-- Acquisition of ALTO-207 targets Treatment-Resistant Depression (TRD) with a clinically-validated mechanism; Phase 2b trial on track to be initiated in the first half of 2026 --

-- External PAX-D study published in The Lancet Psychiatry demonstrated a 0.87 effect size for the core mechanism of ALTO-207; this effect represents a significantly larger effect size than current standard-of-care treatments --

-- ALTO-101 granted FDA Fast Track Designation for CIAS; Topline Phase 2 Proof-of Concept data expected around the end of 1Q 2026 --

-- Year-end cash balance of $177 million expected to fund planned operations into 2028, covering four key data readouts across Alto's precision psychiatry pipeline --

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--March 16, 2026-- 

Alto Neuroscience, Inc. ("Alto") (NYSE: ANRO), a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today reported financial results for the full year ended December 31, 2025, and highlighted recent progress across its pipeline of clinical-stage product candidates.

"Alto enters 2026 with a very strong clinical and financial foundation," said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. "The acquisition of ALTO-207 is a potential game-changer for the millions of patients who fail to respond to current depression therapies. We believe the Lancet-published PAX-D study provides robust, independent validation of our approach, and we are moving ALTO-207 into a potentially pivotal Phase 2b trial with high conviction. Our $177 million cash balance puts us in an excellent position to reach the finish line on four major data readouts, providing shareholders with multiple value-inflection points over the next 2 years."

Recent Business Highlights

   --  Acquisition and Accelerated Development of ALTO-207 for TRD: In June 
      2025, Alto acquired ALTO-207, a fixed-dose combination of pramipexole (a 
      dopamine D3/D2 agonist) and ondansetron (an antiemetic 5-HT3 receptor 
      antagonist). ALTO-207 is designed to overcome historic tolerability 
      barriers associated with dopamine agonists, potentially unlocking a rapid 
      and robust antidepressant effect for patients in need. 
 
          --  Following a successful FDA meeting and a $50 million private 
             placement financing $(PIPE)$ in October 2025, Alto has accelerated 
             the program's development. The Company expects to initiate a 
             potentially pivotal Phase 2b trial in the first half of 2026 and a 
             Phase 3 trial by early 2027. 
 
          --  In January 2026, the Company announced the issuance of a new 
             method-of-treatment patent for ALTO-207, which together with its 
             broader estate of issued and pending patents, Alto expects to have 
             patent coverage of ALTO-207 through at least the mid 2040's. 
 
          --  The planned Phase 2b trial of ALTO-207 will be a randomized, 
             double-blind, placebo-controlled study evaluating ALTO-207 as an 
             adjunctive treatment in approximately 178 adults with 
             treatment-resistant depression (TRD). Eligible patients will have 
             experienced two to five prior treatment failures and have a MADRS 
             score >=25, and will remain on their baseline antidepressant 
             medication. Participants will be randomized 1:1 to receive 
             ALTO-207 or placebo during an eight-week double-blind treatment 
             period, which includes dose titration to a target total daily dose 
             of 3.2mg pramipexole/15mg ondansetron. The study will be conducted 
             at clinical sites in the U.S. and U.K. The primary endpoint is 
             change from baseline in MADRS. The Company expects to report 
             topline data from the trial in the second half of 2027. 
 
 
   --  PAX-D Study Validates Pramipexole in TRD: The strategic acquisition of 
      ALTO-207 was guided by the independent PAX-D study, the results of which 
      were published in The Lancet Psychiatry in June 2025. The study 
      demonstrated that pramipexole augmentation drove a large, statistically 
      significant reduction in depressive symptoms (Cohen's d=0.87) relative to 
      placebo at 12 weeks in patients with TRD. This represents an effect size 
      more than two times larger than what has historically been demonstrated 
      with standard-of-care treatments in depression or TRD. However, the study 
      also highlighted a high rate of adverse effects (nausea) that hinder 
      pramipexole's standard clinical adoption--a barrier ALTO-207 is 
      explicitly designed to overcome. 
 
