News Release Dated April 24, 2024

MedRx Co., Ltd.

Yonehiro Matsumura, CEO

Stock code: 4586, TSE Growth

MEDRx Collaboration Partner, Alto Neuroscience, Announces Positive Phase 1 Results for ALTO-101,

a Novel PDE4 Inhibitor in Development for Schizophrenia

  • ALTO-101demonstrated a favorable pharmacokinetic and tolerability profile; novel transdermal formulation delivered significantly greater drug exposure and fewer adverse events typically associated with

PDE4 inhibitors -

    • First-in-humanachievement of target exposure with proprietary transdermal patch formulation developed in partnership between Alto Neuroscience and MEDRx -
  • Proof-of-conceptstudy in cognitive impairment associated with schizophrenia (CIAS) to be initiated by Alto

  • Neuroscience in 1H 2024 -

The pharmacokinetic curve illustrates stable drug exposure and achievement of the desired plasma concentration with the transdermal formulation as compared to orally administered ALTO-101.

MEDRx Company Limited (MEDRx) today announced that Alto Neuroscience, Inc. (NYSE: ANRO), its development partner for a proprietary transdermal formulation of Alto's novel PDE4 inhibitor, reported positive results from its healthy volunteer Phase 1 study of ALTO-101. Results from the study demonstrated favorable tolerability and improved pharmacokinetics of ALTO-101 when administered via a transdermal delivery system (TDS) compared to oral administration. The drug exposure levels achieved with the transdermal formulation were significantly greater than systemic exposure with oral administration while

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The transdermal formulation demonstrated favorable adhesion properties and there were no application site reactions that led to patch removal or intolerance.
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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.
ALTO-101delivered transdermally resulted in substantially lower class-relatedadverse events typically associated with PDE4 inhibitors.
o Dizziness - 40% oral vs. 7.1% TDS o Nausea - 20% oral vs. 0% TDS
also reducing typical class-wideadverse events. Alto plans to initiate a proof-of-conceptstudy evaluating ALTO-101in patients with CIAS in the first half of 2024, with topline data expected in the second half of 2025.
"We are pleased to demonstrate transdermal administration of ALTO-101results in significantly greater, stable drug concentration with a once-dailyformulation that is well-tolerated."said Yonehiro Matsumura, Ph.D., CEO MEDRx. "Towards "For the Patients" of MEDRx's philosophy, these positive results are important first steps that MEDRx's transdermal technology potentially helps patients with CIAS and central nervous system disorder to address significant unmet needs and benefit through Alto-101."
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-101compared to oral administration of ALTO-101in healthy human volunteers. It included a 2-waycrossover design consisting of two dosing periods. Fifteen adults between 40-64years old were enrolled in the study. In period 1, participants received a single oral dose of 1 mg ALTO-101,following a 7-daywashout period; in period 2, participants received continual transdermal dosing of 18 mg ALTO-101for two days - patches were administered once-dailyand 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-101Phase 1 study include:
ALTO-101delivered transdermally resulted in significantly higher, and consistent, drug concentrations compared to oral administration:
o 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). o 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).
o Plasma concentrations for the transdermal formulation remained stable throughout the 24 hours of dosing on day 2.

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

Under the terms of the development agreement between Alto and MEDRx, upon this achievement of the desired pharmacokinetic profile for ALTO-101, MEDRx is eligible to receive a milestone payment of $1.5 million from Alto that is payable in a combination of cash and common stock of Alto Neuroscience.

About MEDRx Company Limited

MEDRx is a pharmaceutical formulation development company that aims to improve people's health and quality of life by developing new dosage forms of medicines and leveraging novel transdermal absorption technology. For more information, visit https://www.medrx.co.jp/

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Contact: MEDRx Co., Ltd. Management Department E-mail: info@medrx.co.jp

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Medrx Co. Ltd. published this content on 24 April 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 23 April 2024 23:53:07 UTC.