Brilacidin

Brilacidin (formerly PMX-30063), an investigational new drug (IND), is a polymer-based antibiotic currently in human clinical trials, and represents a new class of antibiotics called host defense protein mimetics, or HDP-mimetics, which are non-peptide synthetic small molecules modeled after host defense peptides (HDPs). HDPs, also called antimicrobial peptides, some of which are defensins, are part of the innate immune response and are common to most higher forms of life. As brilacidin is modeled after a defensin, it is also called a defensin mimetic. Brilacidin (formerly PMX-30063), an investigational new drug (IND), is a polymer-based antibiotic currently in human clinical trials, and represents a new class of antibiotics called host defense protein mimetics, or HDP-mimetics, which are non-peptide synthetic small molecules modeled after host defense peptides (HDPs). HDPs, also called antimicrobial peptides, some of which are defensins, are part of the innate immune response and are common to most higher forms of life. As brilacidin is modeled after a defensin, it is also called a defensin mimetic. Brilacidin is an antibiotic that works by disrupting bacterial cell membranes, mimicking defensins that play a role in innate immunity. Several mimics of antimicrobial peptides, both peptides and non-peptides, have been studied, but none have overcome difficulties to reach the market. Brilacidin, a non-peptide chemical mimic, is an arylamide foldamer designed to replicate the amphiphilic properties of antimicrobial peptides while solving the problems encountered by peptide-based antimicrobials.Brilacidin, a broad-spectrum antibiotic, has potent Gram positive activity and Gram negative coverage, and is highly effective in treating the 'superbug' methicillin-resistant Staphylococcus aureus (MRSA). Brilacidin has low cytotoxicity against mammalian cells while selectively targeting bacteria, directly and rapidly disrupting their membranes, resulting in the bacteria's death. Due to this unique mechanism of action (mimicking the host's natural immune response, proven to be successful in fighting off infections over millions of years of evolution), bacterial antibiotic resistance is less likely to develop. There has not been a new drug approval from a new class of antibiotics since 1987. While six antibiotics have been approved over the last year, they are all adaptations of existing antibiotic classes. None of the recently approved novel antibiotics represent entirely new classes. Novel antibiotics are crucial as antibiotic resistance poses a global health risk. The World Health Organization, warning of a 'post-antibiotic era' has stated that antimicrobial resistance (AMR) is a 'problem so serious that it threatens the achievements of modern medicine'. Leveraging advanced computational bioinformatics, brilacidin and other defensin mimetics were first developed by University of Pennsylvania-based researchers. Their efforts were consolidated, and officially incorporated, in 2002, under the company name PolyMedix. PolyMedix conducted pre-clinical and clinical research with brilacidin through a completed Phase 2a human clinical trial with positive results. After discontinuing a clinical trial for an unrelated compound PolyMedix filed for Chapter 7 bankruptcy protection on April 1, 2013. Cellceutix acquired the PolyMedix assets and intellectual property, including the licenses and patents for brilacidin and the rest of the HDP-mimetic pipeline, from bankruptcy court which on September 4, 2013 approved Cellceutix's stalking horse bid. Cellceutix is pursuing other clinical applications of brilacidin and related anti-infective HDP-mimetic compounds, including their prophylactic use on implanted medical devices, having already entered into a material transfer agreement with a division of a large U.S. pharmaceutical company. An active clinical trial, brilacidin for oral mucositis is detailed below. In pre-clinical research, a mouthwash formulation of brilacidin was well-tolerated and efficacious for oral mucositis, significantly reducing the number of days with ulcerations and significantly reducing the mucositis scores in a dose dependent manner. Pre-clinical research has shown potential for brilacidin for ocular, Otic, and diabetic foot ulcers. PolyMedix advanced brilacidin through early stage human clinical trials to a completed Phase 2a proof-of-concept clinical trial. Since acquisition, brilacidin has to date completed a Phase 2b clinical trial with positive results. Results, as detailed below, showed brilacidin compared favorably with Daptomycin, though administered in a single-dose as compared to Daptomycin's 7-day dosing regimen. Discussions presently are underway between Cellceutix and the FDA to begin a pivotal Phase 3 trial for ABSSSI. Plans and trial design for the Phase 3 clinical trail(s) are expected be made public after the post-P2b clinical trial with the FDA expected in June 2015 Brilacidin was granted the Qualified Infectious Disease Product (QIDP) designation by the FDA under the Generating Antibiotic Incentives Now Act of 2011 (GAIN Act). Receiving QIDP designation means that brilacidin is now eligible for additional FDA incentives in the approval and marketing pathway, including fast track designation and priority review for development and a five-year extension of market exclusivity.