Company: APM
Filing Date: 2025-11-17
Form Type: F-1
Source: 0001213900-25-111548
Chunk: 204

Company: Aptorum Group Ltd
Filing Date: 2025-11-17
Form: F-1
Chunk 204
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aphylococcus 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 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. 116 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-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% for topical Mupirocin 2%. The results are further illustrated in the graph below. (Figure 2) During the study period, body weight monitoring was conducted as a safety parameter. No significant adverse effects or safety concerns were observed in the ALS-4 treatment group. This study was designed as a proof-of-concept efficacy evaluation, with comprehensive toxicology assessments subsequently completed during the IND-enabling studies phase. 117 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 Efficacy of ALS-4 in a Bacteraemia Mouse Model In a further round of in vivostudies, 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