Exhibit 99.1

Annual Report 2016

uniQure N.V.

Amsterdam, April 14, 2017

Table of Contents

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A                                       Report of the Board of Directors

1                                         Introduction

a)                                     Forward-looking statements

This Annual Report and the Consolidated Financial Statements contain “forward-looking statements” as defined under U.S. federal securities laws. Many of these statements can be identified by the use of terminology such as “believes,” “expects,” “anticipates,” “plans,” “may,” “will,” “projects,” “continues,” “estimates,” “potential,” “opportunity” and similar expressions.

Our actual results or experience could differ significantly from the forward-looking statements. These statements are subject to various risks, uncertainties and assumptions. Our actual results of operations may differ materially from those stated in or implied by such forward-looking statements as a result of a variety of factors, including those described under “Risk Factors” and elsewhere in this Annual Report and in our Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission. You should carefully consider that information before you make an investment decision.

You should not place undue reliance on these statements, which speak only as of the date that they were made. These cautionary statements should be considered in connection with any written or oral forward-looking statements that we may make in the future. We do not undertake any obligation to release publicly any revisions to these forward-looking statements after completion of the Annual Report to reflect later events or circumstances or to reflect the occurrence of unanticipated events. All forward-looking statements attributable to us are expressly qualified in their entirety by these cautionary statements.

In addition, with respect to all of our forward-looking statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

b)                                     History and development of uniQure

uniQure N.V. (“uniQure” or the “Company”) is a biopharmaceutical company which was founded in 1998 by scientists who were investigating Lipoprotein Lipase Deficiency (“LPLD”) at the Academic Medical Center of the University of Amsterdam. The Company initially operated through its predecessor company, Amsterdam Molecular Therapeutics Holding N.V. (“AMT”). The Company was incorporated in January 2012 to acquire and continue the gene therapy business of AMT which is domiciled in the Netherlands. Effective February 10, 2014, in connection with its initial public offering, the Company converted into a public company with limited liability and changed its legal name from uniQure B.V. to uniQure N.V. The Company is registered with the Dutch Trade Register of the Chamber of Commerce (handelsregister van de Kamer van Koophandel en Fabrieken) in Amsterdam, the Netherlands under number 54385229. The Company’s headquarters is in Amsterdam, the Netherlands, and its registered office is located at Meibergdreef 61, Amsterdam 1105 BA, the Netherlands, and its telephone number is +31 20 240 6000.

uniQure is registered with the Dutch Trade Register of the Chamber of Commerce (handelsregister van de Kamer van Koophandel en Fabrieken) in Amsterdam, the Netherlands under number 54385229. Our corporate seat is in Amsterdam, the Netherlands, and our registered office is located at Meibergdreef 61, Amsterdam 1105 BA, the Netherlands, and our telephone number is +31 20 240 6000. Our website address is www.uniqure.com. Our ordinary shares are traded on the NASDAQ Global Select Market under the symbol “QURE”.

c)                                      Business overview

We are a leader in the field of gene therapy, seeking to develop single treatments with potentially curative results for patients suffering from genetic and other devastating diseases. We are advancing a focused pipeline of innovative gene therapies that have been developed both internally and through partnerships, such as our collaboration with Bristol Myers-Squibb focused on cardiovascular diseases. We have established clinical proof-of-concept in our lead indication hemophilia B and achieved preclinical proof-of-concept in Huntington’s disease. We believe our validated technology platform and manufacturing capabilities provide us distinct competitive advantages, including the potential to reduce development risk, cost and time to market. We produce our AAV-based gene therapies in our own facilities with a proprietary, commercial-scale, consistent, manufacturing process. We believe our Lexington, Massachusetts-based facility is one of the world’s leading, most versatile, gene therapy manufacturing facilities.

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In November 2016, we announced the completion of our strategic review process aimed at refocusing our pipeline, reducing operating costs and delivering long-term shareholder value. The strategic restructuring plan includes the following key elements:

·                  Prioritizing the development of our product candidates in hemophilia B and Huntington’s disease, as well as those programs associated with our collaboration with Bristol-Myers Squibb in cardiovascular disease. We intend to initiate late stage development of our product candidate for hemophilia B, pending discussions with regulatory authorities and to file investigational new drug (“IND”) applications for Huntington’s disease and S100A1 following the completion of ongoing IND-enabling studies.

