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
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 www.altoneuroscience.com 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.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Business Wire
26 minutes ago
- Business Wire
MedX Health Corp. Names Meghan Geary as Senior Vice President of Operations
MISSISSAUGA, Ontario--(BUSINESS WIRE)--MedX Health Corp. ('MedX' or the 'Company') (TSXV: MDX), the global leader in teledermatology solutions, confirms the appointment of Meghan Geary as the Company's Senior Vice President of Operations, effective immediately. With over 10 years experience in building scalable programs across SaaS and high-growth healthcare companies, Geary will oversee strategic operations, drive organization performance, and support MedX's continued growth trajectory. "I'm excited to join MedX at such a pivotal stage of its journey," said Geary. "Throughout my career, I've focused on scaling programs that streamline processes and promote cross-functional alignment. I look forward to collaborating with the MedX team to optimize operations and ensure the Company is positioned for long-term success." The Company's CEO, John Gevisser added: 'Meghan brings formidable experience to MedX at a time when we are scaling operations across different markets. Having previously worked closely with her, I understand what a vital asset to our team she is. Her ability to lead strategic programs, adjust and direct processes and improve organizational performance will play a central role in our next phase of growth. Meghan critically understands that our deep and dynamic image store is central to our AI and SaaS strategy.' About MedX Health Corp. MedX Health Corp., headquartered in Ontario, Canada, is a leader in non-invasive skin assessment and teledermatology. Its proprietary SIAscopy ® technology, integrated into the DermSecure ® platform, enables pain-free, accurate imaging of skin lesions for rapid dermatologist review. These products are cleared for use in 38 countries including by Health Canada, the U.S. Food and Drug Administration ('FDA'), the Therapeutic Goods Administration and Conformité Européenne, for use in Canada, the U.S., Australia, New Zealand, the United Kingdom, the European Union and Turkey. MedX's advanced telemedicine platform enables healthcare professionals to quickly and accurately assess suspicious moles, lesions, and other skin conditions through its proprietary imaging technology, SIAscopy ®, and its secure, cloud-based patient management system, DermSecure ®. SIAscopy® is the only technology capable of capturing five high-resolution images, including four spectrophotometric scans that penetrate 2mm below the skin's surface. Visit: https// This Media Release may contain forward-looking statements, which reflect the Company's current expectations regarding future events. The forward-looking statements involve risks and uncertainties.
Business Wire
an hour ago
- Business Wire
Modivcare Enters into Comprehensive Restructuring Agreement to Strengthen its Future, Reduce Debt and Inject Capital
DENVER--(BUSINESS WIRE)--Modivcare Inc. (the 'Company' or 'Modivcare') (Nasdaq: MODV), a technology-enabled healthcare services company providing a platform of integrated supportive care solutions focused on improving health outcomes, today announced that it has taken necessary and decisive action intended to strengthen its financial foundation while continuing to provide access to care, reduce costs, and improve outcomes for clients and members nationwide. Modivcare has filed for voluntary Chapter 11 protection in the U.S. Bankruptcy Court for the Southern District of Texas to implement a comprehensive restructuring transaction with the support of a supermajority of its key stakeholders. Through this process, Modivcare intends to build a stronger, sustainable organization, positioned for growth and well-equipped to meet the critical needs of members across its non-emergency medical transportation, personal care services and remote patient monitoring service lines. 'Modivcare sits at the center of the preventive healthcare ecosystem,' said Heath Sampson, Chief Executive Officer and President of Modivcare. 'This recapitalization strengthens our balance sheet and allows Modivcare to accelerate our investment in innovation by combining technology and data with high-touch member engagement. As the connector to care, our seamlessly connected platform improves access, quality and cost for payors, providers and facilities, while positioning us to lead the future of coordinated care.' More than 90% of First Lien Lenders and more than 70% of Second Lien Lenders have entered into a Restructuring Support Agreement ('RSA') with the Company. Those lenders have committed to support the Company throughout this process and have agreed to provide $100 million in 'debtor-in-possession' ('DIP') financing to finance the restructuring process and to support ongoing operations during this expedited bankruptcy process. Upon the closing of the DIP loan, Modivcare will have liquidity in excess of $100 million. The restructuring will reduce the Company's total outstanding funded debt obligations by approximately $1.1 billion (which is more than 85% of its outstanding funded debt obligations) and will meaningfully reduce the Company's annual cash interest and transition ownership to a group of seasoned and well-funded investors who are committed to Modivcare's success. All of Modivcare's service lines will continue to operate in the ordinary course, and we expect no interruption or change in access to care and a continued focus on operational excellence. Modivcare intends to close this transaction quickly by exiting the restructuring process early in the fourth quarter of 2025. Modivcare remains