Pipeline

In its therapeutic programmes, Ablynx has adopted a progressive strategy for target selection, lead generation, pre-clinical and clinical development. This strategy is designed to fully exploit the known advantages of Nanobodies^®, including their cavity binding property and their ability to act in a bi-specific or bi-functional fashion. In addition, because of their exceptional stability, solubility, and small size, Nanobodies^® have the potential to be specifically formulated for a number of therapeutic areas including gastrointestinal, respiratory and dermal indications.

ALX-0081 (anti-vWF Nanobody^®)

Cardiovascular disease, including acute coronary syndrome (ACS) and stroke, remains the leading cause of death in western societies despite improvements in prevention, detection, and treatment. It is caused by a narrowing or blockage of the arteries due to thrombus formation on ruptured atherosclerotic plaques, preventing enough blood reaching the heart or brain. Almost 1 million Americans die of cardiovascular disease each year, which adds up to 42% of all deaths.  ACS consists of myocardial infarction (MI), as well as stable and unstable angina, of which MI is the most frequently occurring indication. Currently the treatment of ACS patients consists of a mixture of different anti-thrombotic drugs. These drugs are limited in their capability to prevent arterial thrombosis and are associated with a high percentage of drug non-responsiveness and bleeding complications.

Ablynx’s lead development programme, ALX-0081, is a therapeutic Nanobody^® targeting von Willebrand Factor (vWF), which will reduce the risk of thrombosis in patients with acute coronary syndrome (ACS) and thrombotic thrombocytopenic purpura (TTP). The drug has completed phase I in healthy volunteers. The results of the double-blind, placebo controlled study in 40 healthy male volunteers show that ALX-0081, was safe and well tolerated at all doses tested, with no dose limiting toxicities or serious adverse events. Following these positive Phase I results, Ablynx will now progress ALX-0081 to a multi-dose study during 2008. In the study, treatment with the Nanobody^®did not result in detectable immunogenicity. The study suggests that ALX-0081 adopts at least the plasma half-life of the target, vWF. The expected anti-thrombotic activity was shown with a biomarker in all volunteers receiving at least 2 mg of ALX-0081, indicating the high potency of the drug. ALX-0081’s pharmacological activity, based on a single injection, started at the lowest dose of 2 mg and reached a maximum duration of 12 hours at a dose of 12 mg.

Through its novel, highly selective mode of action, ALX-0081 effectively prevents arterial thrombosis, without interfering with the desired haemostatis (wound heeling) in the patient which results in less bleeding complications. Pre-clinical in vivo and clinical studies confirm that ALX-0081 has the unique potential to set a new standard in anti-thrombotic therapy based on its immediate onset of action, its ultra-high potency and significantly improved safety compared to the currently marketed therapies in the form of dramatically reduced bleeding complications. Ablynx has demonstrated an impressive therapeutic window for ALX-0081 based on the high efficacy and low bleeding demonstrated in primate studies, resulting in a highly attractive drug profile.

Besides the primary indication ACS and TPP, another relevant indication for ALX-0081 is ischemic stroke. It is estimated that each year more than 700,000 people suffer from stroke in the US only, resulting in 280,000 mortalities each year.