, or CGI-S (LSM Δ vs. placebo at Week 8 = -0.76, p=0.04, Cohen's d=1.0). About the Completed Phase 2a Trial for CTC-413 ALTO-208 is a fixed-dose combination of pramipexole and aprepitant, an antiemetic, neurokinin-1 (NK-1) receptor antagonist. ALTO-208 is being developed for patients with Parkinson's disease (PD). Chase Therapeutics completed a blinded Phase 2a clinical trial evaluating CTC-413 (pramipexole co-administered with aprepitant) in 13 patients with PD. The study consisted of two periods. Patients in the treatment group were initially titrated to the maximum allowed dose of standard pramipexole extended release (4.5 mg/day). Patients were then switched to CTC-413 until the maximum allowed dose of 9mg/day (or first intolerable dose) was reached. Following three months of maintenance, patients returned to their pre-study regimen for final assessment. The mean tolerated dose of CTC-413 significantly exceeded pramipexole (p<0.001). Six subjects (67%) tolerated CTC-413 at the maximum dose of 9.0mg/day and all but one remained on that dose throughout the final three-month treatment period. CTC-413 demonstrated favorable safety and tolerability with no unexpected, serious or persistent issues. About the Transaction Under the terms of the asset purchase agreement, Alto paid Chase Therapeutics an upfront payment of $1.75 million, and Chase Therapeutics will be eligible for up to an aggregate of $71.5 million in future milestone payments related to prespecified development and commercial milestones. $41 million of the potential future milestone payments are tied to commercial success of the product candidates. Alto's financial guidance remains unchanged. The Company expects its current cash balance to support planned operations into 2028, now through five clinical trial readouts across its pipeline programs. Conference Call and Webcast at 8:00 a.m. ET Today Alto Neuroscience will host a conference call today at 8:00 a.m. ET to discuss the acquisition of a novel dopamine agonist combination product candidate. The call will feature Michael Browning, Professor of Computational Psychiatry at the University of Oxford, and Alan Schatzberg, M.D., Professor of Psychiatry and Behavioral Sciences at Stanford University. To listen to the live webcast, please visit Alto's investor relations website. Participants may register for the call here. A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company's website. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto's Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto's clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression (TRD), and schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as "expects," "plans," "will" and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto's expectations about the potential benefits, activity, effectiveness and safety of its product candidates and Precision Psychiatry Platform ("Platform"); Alto's expectations with regard to the design and results of its clinical trials; the reproducibility of positive clinical data seen in prior trials of CTC-501/ALTO-207; Alto's clinical and regulatory development plans for ALTO-207; the competitive landscape and potential market opportunities for ALTO-207; and Alto's anticipated cash runway. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto's actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled "Risk Factors" in Alto's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the Securities and Exchange Commission ("SEC") as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto's Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website. View source version on Contacts Investor and Media Contact: Mari Purpurainvestors@ media@ Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
03-06-2025
- Business
- Yahoo
Alto Neuroscience Announces Acquisition of Novel Dopamine Agonist Combination Product Candidate, Adding Late-Stage Readout in Treatment Resistant Depression Within Current Cash Runway
– ALTO-207 (fka CTC-501) is a fixed-dose combination of pramipexole and ondansetron designed to induce rapid antidepressant effects while mitigating dose-limiting adverse events of pramipexole – – Alto has generated proprietary insights on dopamine biomarkers in depression suggesting that direct dopamine receptor activation with ALTO-207 has the potential to be a differentiated therapeutic approach for treatment resistant depression (TRD) – – CTC-501 met primary and secondary endpoints in a completed Phase 2a study in MDD, demonstrating significantly greater improvements on MADRS compared to placebo (Week 8 Cohen's d = 1.1, p<0.05) – – Alto expects to initiate a Phase 2b trial, designed to be a potentially pivotal study, with ALTO-207 in patients with TRD by mid-2026 and report topline data in 2027 – – Cash guidance unchanged; current cash is expected to fund planned operations into 2028, through at least five planned clinical study readouts – – Company to host conference call and webcast today, June 3, at 8 a.m. ET – MOUNTAIN VIEW, Calif., June 03, 2025--(BUSINESS WIRE)--Alto Neuroscience, Inc. ("Alto") (NYSE: ANRO), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced that it entered into an asset purchase agreement with Chase Therapeutics Corporation for a portfolio of potentially best-in-class dopamine agonist drug combinations, including ALTO-207, formerly known as CTC-501, for treatment resistant depression (TRD), generally defined as a failure on two or more antidepressants. The most advanced program, ALTO-207 (formerly known as CTC-501), is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for the treatment of Parkinson's disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 is designed to enable rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. ALTO-207 is being developed to address the significant unmet need for patients with TRD. "The expansion of our pipeline aligns with Alto's mission to drive innovation in psychiatry through novel therapeutic solutions," said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. "With proprietary insights on dopamine biomarkers in depression that enable targeted neuropsychiatric drug development, we are uniquely positioned to advance ALTO-207, a differentiated, late-stage product candidate with robust clinical effects to date, which