·                  Deprioritizing investments in our gene therapy programs targeting Sanfilippo B and Parkinson’s disease and initiating discussions with collaborators regarding potential options, including the transition or partnering of these programs.

·                  Leveraging our manufacturing capabilities and next-generation vector and promoter platform to generate new best-in-class products, with an emphasis on rare and orphan diseases.

·                  Consolidating our manufacturing activities at our Lexington, MA facility.

·                  Maintaining a smaller, but fully integrated research and development organization in Amsterdam, the Netherlands.

·                  Eliminating the previous organizational structure based on therapeutic areas of focus and realigning the organization around core program teams.

Update on research and development activities during 2016

A summary of our key development targets as of December 31, 2016, is provided below:

AMT-060 for Hemophilia B

Hemophilia B Disease and Market Background

Hemophilia B is a serious and rare inherited disease in males characterized by insufficient blood clotting. The condition can lead to repeated and sometimes life-threatening episodes of external and internal bleeding following accidental trauma or medical interventions. Severe hemophilia is characterized by recurrent episodes of spontaneous joint bleeds that cause long-term damage to the joints resulting in disabling arthropathy. Bleeds may be fatal if they occur in the brain. The deficient blood clotting results from the lack of functional human Factor IX (“hFIX”). Treatment of hemophilia B today consists of prophylactic or on-demand protein replacement therapy, in which one to three times weekly intravenous administrations of plasma-derived or recombinant hFIX are required to prevent bleeding and once daily infusions in case bleeding occurs. Hemophilia B occurs in approximately 1 out of 30,000 live male births.

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Our Development of AMT-060

We are developing AMT-060, a gene therapy for the treatment of hemophilia B. We are targeting

·                  long-term safety,

·                  sustained, therapeutically relevant increases in FIX activity levels, and

·                  a reduction in both consumption of FIX replacement therapy and bleeding rates.

We are enrolling male patients from multiple countries with either severe (<1%) or moderately severe (<2%) hemophilia B on prophylactic (precautionary) or on-demand FIX replacement therapy, but in either case with a severe bleeding phenotype. We have entered into a co-development agreement with Chiesi Farmaceutici S.p.A. (“Chiesi”) for the development and commercialization of AMT-060 in the European Union and other specified countries.

AMT-060 consists of the AAV5 vector carrying a human Factor IX (“FIX”) gene cassette that we have exclusively licensed from St. Jude. We produce this vector with our insect cell-based manufacturing process. We are designing this therapy for systemic administration through intravenous infusion in a single treatment. We are observing a therapeutic benefit from AMT-060 that is superior to patients’ previous prophylactic FIX replacement therapy regimen, even in patients with advanced joint disease who still experienced many bleeds despite prophylaxis with FIX.

Phase I/II Clinical Trial

In the third quarter of 2015, we initiated our Phase I/II clinical trial of AMT-060 in patients with severe or moderately-severe hemophilia B.

The study is a 5-year, open-label, uncontrolled, single-dose, dose-ascending multi-center trial that includes two cohorts, with the low-dose cohort using a treatment of 5x1012 gc/kg and the second-dose cohort using 2x1013 gc/kg. It is administered, without immunosuppressant therapy, through the peripheral vein in a single treatment session for approximately 30 minutes. All patients are screened for pre-existing anti-AAV5 antibodies before treatment, and Data Monitoring Committee reviews are conducted after each of the first two patients in each cohort as well as prior to dosing in the second cohort.

We enrolled a total of five patients into the low dose cohort in the third quarter 2015. Another five patients were enrolled into the high dose cohort between March and May 2016.

We presented the most recent data from the study on December 5, 2016, at the 58th annual meeting of the American Society of Hematology (“ASH”).

Data from the second-dose cohort showed a dose response with improvement in disease state in all five patients, including the discontinuation of prophylactic FIX infusions in all four patients that previously required chronic replacement therapy. As of the data cutoff date for the ASH presentation, only one unconfirmed spontaneous bleed was reported during an aggregate of 94 weeks follow-up after discontinuation of prophylactic FIX replacement therapy, representing a reduction in the annualized spontaneous bleed rate of 76% compared to the one-year period prior to administration of AMT-060. Through up to 6 months of follow-up among the five patients in the second-dose cohort, the mean steady-state FIX activity was approximately 7% of normal, with expression up to a FIX activity of 13% of normal.

