Phase 1B clinical study with PMX-60056 meets safety and efficacy endpoints: PolyMedix

PolyMedix, Inc. (OTC BB: PYMX), an emerging biotechnology company focused on developing new therapeutic drugs to treat acute cardiovascular disorders and infectious diseases, has successfully completed a second Phase 1B clinical safety and pilot efficacy study with PMX-60056, a small synthetic molecule designed to reverse heparin and low molecular weight heparin (LMWH) anticoagulants. The data from this study show that PMX-60056 met the study safety and efficacy endpoints regarding the reversal of the anticoagulant activity of the LMWH tinzaparin.

“We believe bleeding complications associated with LMWHs represent a major unmet medical need for a new reversing agent”

Highlights from the Phase 1B clinical study

• PMX-60056 neutralized the anticoagulant activity of LMWH tinzaparin
• PMX-60056 normalized blood clotting time
• PMX-60056 was safely administered in humans with no serious adverse events occurring in the study

"To our knowledge, no other drug has been able to effectively reverse the anticoagulation activity of LMWHs," commented Dr. Eric McAllister, Vice President, Clinical Development and Chief Medical Officer of PolyMedix. "We believe that PMX-60056 could potentially address an important unmet medical need as a reversing agent for LMWHs."

The Phase 1B double-blind, placebo-controlled, crossover study was conducted at a single site in the United States. Six healthy subjects were randomized into two cohorts and given a subcutaneous injection of tinzaparin (Innohep^®), an FDA approved LMWH to prevent the formation of blood clots. Subjects received a ten-minute intravenous infusion of PMX-60056 or placebo at 5 and 8 hours after administration of tinzaparin. With the crossover design, on the second treatment day, each subject received the alternate treatment, therefore, those that received PMX-60056 received placebo and vice versa. Thus, each subject served as his or her own control.

Safety

PMX-60056 was well tolerated in this study, with no serious or reportable adverse events occurring. Subjects in the study experienced minimal side effects which consisted of mild itching or warmth lasting only minutes, and brief reductions in blood pressure. Protamine, the only agent currently approved to reverse heparin, is not approved for the reversal of LMWH, both because it is not able to completely reverse LMWH activity, and also because of the potential for significant blood pressure reductions. In this study with PMX-60056 changes in blood pressure were transient and not clinically relevant when LMWH was present, as shown in the graph below of mean systolic and diastolic pressures.

(See Multimedia Gallery for Graphs.)

Efficacy

To measure the efficacy of PMX-60056 in reversing tinzaparin, anti-Xa activity in the blood (a critical clotting factor) was assessed, and reversal of blood clotting time was measured by activated partial thromboplastic time (aPTT), a laboratory measurement of blood clotting time. As indicated in the charts below, after the first ten-minute infusion of PMX-60056, anti-Xa activity and aPTT were reduced. As administered in the study, the tinzaparin continued to enter the subjects' systems from the subcutaneous injection site, and as it did so, anticoagulation returned. A second ten-minute infusion of PMX-60056 three hours later showed similar results.

(See Multimedia Gallery for Graphs.)

LMWHs are widely used to prevent the formation of blood clots in patients with deep vein thrombosis, receiving cancer treatment drugs, or after hip replacement surgeries and heart attacks. Despite the benefits of LMWHs, up to 20% of patients may experience bleeding complications during therapy. With no FDA approved product available to reverse the anticoagulant activity of LMWHs, many of these patients may require life-saving surgery or blood transfusions to treat their bleeding complications.

"We believe bleeding complications associated with LMWHs represent a major unmet medical need for a new reversing agent," commented Nicholas Landekic, President & C.E.O. of PolyMedix. "There is no approved reversing agent for LMWH. We believe that PMX-60056 is unique in being the first and only reversing agent in development designed to reverse the anticoagulant activity of both unfractionated heparin and LMWH. This study has shown that PMX-60056 has the potential to offer important benefits and improvements in treating these patients at risk of bleeding complications."

LMWHs, like heparin, contain pentasaccharide, a chemical sequence that is essential for their anticoagulation activity. The pentasaccharide in LMWH and heparin binds with antithrombin, which then turns off the normal blood clotting process. PMX-60056 is designed to reverse the anticoagulation activity by binding to the pentasaccharide sequence on both heparin and LMWH and disrupting the interaction with antithrombin. As a result, normal blood clotting ability is restored.

In October 2009, PolyMedix successfully completed a similarly designed study in six healthy subjects that had received heparin and PMX-60056. The results showed that a single dose of PMX-60056 was well tolerated, and met the study efficacy endpoint regarding reversing heparin and normalizing blood clotting time. An additional Phase 1B clinical trial is also currently underway with PMX-60056, a dose-range finding study to further characterize reversal of heparin. PolyMedix expects to complete enrollment in this study this quarter and announce results during the third quarter of 2010. PolyMedix also plans to initiate a Phase 2 clinical trial in surgery patients during the second half of this year.