are supported with historical pramipexole data. The fixed-dose combination of pramipexole and ondansetron offers a novel treatment strategy designed to optimize for a rapid treatment effect with faster titration, and balance safety and tolerability at high doses. We believe the convenience of a single prescribable agent will also improve compliance and support clinician and patient adoption. Leveraging our targeted biomarker approach to stratify for TRD patients most likely to respond to treatment, we look forward to building on the positive Phase 2a results and initiating a Phase 2b trial, with a potentially pivotal design, by mid-2026." Dr. Etkin continued, "The strategic transaction with Chase Therapeutics allows us to add a major late-stage clinical readout to our pipeline without changing our current cash runway guidance into 2028. Broadly, we believe this opportunity underscores the robust value of our precision platform and bolsters our prospects for long-term growth through driving innovation in psychiatry." Thomas Chase, M.D., President and Chief Executive Officer of Chase Therapeutics Corporation, added, "Supported by the robust clinical effects in our completed Phase 2a study, we believe CTC-501, has the potential to address the critical need for more effective, mechanistically distinct interventions for patients with TRD. Given Alto's expertise in dopamine-related products in depression, we believe they are an ideal partner to maximize the therapeutic potential of our portfolio in depression and Parkinson's disease. We look forward to seeing Alto continue this exciting momentum as they work toward realizing our shared vision for patients." Michael Browning, DPhil, MRCP, MRCPsych, Professor of Computational Psychiatry, University of Oxford, commented, "I am highly encouraged by the recently completed PAX-D study of pramipexole, which suggests a greater and more durable effect than other available TRD treatments. However, pramipexole is not well tolerated and when it is, it requires slow titration due to dose-limiting AEs. The clinical utility of pramipexole would be greatly enhanced by improving the dose-limiting tolerability profile. Emerging data suggests that ALTO-207 could address these challenges, and be well positioned to treat this large and underserved patient population." Alto acquired CTC-501 (now ALTO-207), in development for depression, and CTC-413 (now ALTO-208), in development for Parkinson's disease. Both product candidates are novel patent-protected dopamine agonists. About the Completed Phase 2a Trial for CTC-501 Chase Therapeutics completed a randomized, placebo-controlled Phase 2a clinical trial evaluating CTC-501 in 32 patients with depression. The study consisted of two periods, a dose titration period in which patients were dosed with increasing dose levels of CTC-501 or placebo at increments of 1 mg/day (or matching placebo) until the maximum allowed dose (or first intolerable dose) was reached. Patients were then maintained for an eight-week treatment period at either the maximum allowed dose or their maximum tolerated dose (1 mg/day lower than their first intolerable dose in the titration period). The primary endpoint in the study was defined as overall tolerability and achievement of higher dose levels of pramipexole when combined with ondansetron. Clinical efficacy was evaluated as a secondary exploratory endpoint in the study. The primary endpoint was achieved in the study. Patients randomized to receive CTC-501 reached a mean dose of 4.1mg per day with 67% of patients achieving the highest allowable dose of 5mg/day. CTC-501 was generally well tolerated in the maintenance period of the study. The clinical efficacy measures were evaluated as secondary endpoints and across measures CTC-501 demonstrated large, clinically meaningful, effects. CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms as measured by the Montgomery Åsberg Depression Rating Scalef, or MADRS (LSM Δ vs. placebo at Week 8 = -8.2, p=0.025, Cohen's d=1.1). CTC-501 also demonstrated a significantly greater improvement compared to placebo on the Clinician Global Impression Scale of Severity, or CGI-S (LSM Δ vs. placebo at Week 8 = -0.76, p=0.04, Cohen's d=1.0). About the Completed Phase 2a Trial for CTC-413 ALTO-208 is a fixed-dose combination of pramipexole and aprepitant, an antiemetic, neurokinin-1 (NK-1) receptor antagonist. ALTO-208 is being developed for patients with Parkinson's disease (PD). Chase Therapeutics completed a blinded Phase 2a clinical trial evaluating CTC-413 (pramipexole co-administered with aprepitant) in 13 patients with PD. The study consisted of two periods. Patients in the treatment group were initially titrated to the maximum allowed dose of standard pramipexole extended release (4.5 mg/day). Patients were then switched to CTC-413 until the maximum allowed dose of 9mg/day (or first intolerable dose) was reached. Following three months of maintenance, patients returned to their pre-study regimen for final assessment. The mean tolerated dose of CTC-413 significantly exceeded pramipexole (p<0.001). Six subjects (67%) tolerated CTC-413 at the maximum dose of 9.0mg/day and all but one remained on that dose throughout the final three-month treatment period. CTC-413 demonstrated favorable safety and tolerability with no unexpected, serious or persistent issues. About the Transaction Under the terms of the asset purchase agreement, Alto paid Chase Therapeutics an upfront payment of $1.75 million, and Chase Therapeutics will be eligible for up to an aggregate of $71.5 million in future milestone payments related to prespecified development and commercial milestones. $41 million of the potential future milestone payments are tied to commercial success of the product candidates. Alto's financial guidance remains unchanged. The Company expects its current cash balance to support planned operations into 2028, now through five clinical trial readouts across its pipeline programs. Conference Call and Webcast at 8:00 a.m. ET Today Alto Neuroscience will host a conference call today at 8:00 a.m. ET to discuss the acquisition of a novel dopamine agonist combination product candidate. The call will feature Michael Browning, Professor of Computational Psychiatry at the University of Oxford, and Alan Schatzberg, M.D., Professor of Psychiatry and Behavioral Sciences at Stanford University. To listen to the live webcast, please visit Alto's investor relations website. Participants may register for the call here. A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company's website. