Science

CLINICAL RESULTS

The Company conducted three Phase 1 clinical studies and one phase 2a study with the IV formulation of REG1. The phase 1 studies, which enrolled more than 170 individuals, established REG1 was well-tolerated, exhibited predictable pharmacokinetics and demonstrated the anticipated pharmacodynamic effects in both healthy volunteers and patients with cardiovascular disease.  The phase 2a study demonstrated the feasibility of replacing unfractionated heparin with REG1 in elective PCI.

Regado-1a was a volunteer-blinded, placebo-controlled dose-escalation study.  85 healthy volunteers were randomized to receive a dose of the anticoagulant RB006 or placebo, followed several hours later by a dose of the active control agent RB007 or placebo.  The study showed RB006 and RB007 were well-tolerated.  In volunteers treated with RB006, rapid and dose-dependent anticoagulation was observed.  This intended anticoagulant effect was stable for several hours.  In volunteers treated with RB006 who were then administered RB007, the anticoagulation was reversed rapidly and durably, returning their blood to its normal state.  This study demonstrated for the first time the anticoagulant activity of RB006 and reversal activity of RB007 in humans and that both agents are well-tolerated by healthy volunteers.

Regado-1b was a multi-center, double-blind, placebo-controlled study that enrolled 50 patients with stable cardiovascular disease taking commonly prescribed oral antiplatelet drugs like aspirin and Plavix™.  Patients were randomized to receive one dose of RB006 or placebo, followed several hours later by a dose of RB007 or placebo.  Again, the reversible anticoagulant activity of the REG1 system observed in Regado-1a was observed in Regado-1b, demonstrating the REG1 System works as expected in the target patient population.  This study also showed RB006 and RB007 were well-tolerated in patients on antiplatelet therapy, demonstrating the safety of REG1 in the target patient population.

Regado-1c was a double-blind, placebo-controlled study that randomized 39 healthy volunteers to receive three consecutive aptamer-control agent treatment cycles or placebo.  In patients receiving RB006, the dose was adjusted relative to body weight, and this dosing strategy delivered very reproducible anticoagulant effects.  Two groups of volunteers were dosed with RB006 on different treatment days and then assigned to varying doses of RB007 to establish the ability of RB007 to produce a range of therapeutic anticoagulant effects.  Regado-1c demonstrated that not only could RB007 neutralize completely the activity of RB006, but by adjusting the RB007 dose, physicians can titrate the anticoagulant effect produced by RB006.

REVERSAL-PCI was a multi-center, open-label, randomized Phase 2a study comparing the REG1 System to unfractionated heparin in patients undergoing elective percutaneous coronary intervention (PCI).  The study was designed to determine if RB006 could support the conduct of PCI as the sole anticoagulant and whether RB007 could facilitate planned femoral sheath removal in patients at low risk for complications associated with therapy-related bleeding or heart attack. The study enrolled 26 patients at sites throughout the US and Argentina.   All PCI procedures were successfully completed, with no signs of intraprocedural thrombotic complications.  In addition, the study showed that RB007 use was well tolerated in this patient population, and could be used to facilitate planned femoral sheath removal.  Finally, the study showed that the anticoagulant effect of RB006 and reversal of this effect by RB007 could be monitored using standard point of care coagulation measures such as the activated clotting time (ACT).