          --  Alto recently conducted a meta-analysis across randomized 
             studies of pramipexole for depression. The analysis highlights the 
             large effect size observed on depression symptoms with pramipexole 
             and a clear dose-response relationship. The analysis, including 
             all pramipexole doses studied in randomized depression trials, 
             resulted in a meta-analytic Hedges' g effect size of 0.64 (p<0.001 
             [95% CI 0.41 - 0.86]) across all doses studied. The meta-analysis 
             also revealed a significant dose-response relationship (p=0.027), 
             showing that higher doses of pramipexole result in larger effects 
             on depression symptoms. 
 
                 --  See here for an interactive meta-analysis of pramipexole 
                    in depression. 
 
 
 
 
   --  ALTO-101 in Cognitive Impairment Associated with Schizophrenia $(CIAS)$: 
      In October 2025, the FDA granted Fast Track Designation to ALTO-101. In 
      February 2026, Alto announced the completion of enrollment in the ongoing 
      Phase 2 proof-of-concept (POC) trial. The Company expects to report 
      topline data from the trial around the end of the first quarter of 2026. 
 
          --  The primary endpoint in the study is theta-band inter-trial 
             coherence (ITC), an EEG measure strongly correlated with cognitive 
             performance, measured during an auditory oddball paradigm. 
             Additional EEG endpoints include resting-state theta power, 
             mismatch negativity, and auditory steady-state response. Cognitive 
             performance will be assessed using select domains of the MATRICS 
             Consensus Cognitive Battery (MCCB) and a computerized measure of 
             processing speed. 
 
          --  A recent blinded pharmacokinetic, or PK, analysis from the first 
             cohort of patients showed 100% of samples evaluated qualified as 
             PK positive. 
 
 
   --  ALTO-300 and ALTO-100 Ongoing Phase 2b Trials: Enrollment continues in 
      the Phase 2b trial of ALTO-300 in Major Depressive Disorder (MDD), with 
      topline data expected in mid-2026. The Phase 2b trial of ALTO-100 in 
      Bipolar Depression (BPD) is also ongoing, with topline data anticipated 
      in the second half of 2026. 

Upcoming Milestones

Near-Term Expected Milestones

   --  Approximately end of 1Q 2026 -- ALTO-101 POC CIAS trial topline data 
 
   --  1H 2026 -- ALTO-207 Phase 2b TRD trial initiation 
 
   --  Mid-2026 -- ALTO-300 Phase 2b MDD trial topline data 
 
   --  2H 2026 -- ALTO-100 Phase 2b BPD trial topline data 
 
   --  Early 2027 -- ALTO-207 Phase 3 TRD trial initiation 

Full Year 2025 Financial Highlights

Cash Position: As of December 31, 2025, the Company had cash, cash equivalents, and restricted cash of approximately $177 million, compared to approximately $169 million in cash, cash equivalents, and restricted cash as of December 31, 2024.

The Company expects its cash balance to support planned operations into 2028.

R&D Expenses: Research and development expenses for the full year ended December 31, 2025 were $45.6 million, as compared to $47.0 million for the same period in 2024. The decrease was primarily attributable to the completion of our Phase 2b clinical study for ALTO-100 in 2024 and the completion of our proof-of-concept study for ALTO-203, partially offset by increases related to the costs of our ongoing trials of ALTO-101 and ALTO-100.

G&A Expenses: General and administrative expenses for the full year ended December 31, 2025 were $20.7 million, as compared to $21.6 million for the same period in 2024.

Net Loss: The Company incurred a net loss of $63.2 million for the full year ended December 31, 2025, as compared to $61.4 million for the year ended December 31, 2024.

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$(TM)$ 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.

Forward-Looking Statements

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March 16, 2026 06:03 ET (10:03 GMT)