Ablynx, a biotechnology company based in Ghent, Belgium, emerged in 2001 as a spin-off from the Vlaams Instituut voor Biotechnologie (VIB) and the Free University of Brussels (VUB). The company aimed to pioneer novel biological treatments for various diseases, leveraging a scientific discovery with the potential to transform therapy development.
Understanding Nanobodies
Nanobodies are unique antibody fragments, significantly smaller than conventional antibodies. Derived from heavy-chain-only antibodies found in camelids like camels, llamas, and alpacas, they possess only heavy chains. Their variable domain is capable of binding to antigens. These single-domain antibody fragments, also known as VHHs, typically weigh between 12 and 15 kilodaltons (kDa), about one-tenth the size of a conventional 150 kDa antibody.
Their small size provides several advantages, including enhanced tissue penetration, reaching targets larger antibodies might not. Nanobodies also exhibit high stability across a wide range of temperatures and pH levels, and are highly soluble. This robust nature makes them easier to produce and modify. Their unique structure, featuring an extended complementarity-determining region 3 (CDR3) loop, enables binding to recessed or “hidden” sites on antigens often inaccessible to larger antibodies.
Therapeutic Applications of Nanobodies
Nanobodies are promising candidates for treating various medical conditions. Their small size and tissue penetration allow targeting antigens in weakly vascularized or poorly accessible areas, such as solid tumors. They are explored for inflammatory conditions like rheumatoid arthritis by blocking inflammatory pathways. Nanobodies also show promise in oncology, engineered to deliver cytotoxic compounds directly to cancer cells or activate immune responses against tumors.
Caplacizumab (Cablivi) is the first nanobody-based drug approved by regulatory bodies. Approved in Europe in 2018 and the United States in 2019, it treats adults experiencing acquired thrombotic thrombocytopenic purpura (aTTP). This rare, life-threatening blood disorder involves excessive clotting due to an ADAMTS13 enzyme deficiency. Caplacizumab works by binding to the A1 domain of von Willebrand factor (vWF), inhibiting platelet aggregation and reducing dangerous micro-clots. Administered with plasma exchange and immunosuppressive therapy, it helps normalize platelet counts and reduce aTTP-related death or recurrence.
Ablynx’s Journey and Legacy
Ablynx’s innovative work culminated in its acquisition by Sanofi in January 2018 for approximately €3.9 billion ($4.8 billion). This acquisition followed an earlier rejected offer from Novo Nordisk. The unanimous approval by both boards underscored their strategic alignment.
The acquisition allowed Sanofi to integrate Ablynx’s nanobody technology platform, including a pipeline of over 45 drug candidates. Sanofi committed to maintaining Ablynx’s scientific center in Ghent, Belgium, signaling continued nanobody research and development. This expanded Sanofi’s late-stage pipeline and reinforced its focus on rare blood disorders, leveraging advancements like Caplacizumab. Sanofi continues to apply nanobody technology in drug discovery, particularly within hematology, inflammation, and immuno-oncology.