Dilaforette AB

The Challenge

Severe malaria kills close to one million people annually and infects 250 million. In severe malaria, parasitized red blood cells block blood vessels, which gives rise to reduced blood flow to vital organs such as the brain. There is no specific therapy available to reverse or prevent this mechanical blockage.

The malaria parasite Plasmodium falciparum  frequently gives rise to severe disease when parasitized erythrocytes bind and block capillaries in extremities or vital organs. One of the main causes of disease pathology and severity is hampered blood flow and associated reduced oxygen delivery with subsequent tissue damage. Blockage of the blood flow is due to the fact that parasitized erythrocytes adhere in the microcirculation: they bind both to the vascular endothelium (cytoadherence) and to uninfected erythrocytes (rosetting).

Dilaforette's Solution

Dilaforette has created new a low anticoagulant heparin derivative , sevuparin, for the treatment of severe malaria patients. Heparin has been successfully tried as an adjunctive treatment in severe malaria, but the use was discontinued due to severe bleeding complications related to its anticoagulant property.  Heparin is known from in vitro studies, however, to reverse the processes that lead to blockage of the blood flow. In Dilaforette's heparin analogues the anticoagulant activity of heparin has been significantly reduced, which strongly reduces this important risk factor.  Dilaforette is developing the first potential adjunctive treatment for severe malaria that prevents and reverses the ability of the parasitized red blood cells to block blood vessels.

Competitive advantages

For severe malaria there is no effective treatment. Due to its low anticoagulant activity, Dilaforette’s drug candidate can be administered with a more than tenfold reduction in the risk of prolonged bleeding compared to heparin.

Market

The introduction of artemisinin-based therapies has revolutionized the care of patients with malaria, but severe disease still claims up to 1 million lives annually according to latest figures, and a proportion remain neurologically disabled after an episode of cerebral malaria. It is estimated that mortality in severe malaria in African children is around 10% based on the numbers in the AQUAMAT trial with protocolized treatment, and probably higher in other settings. The total numbers of severe malaria cases are estimated to be around 10 million per year^1,2,3.