Company: CMND
Filing Date: 2025-01-22
Form Type: 20-F
Source: 0001213900-25-005490
Chunk: 127

Company: Clearmind Medicine Inc.
Filing Date: 2025-01-22
Form: 20-F
Item: Item 4
Chunk 127
---
, although an increase in
activity profile and changes in respirometric parameters, as well as a dose dependent increase in food and water intake were observed.
At the 100 mg/kg dose group, death was observed in 2 out of 8 animals at 1-3 hours after drug administration. Furthermore, a significant
inhibition of wheel running was observed at this dose, indicative of increased anxiety and animals’ stress conditions. Based on
these results the dose of 40 mg/kg was selected as dose for the next phase.

In the second phase mice (total of 20 animals)
were fed high fat diet (HFD) to generate diet-induced obesity for a period of 18 weeks. As control, mice (10 animals) were kept at a standard
diet (STD) for the same period. The induced obese mice were then daily treated with either MEAI (40 mg/kg) by gavage injection for a period
of 28 days or vehicle (saline)(10 animals/group). Due to a technical error in the administration of MEAI, 5 mice died within 24 h of receiving
the compound on Day 1 due to the administration of much higher doses than intended. To supplement for the animal loss, 4 mice on a HFD
from a parallel batch were added, and the experiment was reinitiated with the following group distribution: STD = 10 animals, HFD-Veh
= 8 animals, and HFD-MEAI = 11 animals. At the intended 40 mg/kg/day dose, no animal deaths occurred throughout the 28 days of testing.
During the treatment period mice were monitored for body weight. At the end of the treatment period mice were assessed for food and water
consumption and body composition changes, respiratory assessments, locomotor activity and wheel running patterns, glucose tolerance (ipGTT
test) and insulin sensitivity (ipITT), blood lipid profile and urine chemistry. Animals were euthanized and the kidneys, brain, liver,
and fat pads, were removed and weighed, and samples were either snap-frozen or fixed in buffered 4% formalin. Trunk blood was collected
for determining the biochemical parameters. Food and water consumptions remained the same in all animals. MEAI significantly reduced the
overweight of the obese mice, as well as reduced adiposity associated with obesity. Moreover, MEAI led to normalization of obese induced
hyperglycemia, glucose intolerance and hyperinsulinemia as well as insulin sensitivity, indicating