Recently listed Alto Neuroscience Inc (NYSE:ANRO) released results from its healthy volunteer Phase 1 study of ALTO-101, a novel PDE4 inhibitor in development for cognitive impairment associated with schizophrenia (CIAS).

Results from the study demonstrated favorable tolerability and improved pharmacokinetics of ALTO-101 when administered via a transdermal delivery system (TDS or a patch) compared to oral administration.

The drug exposure levels achieved with the transdermal formulation were significantly greater than systemic exposure with oral administration while also reducing typical class-wide adverse events.

The company plans to initiate a proof-of-concept study evaluating ALTO-101 in patients with CIAS in the first half of 2024, with topline data expected in the second half of 2025.

ALTO-101 delivered transdermally resulted in significantly higher and consistent drug concentrations compared to oral administration:

• Area under the curve (AUC) was 62% and 170% higher on day 1 and day 2, respectively, for the transdermal formulation relative to oral administration (day 1 p=0.01; day 2 p<0.001).
• The maximum concentration (Cmax.) on day 2 of the transdermal dosing was similar to the Cmax of 1mg of orally administered ALTO-101 (27.9 ng/mL for TDS vs. 30.1 ng/mL oral).
• Plasma concentrations for the transdermal formulation remained stable throughout the 24 hours of dosing on day 2.
• ALTO-101 delivered transdermally resulted in substantially lower class-related adverse events typically associated with PDE4 inhibitors.
• All adverse events reported in the study were mild, with no reported serious adverse events.
• The transdermal formulation demonstrated favorable adhesion properties, and no application site reactions led to patch removal or intolerance.

Upon achieving the pharmacokinetic profile for ALTO-101, MEDRx is eligible to receive a milestone payment of $1.5 million from Alto in cash and stock.

William Blair views the update as an incremental positive as the company addresses otherwise likely development-limiting tolerability issues from one of its earlier stage programs. The analyst reiterates the Outperform rating on Alto.

Alto is in the early stages but is uniquely positioned in the neuropsychiatry drug development landscape with a positively biased risk/reward profile at current trading levels.

Data from this trial could de-risk Alto's Precision Psychiatry Platform approach with the next readout leveraging EEG-based biomarkers identified by Alto Scope in the Phase IIb trial of ALTO-300 in adjunctive MDD therapy.

Price Action: ANRO shares are up 2.13% at $13.93 at the last check Tuesday.

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