Alto Neuroscience, Inc.

Company at a glance

• Structure: Clinical-stage biopharmaceutical company focused on precision psychiatry.
• Mission: Redefine neuropsychiatric care by using neurobiological biomarkers to identify which patients are most likely to respond to specific medicines.
• Core approach: Precision Psychiatry Platform that combines neurobiological measurements (EEG, neurocognitive assessments, wearable data, genetics) with quantitative analytics and machine learning to discover and replicate biomarkers that predict drug response and to characterize drug effects on the brain.
• Therapeutic focus: Major depressive disorder (MDD), bipolar depression (BPD), treatment-resistant depression (TRD), schizophrenia, and Parkinson’s disease (PD).

Platform and data capabilities

• Platform inputs: Neurocognitive tests, EEG, wearable sensor data, genetic/genomic data.
• Analytics: Quantitative methods and machine learning to identify biomarker signatures and biomarker-defined responder populations.
• Practical aims: Biomarkers designed for collection in typical clinical settings to enable scalable, biomarker-guided development and potential companion diagnostics.
• Scale and data footprint: Biomarker data collected across more than 70 clinical sites from over 2,000 participants.
• Commercial aim: Platform architecture intended for deployment in real-world clinical practice with minimal clinician interpretation required.

Clinical pipeline (seven clinical-stage assets)

• ALTO-207

  • Mechanism: Fixed-dose combination of pramipexole (dopamine D3-preferring agonist) and ondansetron (5-HT3 antagonist).
  • Indication: Treatment-resistant depression (TRD).
  • Status: Acquired May 2025 from Chase Therapeutics (CTC-501). Phase 2b planned to begin in H1 2026. Company plans for potential pivotal trial after FDA feedback, targeting Phase 3 readiness by 2027 pending FDA alignment.

• ALTO-300

  • Mechanism: Agomelatine (25 mg; MT1/MT2 agonist; 5-HT2C antagonist) as adjunctive therapy.
  • Biomarker strategy: EEG biomarker signature to select biomarker-positive MDD patients; approximately 50% of MDD patients may be biomarker-eligible for this program.
  • Status: Phase 2b underway; topline data expected mid-2026.

• ALTO-100

  • Mechanism: PDE4 inhibitor with a pro-neuroplasticity approach.
  • Formulation: Transdermal to mitigate CNS-related tolerability issues seen with oral PDE4 inhibitors.
  • Indication: Primary target is bipolar depression (BPD); also studied in MDD contexts.
  • Status: Completed Phase 2b in MDD (Oct 2024 topline) but did not meet the primary endpoint in the overall MDD cohort. Ongoing Phase 2b in BPD, including a biomarker-enriched adjunctive cohort; topline data expected in 2H 2026.

• ALTO-101

  • Mechanism: Brain-penetrant PDE4 inhibitor in a transdermal formulation (partnered with MedRx for patch delivery).
  • Indication: Cognitive impairment associated with schizophrenia (CIAS).
  • Status: Phase 2 proof-of-concept trial (cross-over, dose-escalation); topline data anticipated around Q1 2026. FDA Fast Track designation granted October 2025.

• ALTO-203

  • Mechanism: Histamine H3 receptor inverse agonist.
  • Indication: MDD with elevated levels of anhedonia (biomarker-guided approach).
  • Status: Exploratory Phase 2 proof-of-concept completed June 2025; a biomarker was identified and pharmacodynamic signals observed. Further development direction to be determined.

• ALTO-202

  • Mechanism: NMDA receptor GluN2B antagonist.
  • Status: In-licensed from Cerecor; planning next clinical steps.

• ALTO-208

  • Mechanism: Fixed-dose combination of pramipexole and aprepitant (NK-1 antagonist).
  • Indication: Parkinson’s disease (PD).
  • Status: Acquired May 2025 from Chase (CTC-413); development planned around PD-related indications.

• Portfolio scope: The seven clinical-stage assets cover MDD, TRD, BPD, schizophrenia, and PD, using biomarker-driven selection and multiple delivery approaches, including transdermal PDE4 inhibitors and fixed-dose combinations.

