Company: CMND
Filing Date: 2025-01-22
Form Type: 20-F
Source: 0001213900-25-005490
Chunk: 121

Company: Clearmind Medicine Inc.
Filing Date: 2025-01-22
Form: 20-F
Item: Item 4
Chunk 121
---
, an NMDA receptor antagonist,
approved by the FDA in March 2019 and marketed by Janssen Pharmaceutical Companies of Johnson & Johnson, and (ii) a fixed dose combination
of olanzapine and fluoxetine hydrochloride, which are individually available generically. These treatments are typically used alongside
antidepressants and other treatments used in earlier lines of therapy for depression. Psychosocial interventions and non-pharmacological,
somatic treatments may also be used for patients.

Pre-Clinical Studies

So far, only pre-clinical studies have been conducted
with MEAI, including In-vitro and In-vivo studies. Some of these studies were conducted by outside research organizations in the United
States France, Israel and China

Volcani Center and Hebrew University Study

In one of these studies, conducted by researchers
at the Ministry of Agriculture and Rural Development, Volcani Center and Hebrew University, MEAI’s pharmacokinetic (PK) profile
was determined in a rat model. The study included 84 male rats that were administered 0-90 mg/kg body weight dosages, and blood samples
were collected at 5 minutes, 10 minutes, 20 minutes, 40 minutes, 60 minutes, 1 hour, 2 hour, 4 hour, 7 hour and 24 hour intervals. MEAI
displayed extensive total clearance and a very short plasma and brain half-life. The significance of this study is that a high portion
of MEAI reached its target organ - the brain, in a rapid manner. This is important as it demonstrated a substantial dosage of MEAI
will reach the brain without “going to waste” during the distribution in the body. In addition, this study demonstrated that
a dose of 10 mg/kg in the rat was considered to be the NOAEL (No-observed-adverse-effect level) which corresponds to 1.6 mg/kg body weight
in humans. Therefore, it was determined that a single oral dosage of 1 mg/kg/day of MEAI in humans, is not expected to result in clinically
acute severe adverse effects. The only mortality observed in the study occurred in the 90 mg/kg dosage group, where one rat was found
dead after dosing. Gross pathology showed that the animal had urine hemolysis, swollen kidneys and bleeding in the spleen. As it was the
only mortality observed it was considered incidental and not related to MEAI.

Kimron Veterinary Institute Study