committed to providing excellent service to clients and their members. The Company has filed customary motions that, once approved, will allow Modivcare to meet obligations to clients and critical vendors, including transportation providers, and pay employee wages and benefits as usual. For more information about the Company's Chapter 11 case, including claims information, please visit or contact Verita, the Company's noticing and claims agent, at +1 (888) 733-1521 for U.S. and Canada or +1 (310) 751-2636 for international. Modivcare is advised by Latham & Watkins LLP, Hunton Andrews Kurth LLP, Moelis & Company LLC, and FTI Consulting. The First Lien Agent, the First Lien Lenders and the Second Lien Noteholders executing the RSA are advised by Paul Hastings LLP and Lazard. Cautionary Note Regarding Forward-Looking Statements Statements contained in this release constitute 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are predictive in nature and are identified generally by the use of the terms 'intended', 'expected', 'estimates', 'will', and 'anticipates', and similar words or expressions indicating possible future expectations, events or actions. Forward-looking statements include statements regarding the Company's expectation about its ability to continue operating its business, fulfill its mission, make payments and meet obligations, and the Company's ability to implement the restructuring pursuant to the Chapter 11 cases, including the timetable of completing such transaction, if at all. Forward-looking statements are based on current expectations, assumptions, estimates and projections about the Company's business and its industry, and are not guarantees of future performance. These statements are subject to a number of known and unknown risks, uncertainties and other factors, many of which are beyond the Company's ability to control or predict, which may cause actual events to be materially different from those expressed or implied herein. The Company has provided additional information about the risks facing its business and the Company in its most recent annual report on Form 10-K, and in its subsequent periodic and current reports on Forms 10-Q and 8-K, filed by it with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date the statements were made and are expressly qualified in their entirety by the cautionary statements set forth herein and in the periodic and current reports filed with the Securities and Exchange Commission identified above, which you should read in their entirety before making an investment decision with respect to the Company's securities. The Company undertakes no obligation to update or revise any forward-looking statements contained in this report, whether as a result of new information, future events or otherwise, except as required by applicable law. About Modivcare Modivcare Inc. ("Modivcare" or the "Company") is a technology-enabled healthcare services company that provides a suite of integrated supportive care solutions for public and private payors and their members. The Company's value-based solutions address the social determinants of health (SDoH) by connecting members to essential care services. By doing so, Modivcare helps health plans manage risks, reduce costs, and improve health outcomes. Modivcare is a provider of non-emergency medical transportation (NEMT), personal care services (PCS), and remote patient monitoring solutions (RPM). To learn more about Modivcare, please visit
Business Wire
4 hours ago
- Business Wire
New England Journal of Medicine (NEJM) to Publish Results From Savara's Pivotal Phase 3 IMPALA-2 Clinical Trial in Autoimmune Pulmonary Alveolar Proteinosis (Autoimmune PAP)
LANGHORNE, Pa.--(BUSINESS WIRE)-- Savara Inc. (Nasdaq: SVRA) (the Company), a clinical stage biopharmaceutical company focused on rare respiratory diseases, announced that the results from the Phase 3 IMPALA-2 clinical trial will be published online in NEJM. The manuscript, titled 'A Phase 3 Trial of Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis' Following the online publication in NEJM, the manuscript will be available on the Congresses & Publications page of the Company's corporate website. 'IMPALA-2, the largest and longest Phase 3 clinical trial conducted in patients with autoimmune PAP, demonstrated that 48 weeks of once daily administration of inhaled molgramostim addresses the underlying pathophysiology of this chronic rare lung disease,' said Bruce Trapnell, M.D., Professor of Medicine and Pediatrics, University of Cincinnati College of Medicine and Lead Clinical Investigator of the IMPALA-2 trial. 'Treatment with molgramostim improved the cardinal manifestations of autoimmune PAP, namely it reduced pulmonary surfactant burden and improved pulmonary gas transfer, respiratory health-related quality of life, and patient functionality. Additionally, molgramostim was well tolerated with no notable safety concerns.' IMPALA-2 achieved statistical significance on its primary endpoint, change from baseline in the hemoglobin-adjusted percent predicted diffusing capacity of the lungs for carbon monoxide (DLco%) at Week 24. Molgramostim significantly improved pulmonary gas transfer as measured by DLco% at Week 24 compared with placebo (9.8% vs. 3.8%; estimated treatment difference, 6.0%; P<0.001 by comparison of least-squares means [LSMs]). The beneficial effect of molgramostim on pulmonary gas transfer was maintained to Week 48 as shown by the difference in LSM change from baseline in DLco% at Week 48 between molgramostim and placebo groups (11.6% vs. 4.7%; estimated treatment difference, 6.9%; P<0.001). The mean improvements in DLco% from baseline for molgramostim (9.8% at Week 24 and 11.6% at Week 48) are similar to the minimal clinically meaningful difference (MCID) in DLco% of 10% reported for pulmonary fibrosis. 