Licensing, collaborations, and partnerships

• Stanford University: Exclusive worldwide license for Stanford patents and technology related to brain stimulation, EEG, and functional MRI for psychiatry applications (exclusive through 2029, then non-exclusive; Stanford retains non-profit rights). Agreement includes upfronts and royalties.
• Sanofi: Exclusive worldwide license to use a PDE4 inhibitor (ALTO-101) for all human therapeutic uses, including related know-how; milestone and royalty structure applies.
• Cerecor: Exclusive worldwide license to ALTO-202 (GluN2B NMDA antagonist) with co-ownership rights for certain Merck-related improvements; tiered royalties and milestone payments.
• Teva: Asset purchase of ALTO-203 and related compounds; milestones and royalties tied to development, regulatory approvals, and sales; manufacturing and commercialization obligations defined.
• Palisade: Asset transfer of ALTO-100 rights (including related Dow patent rights for manufacturing); milestones and potential royalties.
• MedRx: Joint development and license for ALTO-101 transdermal delivery; exclusive worldwide license to use MedRx’s patch technology with ALTO-101; ongoing collaboration with milestone and royalty terms.
• Wellcome Trust: Convertible grant agreement providing up to approximately $11.7 million as a convertible loan; additional draw-downs contingent on milestones; proceeds targeted to advance ALTO-100 in bipolar depression.

Intellectual property landscape

• Overall footprint: Approximately 235 patents and applications globally; 35 issued US patents and 97 issued foreign patents.
• Product-related IP: About 167 patents/patent applications specifically related to product candidates and platform IP. Patent expiries generally range from the late 2020s to the mid-2040s, subject to maintenance and term adjustments.
• Platform IP: One pending US patent application related to placebo/response prediction; licensed Stanford IP in machine learning and biomarker-based patient selection with expiry windows in the 2030s–2040s depending on jurisdiction.
• Strategy: Ongoing assessment and expansion of patent protection across composition-of-matter, method-of-use, manufacturing, and biomarker-related claims, supplemented by in-licenses and collaborations.

Commercialization status and business model

• Commercial readiness: No approved products and no product revenue to date.
• Commercial organization: No established internal commercial team; plans to build capabilities over time and pursue partnerships for non-U.S. geographies.
• Market positioning: Focus on precision psychiatry with biomarker-guided trials intended to increase probability of success and address unmet needs in MDD, TRD, BPD, schizophrenia, and PD.
• Addressable market: Company references a potential impact on over 25 million patients in the United States across its portfolio.

Financial position and liquidity

• Employees: 68 total as of December 31, 2025 (66 in the US; 2 in Australia).
• Revenue: None from product sales.
• Net losses: Approximately $63.2 million for the year ended December 31, 2025; approximately $61.4 million for 2024.
• Accumulated deficit: Approximately $201.6 million as of December 31, 2025.
• Cash position: Approximately $177.0 million in cash, cash equivalents, and restricted cash as of December 31, 2025.
• Runway: Existing resources are expected to fund operations for at least the next 12 months based on the current plan.
• Financing and leverage:
  • Amended Loan Agreement with K2 HealthVentures and others enabling up to $75.0 million in term loans; collateralized with covenants, staged drawdowns, lender conversion rights, and potentially dilutive warrants.
  • Convertible Grant Agreement with the Wellcome Trust for up to roughly $11.7 million in convertible loan funding; draws contingent on milestones with conversion and dilution implications.
  • Chase Asset Purchase Agreement (May 2025): Acquisition of ALTO-207, ALTO-208, and related assets with up to $71.5 million in milestone payments (cash and restricted stock), subject to a cap on stock issuance.
• Ongoing obligations: Multiple contingent milestone and royalty payments across licensing and collaboration agreements that could affect future cash flows and dilution.

Manufacturing and operations

• Manufacturing model: No owned manufacturing facilities; relies on third-party contract manufacturers for preclinical and clinical supply with plans for later-stage arrangements if products advance.
• Platform and tools: In-house software tools (Spectra, Altoscope, TechCheck) support biomarker data collection and analysis; software development and data oversight are ongoing.

Regulatory landscape and strategy

• U.S. pathway: NDA/505(b)(2) strategies under consideration for candidates including ALTO-207. ALTO-101 has FDA Fast Track designation.
• Companion diagnostics: Companion diagnostics are a core element for several programs. FDA discussions are anticipated around end of Phase 2 for ALTO-100 and ALTO-300 to align on biomarker-defined populations.
• International plans: The company intends to pursue foreign regulatory approvals as appropriate; foreign trials and pricing/reimbursement strategies will be important for market access.

Summary

Alto Neuroscience is developing a portfolio of biomarker-guided therapies and companion diagnostics built on a Precision Psychiatry Platform. The company has seven clinical-stage assets targeting major neuropsychiatric conditions, broad licensing and collaboration arrangements, a substantial IP footprint, and around $177 million in cash at the end of 2025. It operates with a lean team and plans to advance multiple biomarker-enabled trials while funding development through a mix of debt, convertible financing, equity, and partnerships.