All five patients in the low-dose cohort, whose bleedings were previously uncontrolled despite being managed with prophylactic therapy, continue to maintain constant and clinically meaningful levels of FIX activity for up to 52 weeks post treatment, resulting in a complete cessation of spontaneous bleedings in the last 14 weeks of observation. Among the four patients that discontinued prophylactic FIX infusions, the annualized spontaneous bleed rate was reduced by 59% compared to the one year period prior to administration of AMT-060. Additionally, the annualized consumption of FIX concentrate following AMT-060 administration was reduced by more than a cumulative total of 1,329,000 international units (85%) compared to their pre-trial usage levels. The one patient who remained on prophylactic FIX therapy in the low-dose cohort experienced a 45% reduction in spontaneous bleeds and also requires materially less FIX concentrate after treatment with AMT-060.

AMT-060 continues to be well-tolerated, and there have been no severe adverse events. Three out of the total of 10 patients (two in the second-dose cohort and one previously reported from the low-dose cohort) experienced mild, asymptomatic elevations of alanine aminotransferase (“ALT”) and received a tapering course of corticosteroids per protocol. Importantly, the temporary elevations in ALT were not associated with any loss of endogenous FIX activity or T-cell response to the AAV5 capsid.

No patients across either cohort have developed inhibitory antibodies against FIX and no patients screened in the study tested positive for anti-AAV5 antibodies.

On January 30, 2017, we received a Breakthrough Therapy designation by the FDA for our AMT-060 program. This designation is based on results from the ongoing Phase I/II clinical trial.

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Huntington’s Disease

Huntington’s disease (“HD”) is a severe genetic neurodegenerative disorder causing loss of muscle coordination, behavioral abnormalities and cognitive decline, resulting in complete physical and mental deterioration over a 12 to 15 year period. The median survival time after onset is 15 to 18 years (range: 5 to >25 years). Causes of death include pneumonia (~33%), other infections, heart disease (~25%), suicide (~7%), choking, physical injury (e.g., falls), and malnutrition. HD is caused by an inherited defect in a single gene that codes for protein called Huntingtin (“HTT”). The prevalence of HD is 2.71 per 100,000 in the general population, similar in men and women, and it is therefore considered as rare disease. Despite the ability to identify HD mutation carriers decades before onset, there is currently no available therapy that can delay onset or slow progression of the disease. Although some symptomatic treatments are available, they only are transiently effective despite significant side effects.

Our product candidate AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA which silences the Huntingtin gene. The therapeutic goal is to inhibit the production of the mutant protein. Findings published the peer-reviewed journal Molecular Therapy-Nucleic Acids provide preclinical proof of concept for AMT-130 and demonstrate the potential of a one-time administration of AAV5-delivered gene therapy into the CNS to silence HTT. The paper, titled “Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington’s Disease” describes multiple approaches to silencing HTT using expression cassette-optimized artificial microRNAs (“miHTTs”).

Several miHTT scaffolds were incorporated in an AAV5 vector using our established baculovirus-based manufacturing platform and administered to a humanized mouse model. The data demonstrate strong silencing of mutant HTT and total HTT silencing in vitro and in vivo. Furthermore, it was shown that HTT knock-down efficiency could be increased to 80% by using optimized miHTT scaffolds. These efficient knock down data were also observed in a larger animal species, mini pigs, a model that is explored as a large animal model for HD.

In parallel, studies for HTT silencing and bio distribution were initiated in non-human primates during 2016. The results of both large animal studies will be used to design the safety program of AMT-130 to support the filing of an investigative new drug application with the FDA.

S100A1 for Congestive heart failure

Collaboration with Bristol-Myers Squibb (“BMS”)

In April 2015, we entered into an agreement with BMS that provides exclusive access to our gene therapy technology platform for multiple targets in cardiovascular (and other) diseases (“Collaboration and License Agreement”). The collaboration included our proprietary gene therapy program for congestive heart failure which aims to restore the heart’s ability to synthesize S100A1, a calcium sensor and master regulator of heart function, and thereby improve clinical outcomes for patients with reduced ejection fraction. Beyond cardiovascular diseases, the agreement also included the potential for a target exclusive collaboration in other disease areas. In total, the companies may collaborate on ten targets, including S100A1.

