Alto Neuroscience Presents Phase 2a Data for ALTO-207 in Major Depressive Disorder at SOBP Annual Meeting

— Randomized, placebo-controlled, Phase 2a trial demonstrated robust, statistically significant antidepressant effects of ALTO-207 and favorable tolerability; supporting development of ALTO-207 in ~7 million patient treatment-resistant depression market —

— Phase 2b Ongoing with topline data expected in 2H 2027 —

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--$anro #cns--Alto Neuroscience, Inc. (NYSE: ANRO), a clinical-stage biopharmaceutical company focused on precision medicines for neuropsychiatric disorders, today announced the presentation of data from a randomized, single-blind, placebo-controlled Phase 2a trial of ALTO-207 (formerly CTC-501) in patients with Major Depressive Disorder (MDD). The data were presented in a poster session at the 2026 Annual Meeting of the Society of Biological Psychiatry (SOBP).

ALTO-207 is a fixed-dose combination of pramipexole, a dopamine D3/D2 agonist with antidepressant activity demonstrated across multiple prior studies, and ondansetron, a 5-HT3 antagonist anti-emetic. The novel, patent-protected combination is designed to enable faster titration to higher pramipexole doses by reducing dose-limiting nausea and vomiting — the key barrier that has historically prevented patients from reaching therapeutically effective doses of pramipexole in clinical practice.

Presentation Highlights; Phase 2a Trial Design and Results

The trial enrolled 32 adults with MDD (mean age 42.8; 47% female; baseline MADRS 28.5). Participants were titrated to a maximum of 5 mg/day pramipexole, with ondansetron fixed at 16 mg/day, followed by an outpatient maintenance period. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression – Severity scale (CGI-S), analyzed by Mixed Models for Repeated Measures (MMRM).

• Titration: Participants reached a mean pramipexole dose of 4.1 mg within 8 days; 60% tolerated the maximum 5 mg dose by day 12.
• MADRS: ALTO-207 showed a statistically significant reduction in depressive symptoms versus placebo at Week 6 (Cohen's d=1.67, p=0.0004) and Week 8 (d=1.1, p=0.025).
• CGI-S: A statistically significant reduction in illness severity was observed at Week 6 (d=1.27, p=0.007) and Week 8 (d=1.0, p=0.04).
• Tolerability: No participants in the ALTO-207 arm discontinued due to adverse events during the maintenance phase. Treatment-related nausea was reported in 15% of ALTO-207 participants during the post-titration maintenance period. The titration schedule being employed in the ongoing Phase 2b trial has been modified with the goal of further improving tolerability.

"These Phase 2a results validate the core premise of ALTO-207: that pairing pramipexole with ondansetron allows patients to reach doses that have been associated with greater antidepressant effect, but are rarely achieved with pramipexole alone,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “The effect sizes observed, and the durability of response through Week 8, together with the external PAX-D positive results, gave us the confidence to advance ALTO-207 into a potentially registrational Phase 2b trial in treatment-resistant depression. We believe the direct dopaminergic mechanism of ALTO-207 addresses a gap that existing antidepressants do not."

About ALTO-207

ALTO-207 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 treatment resistant depression.

In 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.

About Treatment-Resistant Depression (TRD)

Treatment-resistant depression (TRD) is a serious form of major depressive disorder (MDD), typically defined as inadequate response to at least two prior antidepressant treatments of adequate dose and duration. Despite the availability of multiple therapies, approximately one-third of patients with MDD do not achieve sufficient symptom relief with standard treatments.

MDD affects approximately 21 million adults in the United States each year, suggesting that an estimated 6–7 million individuals may suffer from TRD. Patients with TRD often experience persistent, recurrent symptoms, increased risk of hospitalization and suicide, and significant impairment in daily functioning.

TRD represents a substantial unmet medical need and a disproportionate share of the overall economic burden of depression, driven by higher healthcare utilization, reduced productivity, and long-term disability. Current treatment approaches are frequently characterized by a trial-and-error process, delayed onset of action, substantial side effect burden, and limited rates of sustained response.

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, schizophrenia, and other mental health conditions. For more information, visit www.altoneuroscience.com or follow Alto on X.

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