Ablynx today announced positive interim results from the ongoing Phase I study of its lead development programme, ALX-0081, an anti-thrombotic treatment. ALX-0081 is a novel ‘first-in-class’ therapeutic Nanobody® targeting von Willebrand Factor (vWF), which can reduce the risk of thrombosis in patients with acute coronary syndrome.
GHENT, Belgium | July 2, 2007 | Ablynx today announced positive interim results from the ongoing Phase I study of its lead development programme, ALX-0081, an anti-thrombotic treatment. ALX-0081 is a novel ‘first-in-class’ therapeutic Nanobody® targeting von Willebrand Factor (vWF), which can reduce the risk of thrombosis in patients with acute coronary syndrome.
The Phase I study in healthy volunteers is designed to assess safety, tolerability and pharmacokinetics of ALX-0081. It will also analyse pharmacodynamic effects of ALX-0081 to confirm its high potency. It is a double-blind, placebo-controlled trial in healthy male volunteers at a single center in Europe.
The study was initiated during the first quarter of 2007. The interim analysis indicates:
— the desired pharmacodynamic effect was observed as anticipated indicating the high potency of ALX-0081
— ALX-0081 was well tolerated and showed no serious adverse effects or dose limiting toxicity
The final results are anticipated to be available by the end of September 2007.
Dr Edwin Moses, CEO and Chairman said: “We are very encouraged by the positive results of our first Nanobody® in clinical development which is believed to be the first ever single domain antibody human trial. This is a significant milestone for Ablynx and demonstrates the success of Ablynx’s powerful discovery platform.”
About ALX-0081
Through its novel, highly selective mode of action, ALX-0081 is intended to prevent arterial thrombosis, without interfering with the desired haemostatis (wound healing) in the patient which results in less bleeding complications. Pre-clinical in vivo studies confirmed Ablynx’s belief that ALX-0081 has unique potential to set a new standard in anti-thrombotic therapy based on its immediate onset of action, its high potency and significantly improved safety compared to the currently marketed therapies in the form of significantly reduced bleeding complications. Ablynx has demonstrated a large therapeutic window for ALX-0081 based on the high efficacy and low bleeding demonstrated in primate studies, indicating a highly attractive drug profile.
About ACS
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.
Besides the primary indication ACS, 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.
About Nanobodies®
Nanobodies® are a novel class of antibody-derived therapeutic proteins. Because of their small size, unique structure and extreme stability, Nanobodies® combine the advantages of conventional antibody therapeutics with the key features of small-molecule drugs.
Nanobodies® are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies. The Nanobody® technology was originally developed following the discovery that camelidae (camels and llamas) possess fully functional antibodies that lack light chains. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Importantly, the cloned and isolated VHH domain is a perfectly stable polypeptide harbouring the full antigen-binding capacity of the original heavy-chain antibody. These newly discovered VHH domains with their unique structural and functional properties form the basis of a new generation of therapeutic antibodies which Ablynx has named Nanobodies®.
Ablynx’s Nanobodies® combine the advantages of conventional antibodies with important features of small molecule drugs. Like conventional antibodies, Nanobodies® show:
— high target specificity
— high affinity for their target
— low inherent toxicity.
However, like small molecule drugs they have the opportunity to inhibit enzymes and readily access receptor clefts. Furthermore, Nanobodies® in comparison to conventional antibodies:
— are extremely stable
— have the potential to be administered by means other than injection
— are easy to manufacture.
Ablynx’s Nanobodies® have a high homology with the VH domains of human antibodies and can be further humanised without loss of activity. Importantly, Nanobodies® have a low immunogenic potential, which has been confirmed in primate studies with Nanobody® lead compounds.
About Ablynx
Ablynx is a biopharmaceutical company engaged in the discovery and development of Nanobodies®, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious and life-threatening human diseases. The Company began operations in 2002 in Ghent, Belgium and currently employs over 100 employees.
Ablynx is developing a portfolio of Nanobody®-based therapeutic programmes in a number of major disease areas, including inflammation, thrombosis, oncology and Alzheimer’s disease. Already Ablynx has generated Nanobodies® against more than 100 different disease targets. The company and its collaborators have obtained positive in vivo efficacy data from animal studies in five major therapeutic programmes in four disease areas. Importantly, Ablynx has shown the absence of any detectable immunogenicity for its Nanobody® development candidates in advanced primate studies.
Ablynx has ongoing research collaborations and significant, multi-target partnerships with several major pharmaceutical companies, including Boehringer Ingelheim, Wyeth Pharmaceuticals, Novartis, Centocor (J&J), Kirin Brewery and P&G Pharma. Ablynx is building a diverse and broad portfolio of therapeutic Nanobodies® through these collaborations as well as through its own internal discovery programmes. Nanobody is a registered trademark of Ablynx NV.
SOURCE: Ablynx NV
