\nAlto Neuroscience, Inc. (\u201cAlto\u201d) (NYSE: ANRO) today highlighted the publication in Nature Medicine<\/i> of PRIME-PRAXOL<\/a>, an independent, randomized, double-blind, placebo-controlled trial of the dopamine agonist pramipexole in patients with mood disorders and clinically significant anhedonia. The study was conducted and independently funded by investigators at Lund University, Sweden.<\/p>\n
\nAdults with elevated baseline anhedonia symptoms with a diagnosis of major depressive disorder, dysthymia (chronic low mood, but not meeting MDD diagnostic criteria), or bipolar depression were randomized to flexible-dose pramipexole or placebo, added to ongoing treatment, for nine weeks, followed by a six-month open-label extension period. On the primary endpoint, pramipexole reduced anhedonia significantly more than placebo on the Snaith\u2013Hamilton Pleasure Scale (mean difference \u22124.04; 95% CI \u22126.89 to \u22121.18; p=0.006; Hedges\u2019 g=0.62 – Hedges\u2019 g is a standardized measure of treatment effect similar to Cohen\u2019s D), with significant improvements on independent measures of anhedonia (DARS; p=0.008) and apathy (AES-S; p<0.001) with improvements maintained through a six-month open-label treatment period.<\/p>\n
\nImportantly, the publication also included a post-hoc analysis which found that a diagnosis of MDD, compared to the milder affective condition of dysthymia, showed a significant association with a greater change in SHAPS at week 9 in a regression analysis (p=0.038). In an analysis not published in the Nature Medicine piece, the MDD subgroup demonstrated a significantly larger effect on SHAPS at week 9 (Hedges\u2019 g=0.99) and a significant effect on the Hamilton Depression Rating Scale (HDRS-6) (Hedges\u2019 g=0.64).<\/p>\n
\n\u201cAnhedonia is among the most disabling yet poorly addressed dimensions of depression, and it is the domain dopaminergic mechanisms are perhaps best positioned to address,\u201d said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. \u201cThese Nature Medicine<\/i> results add independent, peer-reviewed high-profile evidence \u2014 alongside PAX-D in The Lancet Psychiatry<\/i> \u2014 for the effects of pramipexole, the active dopaminergic component of ALTO-207. Notably, the high nausea rate in this trial illustrates the precise tolerability limitation ALTO-207 is engineered to overcome \u2014 aiming to unlock this promising mechanism for a broader patient population. We are very encouraged by the results from this trial, further strengthening the scientific foundation for ALTO-207 as we advance our potentially pivotal Phase 2b trial in treatment-resistant depression.\u201d<\/p>\n
\nConsistent with prior studies, adverse events were common in the pramipexole arm despite a slow titration schedule \u2014 including nausea in roughly 60% of participants, along with sleep disturbance, dizziness, fatigue, and anxiety \u2014 reflecting the dose-limiting tolerability that has long constrained pramipexole\u2019s use. ALTO-207 pairs pramipexole with the antiemetic ondansetron specifically aimed at mitigating these effects and enabling faster titration to therapeutic doses.<\/p>\n
\n\u201cConventional antidepressants have little effect on the brain\u2019s reward systems, leaving depressed patients with anhedonia having marked symptoms. With this study, the Lund group adds to the other recent work demonstrating that pramipexole greatly reduces this anhedonic burden,\u201d said Alan Schatzberg, MD, Kenneth T. Norris Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine. \u201cWhat stands out in this study is the consistency of the findings \u2014 pramipexole improved both the consummatory and motivational dimensions of anhedonia, on multiple independent scales, and with good durability. Matching a dopaminergic treatment to patients defined by anhedonia, and potentially related reward-circuit dysfunction, is the kind of mechanism-led approach the field needs.\u201d<\/p>\n
\nThe published findings across the PRIME-PRAXOL study are consistent with the broader evidence supporting ALTO-207, including PAX-D (Cohen\u2019s d=0.87 versus placebo at 12 weeks in treatment-resistant depression) and a meta-analysis of pramipexole in depression (Hedges\u2019 g=0.64).<\/p>\n
About ALTO-207<\/b><\/p>\n
\nALTO-207 is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3\/D2 agonist, approved for the treatment of Parkinson\u2019s 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 treatment resistant depression.<\/p>\n
\nIn a randomized, placebo-controlled Phase 2a clinical trial evaluating ALTO-207 in 32 patients with depression ALTO-207 met primary and secondary endpoints demonstrating significantly greater improvements on MADRS compared to placebo. Patients randomized to receive ALTO-207 reached a mean dose of 4.1mg per day. ALTO-207 was well tolerated in the maintenance period of the study with an adverse event rate similar to placebo.<\/p>\n
About Alto Neuroscience<\/b><\/p>\n
\nAlto 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\u2019s Precision Psychiatry Platform\u2122 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\u2019s clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression, schizophrenia, and other mental health conditions. For more information, visit www.altoneuroscience.com<\/a> or follow Alto on X<\/a>.<\/p>\n Forward-Looking Statements<\/b><\/p>\n 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 \u201caims,\u201d \u201canticipates,\u201d \u201cbelieves,\u201d \u201ccould,\u201d \u201cestimates,\u201d \u201cexpects,\u201d \u201cforecasts,\u201d \u201cgoal,\u201d \u201cintends,\u201d \u201clook forward,\u201d \u201cmay,\u201d \u201cplans,\u201d \u201cpossible,\u201d \u201cpotential,\u201d \u201cseeks,\u201d \u201cwill,\u201d 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\u2019s expectations about the potential benefits, activity, effectiveness, tolerability and safety of its product candidates and Precision Psychiatry Platform (\u201cPlatform\u201d); statements regarding Alto\u2019s expectations for the design, timing, and results of its Phase 2b and planned Phase 3 trials of ALTO-207; Alto\u2019s expectations with regard to the general design and results of its research and development programs and clinical trials, including the timing of enrollment and the timing and availability of data from such trials; Alto\u2019s clinical development plans for its product candidates, including the timing or likelihood of approvals for its product candidates; Alto\u2019s business strategy, financial position, including anticipated cash runway, and the sufficiency of its financial resources to fund its operations through expected milestones; and other statements that are not historical fact. 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 development of Alto\u2019s product candidates; availability and timing of results from clinical trials; the risk that clinical trials may have unsatisfactory outcomes; the risk that Alto\u2019s projections regarding its financial position and expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Alto\u2019s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled \u201cRisk Factors\u201d in Alto\u2019s Annual Report on Form 10-K for the fiscal year ended December 31, 2025 filed with the Securities and Exchange Commission (\u201cSEC\u201d) 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.<\/i><\/p>\n Availability of Information on Alto\u2019s Website<\/b><\/p>\n \nAlto routinely uses its investor relations website<\/a> 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.<\/p>\n View source version on businesswire.com: <\/span>https:\/\/www.businesswire.com\/news\/home\/20260615604254\/en\/<\/a><\/span><\/p>\n Investor and Media Contact: KEYWORDS:<\/b> Europe Sweden United States North America California<\/p>\n INDUSTRY KEYWORDS:<\/b> Biotechnology Health Neurology Pharmaceutical Other Science University Publishing Mental Health Research Education Communications Science Clinical Trials Nursing<\/p>\n<\/p>\n
\n<\/b>
Nick Smith
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investors@altoneuroscience.com
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media@altoneuroscience.com<\/a><\/p>\n
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