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Ablynx Initiates a Multinational Phase III Study with Caplacizumab in Patients with Acquired TTP, a Rare Blood Clotting Disorder

Ablynx Initiates a Multinational Phase III Study with Caplacizumab in Patients with Acquired TTP, a Rare Blood Clotting Disorder

  • Caplacizumab is a first-in-class anti-von Willebrand factor (vWF) Nanobody® in development for the treatment of acquired thrombotic thrombocytopenic purpura (TTP)
  • Acquired TTP is an acute, potentially life-threatening ultra-rare blood clotting disorder with a high unmet medical need, that affects about 11 per million people worldwide
  • Caplacizumab demonstrated promising clinical efficacy  in patients with acquired TTP in the Phase II TITAN study 
  • Ablynx is on track to file for conditional approval of caplacizumab in Europe in 2017 for the treatment of acquired TTP

GHENT, Belgium - 29 September 2015 - Ablynx [Euronext Brussels: ABLX; OTC: ABYLY] today announced the initiation of a multinational, double-blind placebo-controlled Phase III “HERCULES” study evaluating efficacy and safety of caplacizumab, its wholly-owned anti-vWF Nanobody, in acquired TTP.  The study is expected to enrol 92 patients at clinical sites across 17 countries.

Acquired TTP is an ultra-rare acute blood clotting disorder that leads to the formation of microvascular thrombosis (blood clots in small blood vessels) and organ damage throughout the body, including the brain and the heart. Mortality remains high at 10-20% and about 36% of patients suffer from relapses after initial treatment even with the current standard-of-care, which consists of plasma exchange (PE) plus immune-suppressive treatment. In addition, the organ damage caused by a TTP episode may result in poor longer term outcomes.

There remains a high unmet medical need to immediately inhibit the formation of microvascular thrombi, thereby reducing the risk of further organ damage. Maintenance of this platelet-protective effect is required until the underlying auto-immune activity has been resolved. Caplacizumab is being developed to address this unmet need and its clinical effect has been demonstrated in the Phase II TITAN study.

The Phase III “HERCULES” study will evaluate the efficacy and safety of caplacizumab in patients with acquired TTP when administered in addition to the standard-of-care. The primary endpoint is time to platelet count normalisation, a measure of prevention of further microvascular thrombosis. Other clinically relevant endpoints include the prevention of recurrence of the presenting TTP episode after stopping daily PE, the effect on biomarkers of organ damage, severe morbidity associated with ischemia, and the mortality rate.

Dr Edwin Moses, CEO of Ablynx commented:
“The ability of caplacizumab to rapidly inhibit the formation of small blood clots, resulting in the more rapid restoration of normal platelet counts and an important reduction in exacerbations, was well demonstrated in the Phase II TITAN study. Based on the clinical effect seen in this TITAN study, we are planning to submit caplacizumab for conditional approval to the European Medicines Agency (EMA) in 2017. We now look forward to enrolling 92 patients into our Phase III “HERCULES” study which we plan to have completed by the end of 2017 to support a BLA filing in the United States in 2018. In parallel with the clinical development and regulatory preparations, we are committed to preparing to lead the commercialisation of caplacizumab in Europe and the United States to make this product available for patients suffering from this potentially life-threatening disorder”.

About thrombotic thrombocytopenic purpura (TTP)
TTP exists in two forms: a congenital and an acquired form, with the latter accounting for >90% of the patients. The condition is characterised by severe thrombocytopenia (low blood platelet count), haemolytic anaemia (abnormal break down of red blood cells) and signs and symptoms of tissue ischemia (insufficient blood supply to organs) including stroke or myocardial infarctions. The ischemic damage may result in both acute complications as well as poor longer term outcomes. In the majority of patients, it is an autoimmune condition where auto-antibodies are generated to the enzyme ADAMTS13, which is responsible for ultra large vWF (ULvWF) cleavage. As a result of impaired ADAMTS13 activity (typically <10% that in normal plasma), these ULvWF molecules spontaneously bind to platelets, resulting in ULvWF mediated platelet string formation in the small blood vessels.

About caplacizumab
Caplacizumab is a highly potent and selective bivalent anti-vWF Nanobody that received Orphan Drug Designation in the US and EU in 2009. It could be the first drug specifically approved for the treatment of acquired TTP.

Caplacizumab inhibits the interaction between vWF and platelets by targeting the A1 domain of vWF and thus has the potential to immediately block the ULvWF mediated platelet interactions and the formation of the string-like clots in the blood of patients with acquired TTP.

About Ablynx
Ablynx is a biopharmaceutical company engaged in the development of Nanobodies®, proprietary therapeutic proteins based on single-domain antibody fragments, which combine the advantages of conventional antibody drugs with some of the features of small-molecule drugs. Ablynx is dedicated to creating new medicines which will make a real difference to society. Today, the Company has more than 30 proprietary and partnered programmes in development in various therapeutic areas including inflammation, haematology, immuno-oncology, oncology and respiratory disease. The Company has collaborations with multiple pharmaceutical companies including AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck & Co., Inc., Merck Serono, Novartis and Taisho Pharmaceutical Co., Ltd. The Company is headquartered in Ghent, Belgium. More information can be found on

Issued for and on behalf of Ablynx by Instinctif Partners.
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Sue CharlesManaging Partner