PolyMedix Presents PMX-60056 Clinical Data at the American Heart Association Scientific Sessions Meeting
Two presentations focusing on novel anticoagulant reversing agent PMX-60056
RADNOR, Pa.--(BUSINESS WIRE)--Nov 15, 2010 - PolyMedix, Inc (OTC BB: PMYX), an emerging biotechnology company focused on developing new therapeutic drugs to treat life-threatening infectious diseases and acute cardiovascular disorders, announced that data from two Phase 1B/2 clinical studies with PMX-60056 were presented today, in oral and poster sessions, at the Annual American Heart Association Scientific Sessions Meeting. PMX-60056 is a synthetic, small-molecule designed to reverse the anti-clotting effects of both heparin and low molecule weight heparin (LMWH).
“We are encouraged by the fast, permanent and complete reversal of the anti-clotting effects of heparin and low molecular weight heparin demonstrated by PMX-60056 in these studies,” commented Dr. Eric McAllister, Vice President of Clinical Development and Chief Medical Officer at PolyMedix. “PMX-60056 restored blood clotting times to the normal range even before administration of the ten-minute infusion was completed. We look forward to continuing the development of PMX-60056 and advancing into a phase 2 clinical study.”
Heparin Reversal Clinical Results
In an oral presentation, “Heparin-Antagonist PMX-60056 Rapidly and Completely Reverses Heparin Anticoagulation in Man,” Dr. Eric McAllister reported on results from a Phase 1B/2 double-blind, placebo-controlled crossover clinical trial in six healthy male subjects. On two occasions separated by a 2-day washout period, each of the six subjects received a prophylactic dose of unfractionated heparin as an intravenous bolus, followed 20 minutes later with either PMX-60056 or placebo as a ten-minute intravenous infusion. Coagulation was assessed by two standard measurements of blood clotting time, activated clotting time (ACT) and activated partial thromboplastin time (aPTT).
All (6 of 6) subjects receiving PMX-60056 demonstrated rapid and permanent reversal of the anticoagulation effects of heparin, while none (0 of 6) demonstrated reversal after receiving placebo. The reversal seen in subjects receiving PMX-60056 was complete before the end of the infusion period, which suggests that less than the 0.3 mg/kg dose used may be required to neutralize 70 U/kg of heparin. The restoration of blood clotting seen with administration of PMX-60056 was permanent. For subjects receiving placebo, heparin was eliminated over a 4-hour period, as expected from known pharmacokinetics.
Low Molecular Weight Heparin Reversal Clinical Results
The poster presentation, “Heparin Antagonist PMX-60056 Rapidly Reverses Anti-Xa and aPTT Effects of Tinzaparin in Man” reported on a Phase 1B/2 double-blind, placebo-controlled crossover clinical trial in six healthy male subjects. On two occasions separated by a 2-day washout period, each of the subjects were given a subcutaneous injection of the standard prophylactic dose (175 IU/kg) of the LMWH, tinzaparin. Five hours later, which was the time of the expected maximum anticoagulation, each subject received either 0.3 mg/kg PMX-60056 or placebo as a 10-minute intravenous infusion. Three hours later, the same dose of drug was infused again to neutralize the additional tinzaparin still entering the blood stream from the subcutaneous delivery site.
The results showed that PMX-60056 rapidly reversed prophylactic doses of tinzaparin, demonstrating both reversal of anti-Xa activity and normalization of blood clotting times (measured using both ACT and aPTT). The effect was complete before the end of each ten-minute infusion period.
The degree of reversal was relatively constant at 0.4 anti-Xa units/mL, even though the peak anti-Xa effect of tinzaparin ranged from 0.4 to 1.0 IU/mL in subjects. Despite the resumption of anticoagulation from continued delivery of tinzaparin from the depot administration, PMX-60056 reversed the aPTT to normal by the end of each of the two infusion periods. The study also found mean systolic/diastolic blood-pressure reductions of 21/17 mmHg. These small reductions in blood pressure were almost certainly due to excess PMX-60056 remaining after all available tinzaparin had been matched. No important side effects were observed in the study.