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto's Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto's clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression (TRD), and schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as "expects," "plans," "will" and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto's expectations about the potential benefits, activity, effectiveness and safety of its product candidates and Precision Psychiatry Platform ("Platform"); Alto's expectations with regard to the design and results of its clinical trials; the reproducibility of positive clinical data seen in prior trials of CTC-501/ALTO-207; Alto's clinical and regulatory development plans for ALTO-207; the competitive landscape and potential market opportunities for ALTO-207; and Alto's anticipated cash runway. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto's actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled "Risk Factors" in Alto's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the Securities and Exchange Commission ("SEC") as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto's Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website. View source version on Contacts Investor and Media Contact: Mari Purpurainvestors@ media@
Business Wire
29-05-2025
- Health
- Business Wire
Alto Neuroscience Presents Data at the 2025 American Society of Clinical Psychopharmacology Annual Meeting Reinforcing Safety and Tolerability Profile for ALTO-300 in Major Depressive Disorder
MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Alto Neuroscience, Inc. ('Alto') (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced a presentation at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, in Scottsdale, Arizona, held May 27-30, 2025. ALTO-300, also known as agomelatine, is an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist being developed at 25mg as an adjunctive treatment in the United States for patients with MDD, characterized by an EEG biomarker. Agomelatine is an approved antidepressant medication at both 25mg and 50mg in Europe and Australia but has not been approved in the United States. In clinical studies, the 50mg dose of agomelatine was associated with low levels of reversible liver enzyme elevations, which were not associated with liver failure. In comparison to the 50mg dose of agomelatine, the 25mg dose has been shown to have similar antidepressant activity while avoiding the rates of liver function test (LFT) elevations associated with the 50mg dose. 'Our ASCP presentation continues to support the unique biomarker opportunity for patient stratification and reinforces the well-established safety and tolerability profile for ALTO-300,' said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. 'Agomelatine has been studied in thousands of patients globally and evidence from meta-analyses and real-world clinical care demonstrates the 25mg dose achieves an optimal balance of antidepressant activity without the concern of LFT elevation. These data are consistent with the positive results from our completed Phase 2a trial, and we are encouraged by the safety and tolerability profile of ALTO-300 in our ongoing Phase 2b trial in patients with major depressive disorder. Taken together, we believe the selected 25mg dose of ALTO-300 is well positioned to demonstrate clinical effects while avoiding the low LFT elevation rates associated with the 50mg dose, which typically occur early, are non-cumulative, resolve quickly, and are not associated with liver failure.' Summary of Data Presented ALTO-300 Safety and Tolerability Profile The most common adverse event observed in the completed Phase 2a trial of ALTO-300 was headache. Additionally, the Phase 2a and Phase 2b trials have involved monitoring for elevated liver enzymes (≥ 3 times the upper limit of normal), with the Phase 2b trial including a stopping rule for elevated liver enzymes. No LFT elevations ≥ 3 times the upper limit of normal were observed in the Company's 239-patient completed Phase 2a trial, and no patients have been stopped in the ongoing Phase 2b trial due to liver enzyme elevation, which remains blinded. ALTO-300 EEG Biomarker The ALTO-300 biomarker signal likely reflects increased neural noise due to elevated 5-HT2C tone and reduced dopaminergic activity. Increasing 5-HT2C activity in a preclinical rodent model or directly depleting dopamine in a healthy human volunteer study—both the oppositive mechanistic effect of ALTO-300—resulted in greater EEG irregularity, consistent with a biomarker positive profile. These data reinforce the direct link between ALTO-300 and the EEG biomarker used to identify MDD patients who are more likely to be responders to treatment. The following poster presented at ASCP 2025 is available under ' Publications ' in the platform section of Alto's website: ALTO-300 as Adjunctive Treatment for Major Depressive Disorder Supported by Mechanistic Validation of Patient Selection Biomarker and Well-Established Safety and Tolerability Profile Poster First Author: Michael Avissar, Ph.D. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto's Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto's clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X. Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as 'expects,' 'plans,' 'will' and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto's expectations about the potential benefits, activity, and effectiveness of its product candidates, biomarkers, and Precision Psychiatry Platform ('Platform'); and Alto's expectations with regard to the design and results of its clinical trials. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto's actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled 'Risk Factors' in Alto's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the Securities and Exchange Commission ('SEC') as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto's Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website.