We are leading the discovery, non-clinical, analytical and process development effort and are responsible for manufacturing of clinical and commercial supplies using our vector technologies and industrial, proprietary insect-cell based manufacturing platform, while BMS leads development and regulatory activities across all programs and is responsible for all research and development costs. BMS will be solely responsible for commercialization of all products from the collaboration.

In July 2015, three additional targets for development in cardiovascular indications were agreed with BMS. The development process for two of these new targets commenced in 2016 with producing initial material for research and development.

Congestive heart failure is the inability of the heart to supply sufficient blood flow to meet bodily demand for oxygen and nutrition. CHF is a rapidly progressing disease affecting 26 million people worldwide, with patients suffering from severe heart failure facing a 5-year mortality rate of over 50%. According to the American Heart Association, the prevalence of CHF is expected to double or triple by 2030. Maladaptive changes in the molecular composition of the diseased heart muscle contribute to its loss of contractile function, lethal tachyarrhythmia, energetic deficit, and maladaptive growth. Currently, there is no effective long-term or causative treatment for this disease.

S100A1 is intended to fill this therapeutic gap by improving cardiac function and targets a novel molecular regulatory mechanism that differs from previous therapeutic attempts to enhance cardiac muscle function, such as beta-AR agonists (e.g., dobutamine) or calcium sensitizers. S100A1 neither utilizes, nor relies on, components of the ß-adrenergic system to improve cardiac performance and conveys a cAMP-independent heightened systolic and diastolic contractile state. As such, S100A1 is intended to be fully compatible with current HF treatments due to its novel and independent mode of action. S100A1’s upstream position as a “master regulator” of a Ca2+-driven network in cardiomyocytes integrating contractility, metabolism, rhythm stability and growth, makes S100A1 a unique therapeutic target among other regulatory proteins in the heart.

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S100A1 protein is downregulated in human CHF molecular analysis characterized the S100A1 protein as an upstream “master” regulator of the cardiomyocyte-calcium driven network. S100A1 deficient hearts show accelerated progression to severe heart failure and increase mortality after cardiac damage. Elevated cardiomyocyte S100A1 protein levels are protective and prolong survival in mouse CHF models.

In 2015, we agreed with BMS to perform non-clinical studies that are expected to support an IND filing. Based on this plan, several non-clinical studies were performed in 2016:

·                  Pharmacokinetic and bio distribution studies utilizing the same baculovirus-derived material that will be used in the clinical trials; and

·                  Exploratory studies to assess the need for anterograde occlusion as part of the investigational product delivery method and assess the impact of neutralizing antibodies (“NAbs”) on therapeutic activity of S100A1.

The non-clinical studies target to obtain safety and efficacy data required for filing of an investigative new drug application with the FDA.

Glybera for LPLD

In October 2012, the European Commission granted marketing authorization for Glybera® under exceptional circumstances as a treatment for adult patients diagnosed with familial lipoprotein lipase deficiency (“LPLD”) confirmed by genetic testing, and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions.

Glybera is a gene therapy that is designed to restore the LPL enzyme activity required to enable the processing, or clearance, of fat-carrying chylomicron particles formed in the intestine after a fat-containing meal. The product consists of an engineered copy of the human LPL gene packaged with a tissue-specific promoter in a non-replicating AAV1 vector, which has a particular affinity for muscle cells. In order to improve activity, we use a naturally occurring variant of the LPL gene that has higher enzyme activity than the normal version of the gene that encodes the protein. We produce Glybera using our insect cell-based manufacturing process. Clinicians administer Glybera in a one-time series of up to 60 intramuscular injections in the legs. The patient is administered spinal anesthesia or deep sedation during the procedure. In addition, an immunosuppressive regimen is recommended from three days prior to and for 12 weeks following Glybera administration.

In the European Union, we have been granted orphan drug exclusivity for Glybera for treatment of LPLD until October 2022. The first commercial patient in Europe was treated with Glybera in September 2015.

The FDA has also granted orphan drug designation to Glybera for the treatment of LPLD. In November 2015, we announced that we are no longer pursuing the approval of Glybera in the U.S.

