Alto Neuroscience Announces Positive Phase 1 Results for ALTO-101, a Novel PDE4 Inhibitor in Development for Schizophrenia - Seite 2

Phase 1 Study Design and Results

The study was designed to evaluate the safety, tolerability, pharmacokinetics, and adhesion properties of a proprietary transdermal formulation of ALTO-101 compared to oral administration of ALTO-101 in healthy human volunteers. It included a 2-way crossover design consisting of two dosing periods. Fifteen adults between 40-64 years old were enrolled in the study. In period 1, participants received a single oral dose of 1 mg ALTO-101, following a 7-day washout period; in period 2, participants received continual transdermal dosing of 18 mg ALTO-101 for two days – patches were administered once-daily and worn for 24 hours. In both periods pharmacokinetics and tolerability were evaluated during and following treatment to measure absorption and elimination.

Topline Results from the ALTO-101 Phase 1 study include:

• 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 (C_max.) on day 2 of the transdermal dosing was similar to the C_max 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.
  • Dizziness - 40% oral vs. 7.1% TDS
  • Nausea - 20% oral vs. 0% TDS

• All adverse events reported in the study were mild in severity, and there were no reported serious adverse events. No participants discontinued the study due to adverse events.

• The transdermal formulation demonstrated favorable adhesion properties and there were no application site reactions that led to patch removal or intolerance.

Overall, the results from this Phase 1 study indicate a favorable profile for ALTO-101 with higher levels of drug exposure, expected to be within the necessary therapeutic range, and lower rates of adverse events. The pharmacodynamic effects observed with orally administered ALTO-101, which were previously reported by the Company, inform the relevant therapeutic range believed to be required to achieve the desired pro-cognitive and clinical effects.