Sexual HealthPolyMedix Receives Regulatory Clearance To Initiate Second Phase I Clinical Study Of Novel Systemic Antibiotic Compound
PolyMedix, Inc., an emerging biotechnology company developing acute care products for infectious diseases and acute cardiovascular disorders, has received a notice of no objection from Health Canada for the Company"s Clinical Trial Application ("CTA") for its defensin mimetic antibiotic compound, PMX-30063. This notice of no objection allows for the initiation of the second human clinical study in Canada. PMX-30063 is a defensin mimetic antibiotic compound, the first of an entirely new class of antibiotic drugs that is believed to work in such a way that makes bacterial resistance unlikely to develop.
This second Phase I clinical trial will assess the safety of PMX-30063 given repeatedly over a period of several days. Healthy volunteers will each receive a dose of PMX-30063 every 12, 24, or 48 hours for a total of 5 to 10 doses. The previous study provided information on the time course of the drug in humans after single doses, indicating that regular once-daily dosing would provide sufficient drug levels for treating the infections to be targeted. This study is planned to confirm those expectations, and comparison with doses given every 12 or 48 hours will provide valuable data on how the drug might be used most effectively against target bacteria.
Provided that we successfully complete this second clinical study, and provided that additional financing has been obtained, PolyMedix plans to request regulatory permission to test the drug on actual infections in hospitalized patients, in Phase II clinical studies.
On December 10, 2008 PolyMedix announced the results of the first Phase I human clinical study with PMX-30063. That ascending single-dose intravenous pharmacokinetic and safety study met the necessary Phase I goals of defining both a limiting single dose and the plasma distribution/elimination kinetics. A comparison between microbiologically effective drug levels (from preclinical studies in animals) and the plasma drug levels measured in that first human study suggests that it should be possible to achieve clinically therapeutic levels with daily doses of PMX-30063 which are lower than those associated with any adverse effects seen in the single dose study. This Phase IB trial is the planned next step in the continued clinical development of PMX-30063.
About PMX-30063
Distinguishing it from other antibiotic compounds currently on the market, PMX-30063 is a synthetic chemical mimic of host defense proteins, one of the oldest and most effective antimicrobial defense systems found in virtually all living creatures. PolyMedix believes that PMX-30063 is the first small molecule mimetic of host defense proteins intended to treat systemic infections to enter clinical trials.
PMX-30063 and other PolyMedix antibiotic compounds have distinct properties which set them apart from traditional antimicrobial molecules and materials, including:
- A novel mechanism of action that makes development of bacterial resistance unlikely - the direct biophysical disruption of bacterial cell membranes;
- Activity against both Gram-positive and Gram-negative bacteria, and in particular, activity against 146 different strains of Staphylococcus bacteria, including 89 drug-resistant strains of Staph bacteria;
- PMX-30063 is bactericidal, meaning it kills bacteria directly, rather than simply stopping reproduction (bacteriostatic) as do many current antibiotics;
- PMX-30063 is rapidly bactericidal, and faster acting than many antibiotics; and
- PMX-30063 is active against drug-resistant bacteria, including clinical isolates of multiple vancomycin- and methicillin-resistant strains.
Primitive life forms, such as molds, secrete compounds like penicillin to protect themselves from bacteria. This forms the basis for conventional antibiotics - compounds which act against biochemical targets or pathways in bacterial cells. Multi-cellular organisms, such as insects, animals, and mammals, possess a more complex, first-line immune system defense against bacterial infections - the host defense proteins. Host defense proteins are part of the non-humoral (that is, not involving antibodies) response that keep humans from rapidly succumbing to infections. Biologists have discovered many different classes of natural host-defense peptides. Although these molecules possess a diverse array of structures, their physicochemical properties are similar. All are amphiphilic, meaning they have a combination of positively electrically charged properties, and hydrophobic (water-hating, fat-loving) chemical properties. This amphiphilic structure is believed to be responsible for host defense peptides" antimicrobial activity and their ability to directly disrupt bacterial cell membranes. Among the most common and well-studied antimicrobial peptides are the defensins found in humans, the magainins found in frogs, and the cecropins and melitins found in insects.
PMX-30063 was designed to mimic the amphiphilic structure of the host defense proteins, but with a completely synthetic, non-peptide, small molecule structure. PMX-30063 directly disrupts bacterial cell membranes; a mechanism shared with the host defense proteins but which we believe is unique among known antibiotic drugs. Because of this mechanism, it is believed that bacterial resistance is less likely to develop with PMX-30063 than has been experienced with many conventional antibiotic drugs. Multiple serial passage experiments conducted by PolyMedix and others on PMX-30063 and related PolyMedix antibiotic compounds support our view of a lower likelihood of developing resistance.
PolyMedix, Inc.