A doctors view on why controlled blood coagulation at the right time, in the right place, is vital

This blog introduces our current co-investment opportunity, Aplagon Oy, and was written by Riitta Lassila, Head of Coagulation Disorders Unit, Helsinki University Hospital and CSO of Aplagon Oy. Interested in investing together with us into a company transforming how blood clots are prevented ? Visit our co-investment platform and download the investor material.

 


 

Blood is an essential functional organ of the body; while in constant circulation, blood secures oxygen delivery to and the health of other organs, such as the heart, brain, lungs, gut and kidneys. The normal role of blood coagulation is to stop a bleed and heal a wound, thus maintaining life.

 

Blood and hemostasis

Intact blood vessels and their vascular surfaces in both arteries and veins allow timely healing action at the right spot upon an injury. This physiological system is called hemostasis, the first stage of wound healing, which is secured by a large number of tiny but highly functional platelets (150-300 million/milliliter of blood). Platelets adhere to vessel injury sites and interact with blood coagulation proteins to form networks of fibrin to further secure stable hemostasis. The outcome of hemostasis is to cease the tissue bleed, initiate healing and restore normal blood flow.

 

Thrombosis

Sometimes this physiological system overshoots, suddenly stopping blood flow by occluding an artery or vein, a phenomenon called thrombosis. Blood then coagulates inside the vessel, while in hemostasis this occurs outside the vessel at the site of the bleed. A severe organ failure, such as infarction and insufficiency of the brain, heart, gut and kidneys may result, compromising every-day life or even causing death.

These devastating thrombotic events may occur spontaneously, but mainly occur in association with diseases enhancing blood coagulation, such as diabetes, cancer or cardiovascular disease with sick vessel walls. The thrombotic events are prevented and managed with antithrombotic drugs that are antiplatelets (such as aspirin or ticagrelor) or anticoagulants (such as heparins, warfarin or novel dabigatran, rivaroxaban, apixaban and edoxaban).

To manage an already occurred thrombotic occlusion, fibrinolytic therapy (degrades the clot) and vascular interventions or surgery are often urgently needed, subjecting the patient to bleeding or thrombotic complications or even both, which may risk the success of the intervention.

 

Current management

The current management of the above disorders is based on systemic drugs, which expose the whole body to them, whereas the problem is and thereby its treatment should be local at the site of the intervention.

The challenge of surgery and intervention is the unavoidable injury to the vessel wall (the stiches, balloon and stent placement all exposing vascular collagen in the inner layers of the vessel wall) and the risk of inappropriate coagulation (thrombosis, bleed or poor healing).

Vascular surgery or interventions cannot be performed without an antithrombotic drug. Usually aspirin and/or heparin, both with systemic effect, are used to neutralize the propensity of intravascular blood clotting, which surgery induces mainly locally.

 

Clinical need for Aplagons APAC therapy

Instead of the current systemic therapies an antithrombotic drug working locally would be ideal to address the site-specific blood coagulation and hemostasis during interventions.

We at Aplagon have developed a novel therapy called APAC (a dual antiplatelet and anticoagulant) that has properties to meet these criteria. APAC mimics the body’s own mechanisms (mast cell derived heparin proteoglycans), consists of accepted drug components to create a novel heparin-albumin conjugate, targets and retains at the vascular injury site despite high blood flow conditions (when applied either locally or even systemically), and inhibits overshooting platelet and coagulation activity while still preserving hemostasis and healing.

The many severe bleeding and thrombotic complications, currently occurring in 5-50% of therapies directed to heart, brain or renal vessel occlusions, call upon novel solutions, especially in the high-risk patients. APAC has been shown in several animal models to prevent thrombosis but preserve hemostasis when administered locally at the vascular injury site associated with interventions. APAC has also been shown to target, i.e. find its way to the injury site when administered systemically.

An extensive toxicology program required by regulatory authorities, including repeated dosing of APAC, provides a significant safety margin for the doses shown to be effective in already tested animal models and for the doses designed to be tested clinically in humans.

By virtue of its unique characteristics, APAC’s strategy may benefit several vascular interventions in the future. The planning of clinical trials in the first indications is underway. If the initial clinical trials are positive, the clinical utility of APAC may be vast in the cardiovascular field.

–  Riitta Lassila

Head of Coagulation Disorders Unit, Helsinki University Hospital and CSO of Aplagon Oy

 

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