PolyMedix Successfully Completes Phase 1 Exposure Escalation Safety Study With PMX-30063 Antibiotic
In Vitro Study with PMX-30063 Shows Activity Against NDM-1Drug Resistant Bacteria
RADNOR, Pa.--(BUSINESS WIRE)--Feb 24, 2011 - PolyMedix, Inc. (OTC BB: PYMX), an emerging biotechnology company focused on developing new therapeutic drugs to treat infectious diseases and acute cardiovascular disorders, today announced the successful completion of a Phase 1 exposure-escalation clinical study with its synthetic defensin-mimetic antibiotic, PMX-30063. The study results showed that PMX-30063 may be safely administered at a high dose for more than five days. These data support dosing levels being studied in the current Phase 2 efficacy study in Staph infections. The results also showed very similar pharmacokinetic profiles of PMX-30063 in male and female subjects.
This randomized, double-blind, placebo-controlled Phase 1 study enrolled twenty male and female subjects at a single site in the United States. Subjects randomized to PMX-30063 received an initial intravenous loading dose of PMX-30063 followed by a daily maintenance dose for up to 14 days. Pharmacokinetic sampling and other neurosensory tests were conducted during treatment and for 30-days thereafter. The doses of PMX-30063 administered were identical to the highest dose regimen currently being administered for five days in PolyMedix's Phase 2 clinical trial in patients with ABSSSI (Acute Bacterial Skin and Skin Structure Infections) caused by Staphylococcus bacteria, including MRSA.
Similar to results from two previously completed Phase 1 clinical studies with PMX-30063, the most frequently reported side effects included transient sensations of numbness and tingling affecting the lips, face, and fingers (called paraesthesia). These sensations did not worsen over the course of the study and resolved on their own without any treatment shortly after discontinuation of PMX-30063 administration. There were no significant clinical neurosensory abnormalities noted. Only one subject discontinued from the study due to paraesthesia. Several subjects were discontinued by the investigator after receiving between nine and thirteen days of dosing due to increased blood pressure and heart rate, for which there were no associated clinical signs or symptoms. After nine days of dosing, there was one reportable adverse event of atrial fibrillation that was fully reversed within a few hours following dosing. As seen in previous Phase 1 clinical studies, there were a few minor and transient increases in liver enzymes that were not clinically significant. All subjects demonstrated complete return to normal clinical parameters and reported no adverse effects by the time of the last follow up visit. There were no differences in the pharmacokinetics profiles between males and females.
To identify the mechanism of action for the paraesthesias observed in subjects receiving higher doses of PMX-30063, PolyMedix has conducted additional in vivo and in vitro studies. Results from these studies suggest that the paraesthesias may be related to temporary interactions with certain specific sodium, potassium, or acid sensing ion channels which are found on peripheral sensory nerve fibers.
“We are pleased with these Phase 1 results which show the safety of PMX-30063 at a high dose level and beyond five days of treatment,” commented Dr. Bozena Korczak, Senior Vice President, Drug Development and Chief Development Officer of PolyMedix. “Our mechanistic studies now provide us with a better understanding of the processes underlying the sensory effects of PMX-30063, which is similar to that reported for a number of currently marketed drugs. We find this information, coupled with the pharmacokinetic data, to be encouraging and supportive of our clinical activities and plans for the development of PMX-30063. We look forward to the results from our ongoing Phase 2 efficacy trial in Staph infections.”
Separate from the Phase 1 clinical study, PolyMedix has also conducted in vitro assays in which PMX-30063 has shown bactericidal activity against the NDM-1 drug-resistant strain of Klebsiella pneumonia. NDM-1 (New Delhi metallo-beta-lactamase-1) is an enzyme carried by some bacteria that confers resistance to many antibiotics, including carbapenems. PolyMedix has previously published results showing that PMX-30063 is bactericidal against 181 different drug-resistant and multi-drug resistant strains of Staphylococcus bacteria (different MRSA strains). These in vitro assays show that PMX-30063 is also active in killing the NDM-1 drug-resistant strain of Klebsiella pneumonia. The results showed no substantial differences between the effective concentrations for the NDM-1 and non-NDM-1 strains, indicating that the resistance mechanism associated with NDM-1 may not be effective against PMX-30063.
PolyMedix intends to conduct additional analysis on these data prior to submission for publication or presentation at future scientific meeting(s).
PolyMedix's novel antibiotic compound, PMX-30063, is a small-molecule designed to mimic the activity of human host-defense proteins (HDPs), the body's natural defense against bacterial infections. HDPs kill bacteria by directly targeting bacterial membranes and disrupting them. Widespread resistance to this unique mechanism of action has not developed despite millions of years of evolution. With PMX-30063 designed to mimic HDPs, we believe that resistance is also unlikely to evolve to this novel antibiotic, making PMX-30063 a potential addition to the alternatives to combat the growing problem of bacterial resistance to currently available antibiotics. There are many forms of Staph bacteria which are antibiotic resistant. Preclinical studies with PMX-30063 have demonstrated bactericidal activity against 181 different drug-resistant forms of Staph bacteria, including those strains resistant to marketed drugs. We believe the activity of PMX-30063 against a broad range of Staph bacteria, including those non-responsive to currently marketed drugs such as vancomycin, daptomycin, and linezolid, distinguishes it among available and investigational antibiotic drugs.
About PolyMedix, Inc.
PolyMedix is a publicly traded biotechnology company focused on the development of novel drugs for the treatment of serious infectious diseases and acute cardiovascular disorders. PolyMedix uses a rational drug design approach to create non-peptide, small-molecule drug candidates. PolyMedix's lead antibiotic compound, PMX-30063, is currently in a Phase 2 clinical trial for treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) caused by Staph. PMX-30063 is a small-molecule that mimics the mechanism of action of human host defense proteins, a mechanism that is distinct from currently approved antibiotic drugs and is intended to make bacterial resistance unlikely to develop. PolyMedix's lead heptagonist compound, PMX-60056, is in a Phase 2 clinical trial in patients undergoing PCI procedures. PMX-60056 is designed to reverse the anticoagulant activity of both heparin and low molecular weight heparins (LMWH). PolyMedix believes that PMX-60056 could potentially be a safer and easier to use anticoagulant reversing agent, with broader activity, than the currently approved therapy for reversing heparin and LMWH. In addition to its small molecule therapeutics, PolyMedix has polymeric formulations with the same mechanism of action as PMX-30063, PolyCides®. PolyCides are intended for use in antimicrobial biomaterials applications as additives to paints, plastics, and textiles to create self-sterilizing products and surfaces.
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 that involve risks, uncertainties and assumptions that could cause PolyMedix's actual results and experience to differ materially from anticipated results and expectations expressed in these forward looking statements. PolyMedix has in some cases identified forward-looking statements by using words such as “anticipates,” “believes,” “hopes,” “estimates,” “looks,” “expects,” “plans,” “intends,” “goal,” “potential,” “may,” “suggest,” and similar expressions. Among other factors that could cause actual results to differ materially from those expressed in forward-looking statements are PolyMedix's need for, and the availability of, substantial capital in the future to fund its operations and research and development, and the fact that PolyMedix's compounds may not successfully complete pre-clinical or clinical testing, or be granted regulatory approval to be sold and marketed in the United States or elsewhere. A more complete description of these risk factors is included in PolyMedix's filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. PolyMedix undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events, except as required by applicable law or regulation.
Posted: February 2011