To fulfill the key conditions of the approval of Glybera by the EMA, we were required to implement a patient registry prior to commercial launch and to conduct post-approval clinical trials of Glybera. The patient registry was put in place in May 2014. In 2015, we completed a non-interventional healthy volunteer study to establish post-prandial chylomicron clearance test curves in 8 normal individuals following fat-containing standardized meal.

We currently plan to enroll 12 patients with LPLD into a phase IV study. We anticipate that the trial will be conducted as a multicenter trial including sites in the United States and Canada. The EMA has approved an initial protocol for this clinical trial in 12 patients. We also developed an improved manufacturing process for Glybera, which addresses our post-approval commitments and received EMA approval in January 2016.

Other Early-Stage Research

We are pursuing the research of several other gene therapy candidates targeting rare and orphan diseases. Our focus is on genetic diseases affecting the liver, including hemophilia A, as well as various CNS disorders.

Vector Development

We are seeking to develop next-generation vectors with increased potency to target liver indications in which high relative percentage increases in the secretion of a protein above the disease state would be required for therapeutic benefit. One approach we are using is directed evolution, which involves a vector selection process in which libraries of mutant variants are screened for optimal properties. These next-generation vectors may be used in the development of a gene therapy for hemophilia A as well as other therapeutic indications. In January 2014, we entered into a collaboration and license agreement with 4D for the discovery and optimization of next-generation AAV vectors targeting the liver and the brain.

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Collaborations

Bristol-Myers Squibb Collaboration

In April 2015, we entered into a series of agreements with BMS, a publicly traded pharmaceutical company, regarding a collaboration that provides BMS with exclusive access to our gene therapy technology platform for multiple targets in cardiovascular and potentially other diseases.

Collaboration and License Agreement

With respect to the Collaboration and License Agreement with BMS, we refer to the section above.

We have received a total of $140.0 million to date from BMS, including an upfront payment of $50.0 million at the closing of the collaboration, which occurred in May 2015, a $15.0 million payment for the selection of three collaboration targets, in addition to S100A1, and approximately $75.5 million in two equity investments. We will be eligible to receive additional payments for further designation of new collaboration targets and upon the achievement of research, development and regulatory milestones, including up to $254.0 million for the lead S100A1 therapeutic and up to $217.0 million for each other gene therapy product developed under the collaboration. We will also be eligible to receive net-sales-based milestone payments and tiered single to double-digit royalty payments on product sales.

Equity Agreements

In June 2015, BMS acquired 1.1 million ordinary shares, or 4.9% of our outstanding ordinary shares following the issuance, at a purchase price of $33.84 per share for aggregate consideration of $37.6 million. In August 2015, BMS acquired an additional 1.3 million ordinary shares at a purchase price of $29.67 per share for aggregate consideration of $37.9 million. Immediately after the second equity investment, BMS held 9.9% of our outstanding ordinary shares.

We have also granted BMS two warrants. Pursuant to each agreement, BMS may at its option acquire an additional number of shares equal to up to 5.0% of our outstanding ordinary shares (10.0% in the aggregate) immediately after each such issuance at a premium to the market. The exercise of each warrant is conditioned upon the designation of a specified number of additional collaboration targets and payment of related fees by BMS, as well as a minimum number of collaboration programs under development.

The total number of ordinary shares that may be acquired by BMS pursuant to these agreements is equal to 19.9% of the total number of ordinary shares outstanding following such issuances.

We also entered into an Investor Agreement with BMS regarding the rights and restrictions relating to the ordinary shares to be acquired by BMS. We have granted BMS certain registration rights that allow BMS to require us to register our securities beneficially held by BMS under the Exchange Act. BMS may make up to two such demands (or three, in the event that either warrant is exercised) for us to register the shares, provided that we may deny such demand if (i) the market value of the shares to be registered is less than $10 million (provided however, if BMS holds less than $10 million worth of our shares, we must comply with their demand for registration), (ii) we certify to BMS that we plan to effect a registration within 120 days of their demand or we are engaged in a transaction that would be required to be disclosed in a registration statement and that is not reasonably practicable to be disclosed at that time, or (iii) we have already effected one registration statement within the twelve months preceding BMS’s demand for registration. In addition, upon the occurrence of certain events, we must also provide BMS the opportunity to include the shares they hold in any registration statement that we effect independent of any demand registration.

