Nanobodies®, a novel class of therapeutic proteins based on single-domain antibody fragments, have been generated against more than 150 different disease targets. Efficacy data has been obtained in more than 26 in vivo models for Nanobodies against a range of different targets.

ALX-0061 is a Nanobody binding to the interleukin-6 receptor (IL6R). The involvement of the interleukin-6 (IL-6) pathway in a variety of diseases indicates that multiple indications can be pursued with large market potential including rheumatoid arthritis, Crohn’s disease, Castleman’s disease, multiple myeloma and systemic lupus erythematosus. Although there are biologics on the market for the treatment of rheumatoid arthritis, there is a clear unmet medical need for novel rheumatoid arthritis treatments because many patients are not sufficiently helped by current disease-modifying therapies, such as TNF-alpha therapies and methotrexate.

ALX-0061 has a very high potency and demonstrated a favourable PKPD and safety profile in preclinical testing compared with the benchmark molecule. ALX-0061 has no Fc-mediated effector function, which might translate into an improved safety profile. It also avoids cross-linking IL6R owing to its monovalent binding to the target.

The low molecular weight (26 kDa) and biophysical properties of this Nanobody open up opportunities for alternative routes of administration and superior tissue penetration in the clinical setting. The Nanobody can be manufactured at a relatively low cost in a microbial system.