Alto Buys Depression and Parkinson's Drug Portfolio for $1.75M Upfront, With $71.5M in Future Milestones

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, MB.BS, 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.