We have also granted BMS certain information rights under the Investor Agreement, although these requirements may be satisfied by our public filings required by U.S. securities laws.

Pursuant to the Investor Agreement, without our consent, BMS may not (i) acquire a number of shares such that the number of shares that BMS beneficially holds is greater than the percentage acquired, or which may be acquired, after giving effect to each of the tranches under the Share Subscription Agreement and the two warrants; (ii) propose, offer or participate in any effort to acquire us or one of our subsidiaries; (iii) propose, offer or participate in a tender offer for our shares or any exchange of shares that would effect a change of control of our company; (iv) seek to control or influence our governance or policies; (v) join or participate in any group regarding the voting of our ordinary shares; or (vi) take certain other similar actions. BMS may still, among other things, make a non-public, confidential proposal to enter into a business combination or similar transaction with our company. These stand still restrictions will terminate upon the occurrence of certain events including, but not limited to, the acquisition of a certain material number of shares by a third party, if we enter into a merger agreement or similar transaction with a third party, or upon the passage of a defined period of time subsequent to the acquisition of shares pursuant to the Share Subscription Agreement or the warrants.

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BMS is also subject to a lock-up pursuant to the Investor Agreement. Without our prior consent, BMS may not sell or dispose of its shares until the later of (i) the fourth anniversary of the purchase of the first tranche of shares pursuant to the Share Subscription Agreement (or fifth anniversary if the Collaboration Agreement is extended), or (ii), in respect of each ordinary share acquired pursuant to the Share Subscription Agreement and the warrants, the first anniversary of issuance of each such ordinary shares. However, this lock-up may terminate sooner in the event the Collaboration Agreement is terminated.

The Investor Agreement also requires BMS to vote all of our ordinary shares it beneficially holds in favor of all items on the agenda for the relevant general meeting of shareholders of our company as proposed on behalf of our company, unless, in the context of a change of control or similar transaction, BMS has itself made an offer to our company or our supervisory or management boards in connection with the transaction that is the subject of the vote, in which case it is free to vote its shares at its discretion. This voting provision will terminate upon the later of the date on which BMS no longer beneficially owns at least 4.9% of our outstanding ordinary shares, the closing of a transaction that provides BMS exclusive and absolute discretion to vote our shares it beneficially holds, or the termination of the Collaboration Agreement for breach by us.

Chiesi Hemophilia B Commercialization and Development Agreement

We have entered into an agreement with Chiesi, a family-owned Italian pharmaceutical company, for the co-development and commercialization of our hemophilia B program. We have retained full rights in the United States, Canada and Japan under this agreement. We received a €17.0 million upfront payment under this agreement, as well as a €14.0 million investment in our ordinary shares, both in July 2013. This agreement provides us with research funding for further development of our hemophilia B product candidate, and further provides that we will also receive payments from Chiesi for any commercial quantities of our hemophilia B product candidate we manufacture and supply to them, if we receive regulatory approval for such product candidate. We estimate that the amount we would retain, net of cost of goods sold, including third party royalties and related amounts, will be between 25% and 35% of the revenues from sales of such product by Chiesi, varying by country of sale.

Chiesi Glybera Commercialization

We will receive payments from Chiesi for the quantities of Glybera we manufacture and supply to them. Based on our estimates, we anticipate we will retain in the range of 20% to 30% of the net sales of Glybera by Chiesi in the European Union and other countries under our agreement, net of the cost of goods sold, including the royalties and other obligations we owe to third parties. In addition, we are required to repay 20% of the gross amount received from Chiesi related to Glybera sales in repayment of a technical development loan from the Dutch government.

Early-Stage Collaborations

4D Molecular Therapeutics

In January 2014, we entered into a collaboration and license agreement with 4D for the discovery and optimization of next-generation AAV vectors. Under this agreement, 4D has granted us an exclusive, worldwide license, with the right to grant sublicenses, to 4D’s existing and certain future know-how and other intellectual property, including certain patent rights 4D has exclusively licensed from the Regents of the University of California, to develop, make, use and sell certain AAV vectors and products containing such AAV vectors and gene constructs, for delivery of such gene constructs to CNS or liver cells for the diagnosis, treatment, palliation or prevention of any disease or medical condition. Under this collaboration, the 4D team, including Dr. David Schaffer, 4D’s co-founder and Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley, has established a laboratory to identify next generation AAV vectors. In addition, in connection with our entry into this collaboration, Dr. Schaffer became a member of our Board.

