Latest news with #Agomelatine
Business Wire
6 days ago
- 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.
Business Wire
24-04-2025
- Health
- Business Wire
Seaport Therapeutics Presents New Preclinical Data on SPT-320 (Glyph Agomelatine) at the Society of Biological Psychiatry (SOBP) Annual Meeting
BOSTON--(BUSINESS WIRE)-- Seaport Therapeutics, a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the presentation of new preclinical data from SPT-320 at the Society of Biological Psychiatry (SOBP) Annual Meeting held on April 24-26 in Toronto, Canada. SPT-320 is a novel oral prodrug of agomelatine in development for the treatment of generalized anxiety disorder (GAD). The new findings demonstrate the potential of SPT-320 to deliver therapeutically relevant levels of agomelatine at lower doses, minimizing the impact on the liver, and addressing a key limitation that has previously held back agomelatine's development in GAD. Agomelatine, a clinically validated melatonin receptor agonist and serotonin 2C receptor antagonist, is an effective anxiolytic and antidepressant approved for the treatment of GAD in Australia and major depressive disorder (MDD) in Australia and the European Union (EU). In GAD, agomelatine has demonstrated statistically significant separation from placebo in four out of four third-party placebo-controlled studies and has better efficacy and tolerability – including reduced risk of abuse potential, sexual dysfunction, and weight gain – than standard of care drugs, like benzodiazepines or selective serotonin reuptake inhibitors (SSRIs). However, since over 90 percent of unmodified agomelatine is lost to first-pass liver metabolism, its use has been limited by dose-dependent liver enzyme elevations and the need for frequent liver monitoring. Using Seaport's proprietary Glyph™ platform, SPT-320 is designed to overcome this limitation by shifting absorption toward the intestinal lymphatics, avoiding first-pass metabolism, and increasing systemic exposure of agomelatine. In newly presented data from a series of preclinical proof-of-concept studies, SPT-320 exhibited enhanced lymphatic absorption and provided significantly higher systemic exposures of agomelatine compared to agomelatine alone. Specifically, oral dosing of SPT-320 resulted in over 50 percent of agomelatine being transported through the mesenteric lymphatics versus less than one percent for orally dosed agomelatine alone. The data also show that the oral dosing of SPT-320 increased plasma exposure of agomelatine by over 10-fold versus agomelatine alone, which would allow for a reduced dose, potentially eliminating liver enzyme elevations. 'We demonstrate, for the first time, that SPT-320 has the potential to deliver therapeutically relevant levels of agomelatine with a substantially lower dose, which could significantly reduce the impact on the liver while preserving the validated efficacy of agomelatine,' said Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at Seaport Therapeutics. 'These positive results further validate our Glyph prodrug platform and support initiating clinical development of SPT-320.' The successful validation of SPT-320's pharmacological profile in preclinical models supports Seaport's progression into Phase 1 trials to further evaluate the safety, tolerability, and pharmacokinetics of SPT-320. About SPT-320 SPT-320 is a novel oral prodrug of agomelatine that has the potential to be the first new treatment for generalized anxiety disorder (GAD) in decades. Using the Glyph™ platform, SPT-320 was designed to bypass first-pass liver metabolism in order to lower the dose, reduce liver exposure, and reduce or eliminate the need for liver enzyme monitoring. Agomelatine is a clinically validated anxiolytic and antidepressant approved for GAD in Australia and major depressive disorder (MDD) in Australia and the European Union (EU). The use of agomelatine has been limited by high first-pass liver metabolism resulting in liver enzyme elevations in some patients and frequent, burdensome liver enzyme monitoring requirements. About the Glyph™ Platform Glyph is Seaport's proprietary technology platform which uses the lymphatic system to enable and enhance the oral administration of drugs. With the Glyph platform, drugs are absorbed like dietary fats through the intestinal lymphatic system and transported into circulation. The Glyph platform has the potential to be widely applied to many therapeutic molecules that have high first-pass metabolism leading to low bioavailability and/or side effects, including liver enzyme elevations or hepatotoxicity. For each program, Seaport uses Glyph to create sets of prodrugs with differentiated profiles, including lymphatic transport and conversion characteristics, as potential candidates to advance into preclinical and clinical proof-of-concept studies. Seaport exclusively licensed this technology from Monash University based on the pioneering research of the Porter Research Group. Advanced initially at PureTech Health and now at Seaport, Glyph has been applied to create therapeutic candidates for the Company's pipeline resulting in new intellectual property, including composition of matter. The group and its collaborators have published research in Nature Metabolism, Frontiers in Pharmacology, Journal of Controlled Release and Molecular Pharmaceutics supporting the Glyph platform's capabilities. See Glyph in action here. About Seaport Therapeutics Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and is guided by an extensive network of renowned scientists, clinicians, and key opinion leaders. For more information, please visit
