Company: APM
Filing Date: 2025-10-06
Form Type: S-4
Source: 0001213900-25-096656
Chunk: 244

Company: Aptorum Group Ltd
Filing Date: 2025-10-06
Form: S-4
Chunk 244
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 which appears to target the products produced by bacterial genes that facilitate the successful colonization and survival of the bacterium in the body or that cause damage to the body’s systems. These products of bacterial genes are referred to as “virulence expression.” Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to overcome the emergence and increasing prevalence of antibiotic -resistantbacteria. Professor Richard Kao from The University of Hong Kong (who is also the Founder and Principal Investigator of Acticule and Inventor of ALS -1, ALS -2, ALS -3and ALS -4) initiated a high throughput approach for screening compounds which are active against virulence expression, which resulted in the discovery of ALS -1, ALS -2, ALS -3and ALS -4. ALS -4targets 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 -4may 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 -4demonstrates potent activity against Staphylococcus aureus pigment formation in vitro, as indicated in Figure1, 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. 123 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 Efficacy of ALS-4 in a MRSA Wound Infection Mouse Model A study conducted by a third -partycontract research organization, assessed ALS -4’s effect in the healing of open wounds infected with MRSA in a