1 Molgramostim improved respiratory health-related quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ) Total and Activity scores. The magnitude of LSM reduction from baseline in SGRQ Total score was significantly greater in the molgramostim group than placebo at Week 24 (-11.5 points vs. -4.9 points, estimated difference, -6.6 points; P=0.007) and remained numerically greater at Week 48 (-10.7 points vs. -5.9 points, estimated difference, -4.9 points [95% confidence interval, -10.8, 1.0]). The LSM change from baseline in SGRQ Activity score was greater for molgramostim compared with placebo at Week 24 (-13.0 points vs. -5.2 points, estimated difference, -7.8 points [95% confidence interval, -14.1, -1.5]) and at Week 48 (-13.4 vs. -7.4 points, estimated difference, -6.0 points [95% confidence interval, -13.6, 1.6]). Molgramostim improved patient function as measured by exercise capacity (expressed as peak metabolic equivalents [METs]). A MET is a unit of resting oxygen uptake which measures energy expenditure. The LSM change from baseline in peak-METs was greater at Week 48 for molgramostim than placebo (1.1 vs. 0.6; estimated treatment difference, 0.6; [95% confidence interval, 0.1, 1.0]). Peak-METs is a clinically useful unit of measure reflecting exercise capacity, prognosis, and mortality in cardiovascular disease for which a 0.5-MET increase comprises a clinically useful measure of rehabilitation. 2 Using the treadmill test in IMPALA-2, the LSM change in peak-METs from baseline to Week 48 was 1.1 in molgramostim-treated patients and the between-group difference observed at Week 48 was 0.6 peak-METs. Molgramostim reduced surfactant burden as measured by ground glass opacity (GGO) score, an exploratory endpoint in IMPALA-2; GGO scores were determined by two blinded radiologists from a chest CT scan, with scores ranging from 0 to 15 (higher scores are worse). The mean reduction from baseline in GGO score was greater in the molgramostim group than the placebo group at Week 24 (-2.1 vs -1.1). Further, the number of patients who received ≥1 whole lung lavage as rescue therapy during the double-blind intervention period was lower with molgramostim than placebo (6 [7%] vs. 11 [13%]). In IMPALA-2, molgramostim was well tolerated. Most treatment-emergent adverse events (AEs) were mild or moderate, and few led to discontinuation, with 98% of patients in the molgramostim group and 96% of patients in the placebo group completing the 48-week double-blind period on treatment. About IMPALA-2 IMPALA-2 was a global, pivotal, Phase 3, 48-week, randomized, double-blind, placebo-controlled clinical trial designed to compare the efficacy and safety of molgramostim 300 mcg self-administered once daily by inhalation with matching placebo in patients with autoimmune PAP. The trial was conducted at 43 clinical trial sites across 16 countries, including the U.S., Canada, Japan, South Korea, Australia, and countries in Europe, including Turkey. The primary efficacy assessment was hemoglobin-adjusted percent predicted diffusing capacity of the lungs for carbon monoxide (DLco%), a gas transfer measure, and the primary endpoint was change from baseline to Week 24 in percent predicted DLco%, with a secondary endpoint of change from baseline to Week 48 in percent predicted DLco%. Three additional secondary efficacy variables evaluated clinical measures of patient benefit: St. George's Respiratory Questionnaire (SGRQ) Total score, SGRQ Activity score, and exercise capacity using a treadmill test, with each endpoint measured at Weeks 24 and 48. The primary time point for efficacy assessments was at Week 24; however, efficacy was assessed through Week 48 to evaluate durability of effect. Safety was assessed through Week 48. All patients who completed the 48-week double-blind treatment period continued into a 96-week open-label period during which molgramostim 300 mcg is administered once daily. Autoimmune PAP is a rare lung disease characterized by the abnormal build-up of surfactant in the alveoli of the lungs. Surfactant consists of proteins and lipids and is an important physiological substance that lines the alveoli to prevent them from collapsing. In a healthy lung, excess surfactant is cleared and digested by immune cells called alveolar macrophages. Alveolar macrophages need to be stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) to function properly in clearing surfactant, but in autoimmune PAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering macrophages unable to adequately clear surfactant. As a result, an excess of surfactant accumulates in the alveoli, causing impaired gas transfer, resulting in clinical symptoms of shortness of breath, often with cough and frequent fatigue. Patients may also experience episodes of fever, chest pain, or coughing up blood, especially if secondary infection develops. In the long term, the disease can lead to serious complications, including lung fibrosis and the need for a lung transplant. About Savara Savara is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, molgramostim inhalation solution (molgramostim), is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (autoimmune PAP). Molgramostim is delivered via an investigational eFlow® Nebulizer System (PARI Pharma GmbH) specifically developed for inhalation of a large molecule. Our management team has significant experience in rare respiratory diseases and pulmonary medicine, identifying unmet needs, and effectively advancing product candidates to approval and commercialization. More information can be found at and LinkedIn. 1 Raghu G, et al. Am J Respir Crit Care Med 2022;205:e18-e47. 2 Ross R, et al. Circulation 2016;134:e653-e99; Grace SL, et al. Can J Cardiol 2014;30:945-8; Kehler DS, et al. J Cardiopulm Rehabil Prev 2017;37:250-6.
