• The Need:
Bacterial drug resistance is emerging as one of the most significant problems - and commercial opportunities - in medicine. This problem has arisen from many years of over-use and misuse of antibiotic agents, such as inappropriately trying to treat viral infections with antibiotics, and adding antibiotics to animal feed. Further, until very recently there has been a lack of pharmaceutical research into novel classes of antibiotic agents. The incidence of drug-resistant hospital infections is growing at an alarming rate, and strains of bacteria are now emerging that are resistant to all known antibiotic drugs.

Each year, an alarming 2,400,000+ nosocomial infections (acquired in healthcare facilities while undergoing treatment for another ailment or illness) occur in the U.S. alone. They are estimated to directly cause 30,000 deaths and contribute to another 70,000 deaths each year, over 100,000 deaths annually in total - the fourth leading cause of death in the U.S. Nosocomial infections can directly cost over $30,000 per incident and account for $4.5 billion annually in total extended care and treatment (Source: U.S. Centers for Disease Control).

• The News:
The pharmaceutical industry is now in a "catch-up" mode and feverishly attempting to discover new types of antibiotic drugs. However, most of this work is focused on synthesizing analogs of known drugs (such as cephalosporins and quinolones), which, while potentially useful for a short time, will inevitably also encounter drug resistance. The worldwide human therapeutic markets for anti-infective drugs exceeds $25 billion, and offers tremendous commercial opportunities.

PolyMedix uses a proprietary computational de novo drug design platform to design biomimetics: small molecules that mimic the activity of proteins. The first products developed using the computational platform are novel small molecule antibiotic drugs which mimic the activity of host defense proteins. These compounds are also called BAAC’s – Bactericidal Amphiphilic Antibiotic Compounds. We believe these are the first and only small molecule defensin mimetics being developed intended for use in systemic infections. These compounds mimic the mechanism of action of the host defense proteins. From a small library of a few hundred compounds, a high hit rate of biologically active compounds was produced and the first clinical IND candidate, PMX-30063, has been selected. These have broad and potent antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria, including antibiotic-resistant. Our compounds:

• Show potent and broad spectrum, active against over 150 Gram-positive and Gram-negative human pathogens;
• Are active against drug-resistant bacteria including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococcus (VRE).
• Are rapidly bactericidal, killing bacteria in a matter of minutes
• Are selective for bacterial cells versus mammalian cells
• Demonstrate antifungal and antiviral activities in addition to antibacterial
• Are simple and inexpensive to synthesize
• Have molecular weights between 500 to 1000 D.
• Show robust activity in animal models of bacterial infection with activity comparable to superior to vancomycin
• Indicate that bacterial resistance has not been observed in serial passage studies.

By mimicking the activity of the host defense proteins, PolyMedix’s compounds have a highly unique mechanism of action: directly lysing bacterial cell membranes, resulting in the destruction of the genetic machinery often responsible for bacterial resistance. Thus, it is unlikely that bacterial resistance can easily develop to these compounds. The overall approach has been the design of biomimetic polymers, oligomers, and small molecules that 1) mimic key biological properties of proteins and 2) are more stable and inexpensive to produce than natural proteins. The first application of this technology has been the design and synthesis of non-peptide mimetics of host defense proteins that exhibit potent and broad spectrum anti-microbial activity.

Serial passage experiments demonstrate that bacterial resistance does not easily develop to the Polymedix compounds:

We believe PolyMedix compounds have potency comparable or superior to reference antibiotic drugs, with potent activity against drug-resistant bacterial strains. By offering a low likelihood of drug resistance, these compounds directly address the greatest unmet need in anti-infective therapy. As a result, these drug candidates offer a significant opportunity, and the possibility to become the standard of care for hospital infections.

• The Status:
We received a notice of no objection letter 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.

We are also evaluating our antibiotic compounds for a number of other topical applications, including use for ophthalmic infections, skin structure infections, oral healthcare applications for treatment of periodontal disease, topical treatment for ear infections, topical treatment of fungal infections, as well as topical treatment of acne.

Efficacy vs. vancomycin in the rat thigh burden model
PMX-30063 and PMX-30016 are equally or more efficacious than vancomycin

Maximum efficacy (˜99.999% bacterial cell killing) achieved at total doses of 2-4 mg/kg

Efficacy PMX-30063 and PMX-30016 Mouse Sepsis Model: S. aureus infection
PolyMedix compounds are highly active in mouse peritonitis/sepsis model

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