Notes from Rodman & Renshaw Healthcare Conference May 17
Heparin reversal
PMX-60056 has two potential uses:
1. Heparin reversal after surgical procedures; protamine is currently the only available compound for heparin reversal in orthopedic and cardiothoracic procedures. Protamine has many potential side effects.
2. Long-term prevention of blood clots; currently Low Molecular Weight Heparin (LMWH) is used for this - 12M people per year.
If serious bleeding occurs (1-4% of patients) or clinically significant bleeding (25%), there is no reversing agent available.
60056 addresses all the limitations of protamin today (listed in slide).
No intrinsic affect on blood clotting if more 60056 is administered than is needed to reverse heparin.
P1a and P1b studies have been done.
Currently two studies in progress.
In March started study to reverse Tinzaparin, double-blind, randomized placebo-controlled study
(Slide says it is a crossover study).
April started heparin range finding heparin reversal study.
Both studies should be finished by end of June
One additional P2 study to start in Q3, larger study in cardiothoracic surgery, expected to finish in early 2011.
Assuming adequate financing, by middle of 2011 expect to start
P3 pivotal trials for LMWH and regular heparin reversal.
These studies are all single dose trials, primary end point is clotting time at 30 minutes, long term follow up is 24 hours, which makes trials that are very rapid and inexpensive.
Antibiotic Market
PMX-30063
First target is serious hospitalized infections, particularly Gram+ drug-resistant that are treated with an intravenous drug.
Finished two phase 1 studies.
Expect to start phase 2 by end of June.
Resistance to mold and fungus derived antibiotics results from the requirement that the compound must cross the bacterial membrane to find their biochemical targets. Bacteria evolve resistance through efflux pumps and mutations of the target.
Plants and animals use host defense proteins (defensins) which target the bacterial membrane itself and create holes in the membrane. PMX-30063 is a synthetic defensin mimetic.
These defensins do not attack mammalian cells.
In resistance studies, there has been none even after 20 passages through trials with many different bacteria and several Polymedix compounds.
Estimating human dosage requirement from animal studies.
In animal studies where a single dose results in efficacy, the equivalent mg/kg in humans is estimated.
In P1a single-dose escalation MTD was 2.5 mg/kg.
In P1b multi-dose escalation over 5-10 days at Q48, 24, 12 hours.
Results: dosed up to 0.6 mg/kg x 5 days - 3.0 mg/kg total.
This is about 10 times what animal model says should be needed for full efficacy.
The only adverse event at highest doses were sensations of numbness and tingling, starting in the mouth, and at higher concentrations going to the fingers and toes.
This was mild, not disabling, transient, and resolved on its own after stopping the drug, no treatment was needed.
In study of several MRSA strains with blood drawn from patients given single dose of 0.1 to 0.3 mg/kg, there was full bactericidal activity. This correlates perfectly with the animal studies and suggests a dose of .15 to .25 and that we are able to dose about 10 times more drug in total.
By end of June hope to start P2 efficacy trials for broad treatment of all staph
- multiple doses
- finish Q1 2011
Middle of 2011, start pivotal trials, provided enough money is available.
Planning to apply for fast track for both drugs.
Finances
finished Q1 with $30M cash
Burn is $1M-$1.5M/month
Should be enough to finish all P2 studies and do all the P3 enabling work:
manufacturing, toxicology
60056 will always be a single dose drug
30063 should need only 5 days of therapy
so trials should be quick and inexpensive
Jason |
