Company: APM
Filing Date: 2025-10-14
Form Type: 424B5
Source: 0001213900-25-098635
Chunk: 14

Company: Aptorum Group Ltd
Filing Date: 2025-10-14
Form: 424B5
Chunk 14
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 approach for screening compounds which are active against virulence expression, which resulted in the
discovery of ALS-1, ALS-2, ALS-3 and ALS-4.

ALS-4 targets an enzyme essential
for Staphylococcus aureus (including MRSA) survival in vivo. This enzyme is involved in the production of Staphyloxanthin, a carotenoid
pigment produced by Staphylococcus aureus including MRSA, and is responsible for 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).

<div align='center'>S-5</div>

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 IC50 (IC50 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.

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. The study
utilized 5 mice per treatment group to evaluate therapeutic efficacy. 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%