The power of Ablynx's discovery platform has resulted in a Nanobody® development candidate. Ablynx’s lead programme,
ALX-0081, became the first ever single domain antibody to enter clinical trials and Ablynx reported the final positive results from its Phase I study in December 2007. Following these positive results, Ablynx has initiated a Phase Ib multiple-dose study in May 2008, directly in the target patient population rather than healthy volunteers for ALX-0081.
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®:are extremely stable, have the potential to be administered by means other than injection and are easy to manufacture.
Ablynx’s Nanobodies® have a high homology with the VH domains of human antibodies and can be further humanised without any loss of activity. Importantly, Nanobodies® have a low immunogenic potential, which has been confirmed in primate studies with Nanobody® lead compounds.