Cyclodextrins

Cyclodextrins (CDs) are cyclic sugar molecules containing six, seven or eight glucose units, giving rise to α‐, β- , and γ- cyclodextrin, respectively. Addition of specific moieties to this sugar ring create cyclodextrins with specific properties.

These modified cyclodextrins are used in a variety of applications including pharmaceuticals (excipients). As such this class of molecules is well described and are in general very safe.

Pro-coagulant cyclodextrins
3D structure
of OKL-1187

By means of state-of-the-art technologies, a series of highly procoagulant cyclodextrins were discovered and optimised for potential treatment of bleeding. These proprietary cyclodextrins accelerate coagulation in vitro and in vivo but, importantly, do not initiate coagulation. As such they provide a fast and safe option to stop bleeding in a variety of conditions.

The cyclodextrin pro-coagulants may have many applications in the treatment or prevention of bleeding, including haemophilia, trauma, surgery, and bleeding related to the use of anti-coagulants. Alveron is currently focussing on the development of a universal anticoagulant reversal agent.

Therapeutic area

Anticoagulants are the mainstay of therapy for the acute and long-term prevention and treatment of numerous types of thromboembolic disorders. The prevention of thromboembolic stroke among patients with chronic atrial fibrillation (AF) is one of the primary indications for oral anticoagulation therapy. In addition, anticoagulants are indicated in, and are increasingly prescribed for the prevention and treatment of, venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). Vitamin K antagonists, unfractionated heparin, low-molecular weight heparins, direct thrombin inhibitors, and factor Xa inhibitors are critical for the treatment and prevention of these disorders. Anticoagulant therapy is inevitably associated with a risk for bleeding and these bleeding complications can be life-threatening. Among patients who suffer anticoagulation-related major bleeding, the mortality rate is as high as 13%.

 

The choice of anticoagulation-reversal method currently depends upon the pharmacology of the agent, clinical urgency, and the severity of the bleeding. For several commonly used anticoagulants no, or no easy to use reversal agent or protocol is available which seriously limits the use of these drugs

 

Alveron’s proprietory cyclodextrins enhance coagulation in anticoagulant treated human plasma and blood in laboratory assays. The compounds are able to reverse the anticoagulant effects of currently used direct-acting oral anticoagulants (DOACS), vitamin K antagonists, platelet inhibitors, (low molecular weight) heparins and heparin-like compounds.  In mouse and rat models the compounds demonstrated fast and complete reversal of direct-acting oral anticoagulants. Moreover, preliminary safety studies indicate that the compounds do not elevate parameters associated with coagulation or thrombosis in the absence of bleeding.

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The Netherlands

 

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