Aptorum Group Limited (NASDAQ:APM, Euronext Paris: APM))))) ("Aptorum Group"), a biopharmaceutical company focused on novel therapeutics including the development of next-generation approach therapeutics targeting antimicrobial resistance, announced two sets of positive data showing both significant in vivo activities of its lead compound ALS-4 against Methicillin-Resistant Staphylococcus aureus (MRSA, one of the "super-bugs") in wound infected and bacteraemia mouse models, respectively when compared to prevailing antibiotics.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200831005403/en/
*Unpaired student's t-test, p<0.05 (Photo: Business Wire)
ALS-4 is currently undergoing final stages of IND enabling studies, which involves a 14-Day oral toxicity in rats and dogs, a functional observation battery study in rats and a cardiovascular telemetry and respiratory study in dogs. Subject to the final IND-enabling studies results, ALS-4 is on track to target the regulatory submission in Q4 2020 subject to which to commence Phase I clinical trials in Canada
"Despite the two current mainstay treatments, vancomycin and daptomycin, being the only FDA approved antibiotics for MRSA bacteraemia thus far, patient mortality, morbidity and recurrence rates remain significant1. With the fragile antibiotic pipeline being at risk globally, antimicrobial resistance issues continue to gain significant attention from global bodies including the World Health Organization and the FDA, as well as the pharmaceutical industry. We believe that our oral ALS-4 drug based on a novel first-in-class anti-virulence concept can potentially tackle a variety of infections related to MRSA, including (but not limited to) bacteraemia and skin & soft tissue infections, subject to the respective clinical trials. We are greatly encouraged by the data because ALS-4 appears to be effective against MRSA superbug and could be a potential alternative and sustainable treatment for different MRSA indications including, but not limited to, MRSA bacteraemia and skin infections. ALS-4's anti-virulent properties are a novel approach in tackling antimicrobial resistance issues as encouraged by recent global action plans. We are also pleased to report that our IND enabling studies are also at their final stages and we remain on track to target regulatory submission to commence phase 1 clinical trials," said Mr. Darren Lui, President and Executive Director of the company.
Efficacy of ALS-4 in a MRSA Wound Infection Mouse Model
A recent 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.
Efficacy of ALS-4 in a Bacteraemia 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-4 from 0.3 to 30mg/kg twice a day for 7 days, compared to those who received vancomycin only group (3mg/kg of vancomycin administered intravenously) and a no treatment control group.
At the conclusion of the study on Day 7, ALS-4 brought a statistically significant reduction in bacterial counts in major organs such as the kidneys, lungs, liver and spleen compared with the no drug control and vancomycin only groups (unpaired student's t-test, p<0.05). This is in addition to the previous in vivo results announced in February 2020, whereby ALS-4 demonstrated on a statistically significant basis better survival rates (56% vs 0% control group) in the lethal MRSA bacteraemia rat model and higher reduction of bacterial load (by 99.5% against the control group) in the non-lethal MRSA bacteraemia rat model.