Company: CMND
Filing Date: 2025-01-22
Form Type: 20-F
Source: 0001213900-25-005490
Chunk: 125

Company: Clearmind Medicine Inc.
Filing Date: 2025-01-22
Form: 20-F
Item: Item 4
Chunk 125
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AI at doses of 40 mg/kg/day (p<0.001) and above produced
a marked and statistically significant reduction in alcohol consumption as compared to controls, although the reduction in alcohol consumption
did not directly correlate with an increase of MEAI dosage. P-value is a statistical measure of significance used to predict the probability
of outcomes being replicable. In the case of this study, a p-value of “p<0.001” means that the aforementioned study, when
replicated using MEAI at doses of 40 mg/kg/day, have less than a one in one thousand chance of being incorrect. There was no effect at
20 mg/kg/day.

There were no clinical abnormalities observed in
most of the mice during this study. One rat from the 20mg/kg/day group showed Dyspnea, Decrease Motor Activity during day 38 of the study.
Another rat from the 60 mg/kg group showed necrotic tail during day 45 of the study. In addition, mortality was observed in two animals
from the high dose groups. However, it is important to take into consideration that these animals were treated with MEAI following a prolonged
period of alcohol consumption. Supporting evidence to the harmful effect of alcohol consumption can be found in the gross pathology analysis
which exhibited macroscopic findings mostly in the liver, kidneys, heart and spleen, of all groups including the control.

Based on the results from the pre-clinical studies
described above, we have conducted and continue to conduct our own pre-clinical studies in the United States and China.

In order to unravel additional modes of action
by which MEAI may exert its therapeutic activity it was tested both in in-vitro and in-vivo contexts by characterizing its interaction
with receptors, and by assessing its efficacy to mitigate additional disorders, respectively. These studies were conducted under the sponsors
responsibility and are not part of the IND-enabling studies that will be discussed later.

Eurofins Binding Studies

A few in-vitro studies were conducted to unravel
the molecular targets MEAI interacts with. For this, MEAI binding was evaluated using a panel of CNS receptors and enzymes (87 Safety
Screen Panel and 168 GPCR Max Screen Panel). Results showed that MEAI’s main inhibition effect was obtained on 5-HT agonist radioligand,
reaching a 76.8% inhibition of 5-HT2b receptor (compared to 100% inhibition with DOI), 62.6