Ablynx : 10/10/2016 ABLYNX INITIATES A PHASE III FOLLOW-UP STUDY OF ITS FIRST-IN-CLASS WHOLLY-OWNED ANTI-vWF NANOBODY, CAPLACIZUMAB, FOR THE TREATMENT OF ACQUIRED TTP

• To evaluate the long-term safety and efficacy of caplacizumab
• To evaluate the safety and efficacy of repeated treatment with caplacizumab
• To characterise the severity and long term impact of acquired TTP

Acquired TTP is an acute, ultra-rare, life-threatening blood clotting disorder in which uncontrolled platelet aggregation and microclot formation cause small blood vessel occlusions throughout the body1, resulting in thrombotic complications and widespread organ damage2. Despite the current standard-of-care treatment of daily plasma exchange (PEX) and immunosuppression, episodes of aTTP are still associated with a mortality rate of up to 20%, with most deaths occurring within 30 days of diagnosis3. Furthermore, patients are at risk of acute thromboembolic complications (e.g. stroke, venous thrombosis and myocardial infarction) and of recurrence of disease. In addition, some patients are refractory to therapy4, which is associated with a very poor prognosis for survival of an acute episode of aTTP. Long term, patients are at increased risk of hypertension, major depression, and premature death.

The objectives of this study are to evaluate the long-term safety and efficacy of caplacizumab and repeated use of caplacizumab, and to characterise the long term impact of aTTP. Patients will attend twice yearly visits and undergo a number of clinical, cognitive, and quality of life assessments. Safety laboratory parameters, immunogenicity of repeated treatment with caplacizumab and disease-related markers will be evaluated.

Upon any recurrence of acquired TTP, standard-of-care treatment consisting of daily plasma exchange (PEX) and immunosuppression will be initiated together with open-label caplacizumab. Patients will receive an intravenous bolus injection of caplacizumab at the start of PEX treatment followed by daily subcutaneous injections for the duration of daily PEX and for 30 days thereafter. Treatment with caplacizumab may be extended in the case of persistent signs and symptoms of underlying disease (e.g. ADAMTS13 activity profile remains below 10%).

The study duration is anticipated to be approximately three years from the date the last patient rolls over from the HERCULES trial.

1 Veyradier, NEJM 2016: "von Willebrand Factor - A new target for TTP treatment?"

2 Scully et al, Br J Hem 2012; Sarode et al, J Clin Apher 2014; Chaturvedi et al, Am J Hem 2013

3 Benhamou, Y. et al., Haematologica 2012

4 Defined as: 'failure of platelet response after 7 days despite daily plasma exchange treatment' or 'absence of platelet count doubling after 4 days of standard treatment, and LDH>upper limit of normal

invest in our own commercial infrastructure and key expertise to support the anticipated launch of caplacizumab in Europe and North-America."

Caplacizumab is a highly potent and selective bivalent anti-von Willebrand Factor (vWF) Nanobody® that received Orphan Drug Designation in the United States and Europe in 2009. Caplacizumab blocks the interaction of ultra-large vWF multimers (ULvWF) with platelets and, therefore, has an immediate effect on platelet aggregation and the ensuing formation and accumulation of the microclots that cause the severe thrombocytopenia and organ and tissue damage in aTTP. This immediate effect protects the patient from the manifestations of the disease while the underlying disease process resolves.

The efficacy and safety of caplacizumab in conjunction with the standard of care (PEX) were evaluated in the Phase II TITAN study in 75 patients with aTTP. Caplacizumab was well-tolerated and the primary endpoint of reduction in time to platelet normalisation was met (p=0.005). Treatment with caplacizumab resulted in a nearly 40% reduction in time to platelet count normalisation as compared to placebo (i.e., a faster reversion of thrombocytopenia with consequent reduced use of PEX). Moreover, during treatment, caplacizumab reduced aTTP recurrences by 71% compared to placebo when administered as an adjunct to standard of care5. Post-hoc analyses of the Phase II TITAN study data5 were performed to assess the impact of caplacizumab on a composite endpoint of major thromboembolic complications and aTTP-related mortality, as well as on refractoriness to standard treatment. The results demonstrate that a clinically meaningful lower proportion of subjects treated with caplacizumab experienced one or more major thromboembolic events, or died, as compared to placebo (11.4% versus 43.2%). In addition, fewer caplacizumab-treated patients, compared to those who received placebo, were refractory6 to treatment (5.7% versus 21.6%; and 0% versus 10.8%, respectively depending on the definition of refractoriness4). There were two deaths in the placebo group and both those patients were refractory to treatment; no deaths were reported in the caplacizumab group.

These Phase II results will serve as the basis for filing for conditional approval of caplacizumab in Europe in early 2017. The confirmatory Phase III HERCULES study is currently ongoing and will support the BLA filing in the United States. Results from this Phase III study are expected by the end of 2017.

Caplacizumab has the potential to be the first therapeutic specifically approved for the treatment of acquired TTP.

aTTP is an acute, ultra-rare, life-threatening, blood clotting disorder, affecting up to 11 per million people worldwide. It has a sudden onset caused by impaired activity of the ADAMTS13 enzyme (typically 1, leading to thrombotic complications and widespread organ damage2.

Up to 20% of patients die from an initial aTTP episode with most deaths occurring within 30 days of diagnosis3. In addition to the acute risks of the disease, patients experiencing an episode of aTTP may suffer long-term consequences such as cognitive deficits, depression, and arterial hypertension7, and are at risk for recurrence. The recurrence rate ranges from 10-84%8 and typically occur within 1-2 years9, but recurrences have been reported up to 30 years after the initial episode10.

5 Press release June 2014; Manuscript in the NEJM, Feb 2016; presentation at EHA 2016; presentation at ECTH 2016

6 Peyvandi et al, notes to editor NEJM 2016

7 Deford et al, Blood 2013

8 Thejeel et al, American journal of hematology 2016

9 Kremer Hovinga et al, Blood 2010

10 Falter et al, Hamostaseologie 2013

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 45 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 KGaA, Novartis, Novo Nordisk and Taisho Pharmaceuticals. The Company is headquartered in Ghent, Belgium. More information can be found on www.ablynx.com.

Julia Phillips, Brett Pollard, Mo Noonan, Matthew Moss t: +44 20 3727 1000

e: ablynx@fticonsulting.com

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors' current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its parent or subsidiary undertakings or any such person's officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.