PolyMedix, Inc.(fka PYMXQ)

[gandalf2325]

HansG, you are right that 30063 is broad-spectrum and has activity against both gram-negative and gram-positive bacteria. But, it does not have activity against all types of bacteria (there are a few somewhat prominent gram negative strains that it does not likely have much activity against at currently tested dosing levels). 30063 is specifically tailored for activity against staph aureus - which is the largest potential antibiotic market and the reason it was picked to proceed through the clinic first. Although, importantly for marketing purposes, it does shows a much broader spectrum of activity than daptomycin, linezolid and vancomycin which are just effective against certain gram-positive bacteria.

I believe Polymedix will be able to complement 30063 by creating other non-peptidic defensin mimetics that are chemically structured for better efficacy against some of the other medically relevant bacteria out there, although likely at the expense of activity versus staph aureus. For instance, it does not appear 30063 can be administered at high enough dosage levels to show efficacy against gram-negative Pseudomonas aeruginosa (ie no therapeutic window). See the following link for info on Multidrug-Resistant Pseudomonas aeruginosa. Against some of the other medically important bacteria (Acinetobacter, S. pneumoniae, Viridans group streptococci, P. mirabilis, A. baumanii) 30063 has mixed levels of activity, but in total none of them are as susceptible to 30063 as staph aureus is.

Some of these bacteria comprise smaller markets and could be met with new HDP mimetics that are approved under some of the newly discussed limited market regulatory initiatives. But if there was a 30063 companion drug that showed broad activity against a few of the larger market gram-negative bacteria that 30063 was less effective against it could also be a very big seller and a nice complement to 30063 in mankind's arsenal against the superbugs. Hence the reason I included that in the Other Opportunities section. Polymedix management have mentioned that this is in their plans as well...

You can peruse the presentations on the company website to see which specific bacteria 30063 will potentially be effective against:
ICAAC 2008 In Vitro see slide 6 and 7
Superbugs 2009 slide 11
ECCMID 2011 Gram+ Gram- Activity
ECCMID 2012 Staph Strep Activity
IDSA 2011 In vitro Ex vivo activity
ICAAC 2010 Structurally Diverse HDP Mimics

As a note on how I am interpreting the MIC data from the above presentations. Cmax (maximum plasma concentration) appears to be the most important factor for efficacy for 30063 and likely other HDP mimetics due to long half-life and short time required for bactericidal activity. The 1.0 mg/kg dose level in the Phase I gave a Cmax of about 16 ug/ml. It will likely be necessary to have Cmax be at least 2xMIC for a cure and 4xMIC maybe being a better number. So for a bacteria with a 30063 MIC of 16 ug/ml, a single dose of 1.0 mg/kg would very likely not be enough. A MIC of 8 ug/ml might be considered the upper end for efficacy and anything at or below 4 ug/ml should be considered very susceptible to 30063 at single dose levels of 1.0 mg/kg. We do not know yet what the highest Cmax they will be able to safely administer, so none of this is much more than an educated guess at this point. Although, we do know the Cmax they achieved in all dosing arms of the Phase 2 is more than enough for staph aureus as shown by the efficacy and flat dose response curve in the latest Phase 2 trial, which is the important thing for 30063 and PYMX investors at this point.