There is no FDA approved reversing agent for LMWHs. PMX-60056 may allow the expanded use of LMWH in thrombogenic medical or surgical procedures that require rapid reversal of anticoagulation afterward, as well as for treatment of bleeding in patients taking long-term LMWHs.
“We believe PMX-60056 offers the potential to advance the management of coagulation in the use of heparin and low molecular weight heparins, both in routine surgical procedures and in cases of bleeding complications,” commented Nicholas Landekic, President and CEO of PolyMedix. “Our clinical results may have shown for the first time, an agent's ability to fully normalize blood clotting time after the administration of a low molecular weight heparin. These data represent significant milestones for PolyMedix, and further validation of our rational drug design platform.”
PolyMedix's heptagonist compound, PMX-60056, is a synthetic, small-molecule designed to reverse the anticoagulant activity of both heparin and low molecular weight heparins (LMWHs). Heparin is an intravenous anticoagulant used to prevent clots from forming during certain cardiothoracic and orthopedic surgical procedures. After these procedures, the anticoagulant activity of heparin is reversed in order to prevent post-operative bleeding. Protamine is presently the only agent available for this use. Protamine has many limitations, and we believe there is a major need for alternative heparin reversing agents which may be safer or easier to use. LMWHs are used in approximately 12 million patients annually for chronic treatment of thrombosis. Up to 20% of patients may experience bleeding complications. There is presently no FDA approved agent available to reverse the anticoagulant activity of LMWHs. PolyMedix believes PMX-60056 pre-clinical and clinical data suggest potential safety and other advantages over protamine, as well as an opportunity to be the first reversing agent for LMWHs.
About PolyMedix, Inc.
PolyMedix is a publicly traded biotechnology company focused on the development of novel drugs for the treatment of serious infectious diseases and acute cardiovascular disorders. PolyMedix uses a rational drug design approach to create non-peptide, small-molecule drug candidates. PolyMedix's lead antibiotic compound, PMX-30063, is currently in Phase 2 clinical trials. PMX-30063 is a small-molecule that mimics the mechanism of action of human host defense proteins, a mechanism that is distinct from currently approved antibiotic drugs and is intended to make bacterial resistance unlikely to develop. PolyMedix plans to develop this compound for serious systemic Staphylococcal infections, including methicillin resistant Staphylococcus aureus (MRSA). PolyMedix's lead heptagonist compound, PMX-60056, has completed Phase 1 testing and is being developed to reverse the anticoagulant activity of both heparin and low molecular weight heparins (LMWH). PolyMedix believes that PMX-60056 could potentially be a safer and easier to use anticoagulant reversing agent, with broader activity, than the currently approved therapy for reversing heparin and LMWH. In addition to its small molecule therapeutics, PolyMedix has polymeric formulations with the same mechanism of action as PMX-30063, PolyCides™, which are intended for use in antimicrobial biomaterials applications such as additives to paints, plastics, and textiles to create self-sterilizing products and surfaces.
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 that involve risks, uncertainties and assumptions that could cause PolyMedix's actual results and experience to differ materially from anticipated results and expectations expressed in these forward looking statements. PolyMedix has in some cases identified forward-looking statements by using words such as “anticipates,” “believes,” “hopes,” “estimates,” “looks,” “expects,” “plans,” “intends,” “goal,” “potential,” “may,” “suggest,” and similar expressions. Among other factors that could cause actual results to differ materially from those expressed in forward-looking statements are PolyMedix's need for, and the availability of, substantial capital in the future to fund its operations and research and development, and the fact that PolyMedix's compounds may not successfully complete pre-clinical or clinical testing, or be granted regulatory approval to be sold and marketed in the United States or elsewhere. A more complete description of these risk factors is included in PolyMedix's filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. PolyMedix undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events, except as required by applicable law or regulation.
Posted: November 2010