Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 196

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 196
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 the characteristic golden color. This pigment has proven
to be an important factor in promoting bacterial invasion as well as rendering the bacteria resistant to attack from reactive oxygen species
(ROS) and neutrophils. In other words, pigmented bacteria have increased resistance to the host’s immune defenses. ALS-4 may have
particular value if it can be shown to be an effective therapy in situations where a Staphylococcus aureus infection is resistant to available
antibiotics (i.e., where the pathogen is MRSA).

In a study by the inventor,
Prof. Richard Kao, ALS-4 demonstrates potent activity against Staphylococcus aureus pigment formation in vitro, as indicated in Figure
1, with an IC (IC is defined as the concentration of a drug which inhibits half of the maximal response
of a biochemical process. In this case, inhibition of the formation of the golden pigment is the response) equal to 20 nM.

<div align='center'>97</div>

Figure 1

Figure 1: In vitro pigment inhibition by compound
ALS-4: Inhibition of staphyloxathin (the golden pigment in S. Aureus) in the presence of increasing concentrations of ALS-4

A study conducted by a third-party
contract research organization, assessed ALS-4’s effect in the healing of open wounds infected with MRSA in a mouse model. Compared
with topical dosing of 2% Mupirocin and oral dosing of Linezolid at 100mg/kg twice a day, oral dosing of ALS-4 at 30mg/kg twice a day
showed statistically significant improvement in wound healing. Specifically, at the end of the study on Day 7, ALS-4 exhibited 63.8% of
wound closure compared with 48.4% for oral Linezolid and 43.2% for topical Mupirocin 2%. The results are further illustrated in the graph
below.

<div align='center'>98</div>

Figure 2

| * | Unpaired student’s t-test, p<0.05 |

Figure 2: Result of study
on ALS-4’s effect in the healing of open wounds infected with MRSA in a mouse model

In a further round of in vivo studies, conducted by a third-party contract research organization, in a non-lethal MRSA bacteraemia mouse model, the mice
were orally administered with different doses of ALS-