PMX-30063

“Our infectious disease program at PolyMedix is dedicated towards developing innovative, first of their kind therapies that are effective against today’s infections, without making the infections of tomorrow more difficult to treat”

PMX-30063 is our most advanced compound and the first in a new class of antibiotics - defensin-mimetics - which are intended to address the global problem of bacterial resistance. PMX-30063 is a unique antibiotic agent designed to mimic one of the body’s first lines of defense against bacteria (host defense proteins). Host defense proteins kill bacteria by forming pores in (physically puncturing) the bacterial cell membrane. By mimicking this mechanism, PMX-30063 exploits a method of bacterial cell killing that significantly reduces the risk for emergence of resistance. In addition to its unique resistance profile, PMX-30063 has shown rapid bactericidal activity against many Gram-positive and Gram-negative pathogens including methicillin-resistant Staphylococcus aureus (MRSA), drug resistant Enteroccus, E. coli, and NDM-1 drug-resistant Klebsiella pneumonia.

PMX-30063 has completed enrollment in a Phase 2 clinical trial to treat patients with acute bacterial skin and skin structure infections (ABSSSI) caused by Staphylococcus aureus, including MRSA. Interim results from this on-going study suggest both efficacy and safety in treating Staph infections.

Our current plan is to initially seek FDA approval for an intravenous (IV) formulation of PMX-30063 in treating patients with ABSSSI. In the future, we plan to conduct additional clinical studies of PMX-30063 in patients with other infections, such as blood stream infections, lung infections and oral mucositis.  We also intend to evaluate other routes of administration beyond IV.

Unmet Medical Need

Bacterial drug resistance to presently available antibiotics is one of the most serious global healthcare problems which has reached alarming levels with 70% of infections treated in hospitals being resistant to at least one antibiotic drug. A recent analysis of antibiotic resistant infection data conducted at Chicago Cook County Hospital estimated that the societal annual cost to the United States health care system for antibiotic resistance is in excess of $35 billion. With the emergence of more drug-resistant strains of bacteria and the increased incidence of drug-resistant infections, the need for novel therapies to fight these infections is more urgent than ever. There are many antibiotics in development for treatment of resistant bacterial infections. Since these antibiotics are generally derivatives or new generations of conventional antibiotics, resistance is likely to evolve to these new antibiotics as well, making future infections even more difficult to treat.

While the use of conventional antibiotics has saved many lives, a significant disadvantage to their use is that bacteria can readily and rapidly mutate in ways that render these conventional antibiotics ineffective or drug resistant. This may explain why as more advanced forms of life evolved, this approach was abandoned and replaced with more robust defenses to which bacteria are less likely to resist, including host defense proteins. Host defense proteins are part of the innate immune system. In the human body, host defense proteins represent a first line of defense against bacterial attack and primarily exist in the respiratory tract, urogenital tract, gastrointestinal track and epidermal tissues under the skin, all locations where microbial pathogens first enter the human body. Host defense proteins use a simple, but effective method for killing bacteria by targeting bacterial membranes and creating an instability of the cellular contents and membrane, which results in the rapid killing of the bacterial cell. Resistance to this mechanism of action has not developed despite hundreds of millions of years of evolution.

Market Opportunity

According to IMS Health, the total United States sales of the five antibiotics labeled for MRSA doubled from 2005 to 2009 to $1.5 billion. Sales of linezolid and daptomycin account for 75% of these sales with the most prescribed MRSA labeled drug being generic vancomycin.

PMX-30063 appears to have favorable features compared with the leading approved classes of antibiotics used to treat MRSA, as shown in the chart below: