MicuRx Pharmaceuticals, Inc.,a privately-held biopharmaceutical company, announced that the global partnership Combating Antibiotic Resistant Bacteria Accelerator (CARB-X) has committed up to $5.2 million of non-dilutive financing for IND enablement and subsequent phase 1 clinical studies of MRX-8, also known as PMX-8. This agent is a novel polymyxin antibiotic designed to treat multi-drug resistant Gram-negative infections such as E. coli, P. aeruginosa, K. pneumoniae and A. baumannii.
The antibacterial class of polymyxins includes the drugs colistin and polymyxin B, essential antibiotics with potent activity against Gram-negative pathogens. While very effective, polymyxins are relegated to a last-resort option due to the high incidence of kidney toxicity (nephrotoxicity), with rates up to 60% for the current polymyxin therapy. In addition to nephrotoxicity, polymyxins can manifest neurotoxicity. Due to the lack of agents effective against multi-drug resistant infections, physicians are increasingly using polymyxins, despite the toxicity. Importantly, no novel systemic polymyxin has been approved in over 60 years.
The new agent MRX-8 is designed to overcome the limiting nephrotoxicity of current polymyxins. Current preclinical data demonstrated its high efficacy, with the reduced nephrotoxicity as well as attenuated acute or neuromuscular toxicity, when compared to existing polymyxin drugs.
“We are pleased to have received this support for our MRX-8 program from CARB-X, a non-profit partnership comprised of the key global leaders in the science, development, and the medical use of anti-infectives,” stated Zhengyu Yuan, Ph.D., president and CEO of MicuRx.
CARB-X was created in response to the US government’s 2015 National Action Plan for Combating Antibiotic Resistant Bacteria (CARB) and the UK government’s call in 2016 for a concerted global effort to tackle antibiotic resistance. CARB-X was launched by the US Department of Health and Human Services (HHS)’s Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID/NIH). Funders are BARDA and Wellcome Trust.
“The MicuRx team is excited to rapidly advance MRX-8 from the original concept and into IND development, with the opportunity to augment the armamentarium of effective antibiotics urgently needed to treat serious Gram-negative infections,” stated Mike Gordeev, Ph.D., CSO of MicuRx.
Gram-negative infections represent a growing global health threat inadequately addressed with current antibiotics. Gram-negative pathogens such as E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter bacterial species are the leading cause of serious hospital-acquired infections. These infections represent unmet medical need requiring global R&D efforts to create novel more effective pharmaceuticals. Gram-negative pathogens cause a wide variety of infections, including urinary tract, lung, muscle, bone, and blood diseases. Development of drugs against Gram-negative pathogens is particularly challenging due to a unique cell-wall structure incorporating a protective outer membrane, absent in Gram-positive bacteria, along with diverse mechanisms of acquiring the bacterial resistance to antibiotics.
These critical attributes of Gram-negative pathogens render majority of the current agents ineffective. For example, no single antibiotic is effective in therapy of serious infections due to multiple drug-resistant (MDR) P. aeruginosa, K. pneumoniae, E. coli, or A. baumannii. Therapeutic failure rates for such infections often exceed 40 per cent, particularly in elderly and infant patients.
CARB-X is the world’s largest public-private partnership devoted to early stage antibacterial R&D. Funded by ASPR/BARDA and Wellcome Trust, with in-kind support from NIAID, CARB-X is investing up to $455 million from 2016-2021 to support innovative products from ‘hit-to-lead’ phase through Phase 1 clinical trials. CARB-X focuses on high priority drug-resistant bacteria, especially Gram-negatives.
MicuRx is a privately-held biopharmaceutical company whose mission is to discover and develop effective antibiotics with improved safety to enhance the treatment of serious bacterial infections.