PolyMedix receives clearance to initiate phase I clinical study of novel systemic antibiotic compound

May 9 2008

PolyMedix, Inc. 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 human clinical studies in Canada. PMX-30063 is the first defensin mimetic antibiotic compound cleared to enter human clinical trials for systemic use, representing an entirely new class of antibiotic drugs.

The first Phase I clinical trial will assess the safety of PMX-30063. The protocol for the study involves a dose-escalation study in healthy volunteers in which each subject will receive a single dose of PMX-30063. Upon successful completion of the first clinical study, PolyMedix plans to initiate a second clinical trial to mimic the expected clinical dosing regimen. The second trial, also to be conducted in healthy volunteers, will involve repeat dosing of two intravenous infusions per day, for five to seven days. Following these clinical trials, additional clinical studies and regulatory submissions will be required to obtain regulatory approval from the FDA and other regulatory bodies before PMX-30063 could be commercially sold.

"The clearance of the CTA for PMX-30063 represents a major milestone for PolyMedix," said Nicholas Landekic, CEO of PolyMedix. "This novel antibiotic compound represents a fundamental potential breakthrough in the world of infectious diseases. This is the first small molecule defensin mimetic to enter clinical development intended for the treatment of systemic infections, and the first and only such compound which is designed to directly address the growing problem of bacterial drug resistance. We are proud to be the first company to be developing this completely new type of antibiotic to address a major clinical need and market opportunity."

Completely different 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 will be the first small molecule mimetic of host defense proteins to enter clinical trials intended to treat systemic infections.

PMX-30063 and other PolyMedix antibiotic compounds have unique 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;
• 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 unique abilities 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 is unique among known antibiotic drugs. For this reason, 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 also support our view of a lower likelihood of developing resistance.

http://www.polymedix.com.