1. EP217609 and avidin
Open-heart surgery - Phase 1
Endotis conducted three Phase I clinical studies with EP217609 and avidin. These studies, which enrolled more than 100 individuals, established that both compounds were well-tolerated and exhibited predictable pharmacokinetic and pharmacodynamic profiles in healthy subjects. In addition, they demonstrated that avidin inactivated EP217609 in vivo rapidly, completely and irreversibly.
The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of EP217609 were evaluated in 40 healthy volunteers. A stable, dose-related response was observed by measuring the Activated Clotting Time (ACT). The half-life of the product is ~20 hrs.
Importantly, in sharp contrast to heparin, there was a close parallel relationship between the pharmacokinetic and pharmacodynamic profiles of EP217609. Thus, the coagulation effect was very predictable, with low variability between subjects. As a result, it is possible to use a single uniform dose for all subjects.
EP217609 is not metabolized and is excreted primarily in the kidneys. There is no interaction with platelet inhibitors (i.e. Clopidogrel) and CY P450 isoenzymes
The pharmacokinetic profile of avidin was evaluated in 24 healthy volunteers. Avidin was well-tolerated, with a half-life of about 15 minutes. The compound has no pharmacologic activity in man.
The anticoagulation effect of EP217609 and its neutralization by avidin after 90 minutes (i.e. the average time of ECC during cardiac surgery) was studied in 36 healthy volunteers. Similar to the dog experiments, EP217609 produced a predictable, stable increase of the ACT, which was rapidly, completely and permanently reversed by the addition of avidin.
Open-heart surgery - Phase 2a
A Phase 2a in ECC during cardiac surgery has been initiated and is projected to be completed in 1H 2012. The goal of this proof-of-concept study is to evaluate 32 low-risk subjects treated either with heparin or with EP217609.
Open-heart surgery - Phase 2b
A Phase 2b in ECC during cardiac surgery is planned to start in 2H 2012. The goal of this dose finding study of 240 medium-risk subjects will be to identify the dose of EP217609 to use in a pivotal Phase 3 trial in order to show clinical superiority compared to heparin/protamine.
2. Oral Fondaparinux
Venous Thomboembolism Prophylaxis
The Company's partner, Catalent, has developed a formulation of fondaparinux with sufficient bioavailability to make the project commercially attractive.
Dose-dependent responses have been demonstrated in dog models. Catalent is finalizing pre-clinical activities to ensure that the product that will be tested in Phase 1 can be produced at commercial scale. A proof-of-concept Phase 1 trial is planned for 2011.
3. EP37
Stroke Prevention in Atrial Fibrillation (SPAF)
EP37 is a biotinylated, oral neutralizable anticoagulant that is in pre-clinical development. It is designed to allow rapid neutralization of the anticoagulant activity in case of emergency surgery or in medical situations that require it. The Company is open to partnering to rapidly advance the clinical development of this breakthrough compound.
Research & Development Programs
