MicuRx Presents Innovative Antibiotic Research Results at the 7th World Bronchiectasis Conference

Shanghai MicuRx Pharmaceutical Co., Ltd. (“MicuRx”，688373.SH) presented the latest research progress on their novel antibiotic pipeline products, MRX-5 and MRX-8, at the 7th World Bronchiectasis Conference (WBC) held in Dundee, Scotland, from July 4 to 6, 2024. These research results provide new hope for the future treatment of Nontuberculous Mycobacteria (NTM) lung disease and Pseudomonas aeruginosa infections.

Conference Background
The World Bronchiectasis Conference is a leading global academic conference focused on the research and treatment of bronchiectasis. This conference brings together top scientists and clinical experts from around the world to discuss the latest research developments, clinical management strategies, and the development of new therapies for bronchiectasis.

Research Highlights
As a biopharmaceutical company dedicated to developing innovative anti-infective drugs, MicuRx presented three significant research results in poster presentation at the conference. These studies further support the potential of MRX-5 and MRX-8 in the treatment of specific infections：
 In Vitro and In Vivo Activity of A Novel Leucyl-tRNA Synthetase Inhibitor Against Mycobacterium Abscessus
The active drug MRX-6038 was very potent against M. abscessus clinical isolates in vitro with MIC90 0.5 mg/L while the control drug clarithromycin MIC90 was 4 mg/L. MRX-6038 greatly reduced the resistance frequency of standard of care drugs (Ethambutol, Clarithromycin, Rifabutin, Clofazimine, Amikacin, Imipenem, Ciprofloxacin) by more than 10 to 100,000 folds, demonstrating the potential for combination with the background therapy. Oral prodrug MRX-5 was tested in mice with lung infections due to M. abscessus isolates, and efficacy was demonstrated against infections with both clarithromycin-sensitive and clarithromycin non-susceptible isolates.

 In Vitro Activity of Novel Leucyl-tRNA Synthetase Inhibitor Against Mycobacterium Avium Complex
MRX-6038, the major activedrug of MRX-5, has demonstrated potent in vitro activity against Mycobacterium avium clinical isolates including isolates not susceptible to clarithromycin. When MRX-6038 was combined with Clarithromycin, Rifabutin, Amikacin, and Ethambutol, the resistance frequency of these standard of care drugs was greatly reduced to below 6.5×10-11. Further studies are warranted for the evaluation of MRX-6038 for the treatment of Mycobacterium avium pulmonary disease.

 In Vitro and In Vivo Activity of A Novel Antibiotic In The Polymyxin Class Against Pseudomonas Aeruginosa
MRX-8 demonstrated potent in vitro activity against P. aeruginosa including tobramycin and amikacin resistant clinical isolates. In mouse models with P. aeruginosa lung infections of both tobramycin-sensitive and tobramycin-resistant isolates, nebulized MRX-8 treatment significantly decreased bacterial load in the lung tissues, demonstrating bactericidal activity.

About MRX-8
MRX-8 is a novel polymyxin antibiotic developed by MicuRx, primarily used to treat severe infections caused by multidrug-resistant Gram-negative bacteria. Traditional polymyxins are limited in clinical use due to nephrotoxicity and neurotoxicity. Through meticulous structural design, MRX-8 not only maintains or enhances therapeutic efficacy but also significantly improves safety by reducing these potential toxic risks.

In 2022, MRX-8 completed Phase I clinical trials in the United States. In 2023, it completed Phase I enrollment in China, with primary study results released in June 2024. These trial results indicated that MRX-8 achieved the desired therapeutic levels in the human body at the expected clinical doses for infections caused by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Besides systemic administration, the company plans to explore the development of an inhaled formulation of MRX-8 to uncover its clinical and commercial value in targeted treatment of chronic lung infections.

About MRX-5 and NTM
MRX-5 is a novel benzoxaborole antibiotic developed by MicuRx for infections caused by NTM.
NTM is a common pathogen causing bronchiectasis. In recent years, the incidence of NTM diseases has rapidly increased, becoming a significant public health issue. [1] Among diseases caused by NTM, Mycobacterium avium complex and Mycobacterium abscessus complex account for 70%-95% of NTM diseases. [2] The main clinical symptoms of NTM pulmonary infections include persistent cough, sputum production, chest pain, shortness of breath, fatigue, weight loss, and malaise. [1]
Preclinical data indicates that MRX-5 has good antibacterial activity against most common NTM pathogens and has demonstrated good safety in animal studies. Additionally, its characteristics of minimal drug interactions, low resistance potential, and oral availability make it an ideal candidate for the treatment of chronic infections. Currently, MRX-5 is undergoing Phase I clinical trials, offering a promising new treatment option for patients with NTM diseases.

References：
[1] Chinese Medical Association Tuberculosis Branch. Guidelines for the Diagnosis and Treatment of Nontuberculous Mycobacterial Diseases (2020 Edition). Chinese Journal of Tuberculosis and Respiratory Diseases, 2020, 43(11): 918-946. DOI: 10.3760/cma.j.cn112147-20200508-00570.
[2] Luo Kuo, Chen Shanze, Chen Rongchang, et al. Host Factors of Nontuberculous Mycobacterial Diseases. Chinese Journal of Tuberculosis and Respiratory Diseases, 2022, 45(7): 716-720. DOI: 10.3760/cma.j.cn112147-20211210-00872.