Alto Neuroscience's biomarker bet: ALTO-100 fails, ALTO-300 interim passes

Clinical-stage biopharma developing precision medicines for depression, PTSD, schizophrenia and other neuropsychiatric conditions, using its Precision Psychiatry Platform (EEG, neurocognitive tests, wearables) to pick patients for each drug's trials.

That EEG and cognitive biomarkers can predict which patient responds to which depression drug, so trials enroll biomarker-matched patients instead of everyone.

Seed $8M plus Series A $32M (2021, Apeiron-led); IPO Feb 2024: 8.04M shares at $16, about $128.6M gross; ~$168M cash at 2024 year-end (per Feb 2025 release).

Founded in 2019 by Stanford psychiatry professor Amit Etkin with Dan Segal and Wei Wu, Alto emerged from stealth in October 2021 with $40M ($8M seed plus a $32M Series A led by Apeiron) and a platform built on Etkin's brain-imaging research showing drug response could be predicted biologically. Its first Phase 2b readout was ALTO-100 in major depressive disorder (MDD).

Alto went public in February 2024, pricing an upsized 8.04M-share IPO at $16 for about $128.6M gross on the NYSE under ANRO. In October 2024 the ALTO-100 Phase 2b trial (301 adults, 34 U.S. sites) missed its primary endpoint — no significant improvement over placebo even in the memory-biomarker group. In February 2025, after a blinded eligibility review that narrowed the interim population to 87 biomarker-positive patients, the ALTO-300 Phase 2b interim analysis (NCT05922878) came out favorable, and the study continued toward a ~200-patient final sample with topline expected in mid-2026.

Still running: ALTO-300's Phase 2b continues after a favorable interim analysis, with topline expected mid-2026, while ALTO-100 remains in a separate Phase 2b bipolar-depression study. As of February 2025 Alto reported roughly $168M cash, expected to fund operations into 2028.

Psychiatry's standard practice is trial-and-error prescribing; if biomarkers genuinely predict response, they change both drug development and clinical care.

Alto designed its Phase 2b trials around the biomarker hypothesis — enrolling only patients with a defined EEG or cognitive signature — so each readout tests the platform, not just one molecule.

Alto priced its IPO before any Phase 2b readout, so ALTO-100's miss hit the platform thesis directly and the ALTO-300 interim became the next test of that approach.

Alto's favorable interim rested on a blinded eligibility review that narrowed the population to 87 biomarker-positive patients — data quality ahead of raw enrollment numbers.

The bet was the method, not a single drug: ALTO-100's miss tested the biomarker thesis, and ALTO-300's favorable interim kept it alive — investors underwrite the platform, trials update the odds.

As of February 12, 2025, Alto reported a favorable interim analysis for the ALTO-300 Phase 2b trial and expected topline results in mid-2026, with the final analysis sample expanded to about 200 biomarker-positive patients. ALTO-100 continues in a Phase 2b bipolar-depression study. The company, listed on the NYSE as ANRO since February 2024, said its roughly $168M year-end 2024 cash should fund operations into 2028. The Precision Psychiatry Platform remains the core asset, with additional candidates (ALTO-101, ALTO-203, ALTO-202) in earlier-stage development.