We funded a three-year (2014-2016) research collaboration, which has been extended for an additional year, under a mutually agreed research plan. We are entitled to select a specified number of AAV variants from the research collaboration. We have exclusive rights to further research, develop, manufacture and commercialize the selected AAV variants, as well as AAV vectors and products containing such AAV variant and gene constructs, or licensed products. During the research collaboration and throughout the term of the agreement, 4D has agreed to work exclusively with us to research, develop, manufacture and commercialize AAV variants, AAV vectors and products containing AAV vectors and gene constructs, for delivery of gene constructs to CNS or liver cells for the diagnosis, treatment, palliation or prevention of any disease or medical condition.

Our research collaboration with 4D is guided by a joint research steering committee. Our payment obligations under the agreement include the research collaboration funding described above as well as payments for the achievement of specified preclinical, clinical and regulatory milestones of up to $5,000,000 for each licensed product that we develop under the collaboration. We have also agreed to pay 4D royalties equal to a single-digit percentage of net sales, if any, of licensed products by us or our affiliates. We also pay 4D a low to upper-low double-digit percentage of any sublicensing income we receive, subject to a floor of a low single-digit percentage of net sales, if any, by sublicensees of certain licensed products.

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Synpromics

In January 2015, we entered into an agreement with Synpromics, a UK-based biotechnology company, pursuant to which we intend to jointly fund research relating to the development of optimized viral promoters. Under the agreement, we have agreed to fund a specific testing program on liver promoters, with payments based on the achievement of specified milestones. Following the conclusion of the non-clinical testing phase, further milestones and payments have been agreed through the clinical phase of development and commercialization of products consisting of promoters developed under this agreement.

The research is directed at the discovery of alternative small liver-specific promoters for sustainable and increased expression of larger therapeutic genes fitting the package capacity of AAV vectors. Under the agreement, we will exclusively own the foreground IP that will be obtained following the assembly of synthetic promoters conceived under Synpromic’s patent-protected technology and have the sole right to pursue uniQure patent rights that cover the synthetic promoters. All rights are limited to AAV gene therapy in the liver field. We will on request grant Synpromics an exclusive, sublicensable license to the IP outside this field

Intellectual Property

Introduction

We strive to protect the proprietary technologies that we believe are important to our business, including seeking and maintaining patent protection in the United States, Europe and other countries for novel components of gene therapies, the chemistries and processes for manufacturing these gene therapies, the use of these components in gene therapies and other inventions and related technology that are important to our business, such as those relating to our technology platform. We also rely on trade secrets and careful monitoring of our proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business, defend and enforce our patents, maintain our licenses to use intellectual property owned by third parties, preserve the confidentiality of our trade secrets and operate without infringing the valid and enforceable patents and other proprietary rights of third parties. We also rely on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position in the field of AAV-based gene therapies.

We are heavily dependent on the patented or proprietary technology of third parties to develop and commercialize our products. We must obtain licenses from such third parties on commercially reasonable terms, or our business could be harmed, possibly materially. For example, we license from third parties essential parts of the therapeutic gene cassettes as well as the principal AAV vectors we use and key elements of our manufacturing process. We anticipate that we will require additional licenses in the future.

Because most patent applications throughout the world are confidential for 18 months after the earliest claimed priority date, and since the publication of discoveries in the scientific and patent literature often lags behind actual discoveries, we cannot be certain that we were the first to invent or file applications for the inventions covered by our pending patent applications. Moreover, we may have to participate in post-grant proceedings in the patent offices of the United States or foreign jurisdictions, such as oppositions, reexaminations or interferences, in which the patentability or priority of our inventions are challenged. Such proceedings could result in substantial cost, even if the eventual outcome is favorable to us.

Our intellectual property portfolio consists of owned and in-licensed patents, licenses, trademarks, trade secrets and other intellectual property rights.

Patent Portfolio

Our gene therapy programs are protected by patents and patent applications directed to various aspects of our technology. For example, our gene therapy programs are protected by patents and patent applications with composition-of-matter or method of use claims that cover the therapeutic gene, the promoter, the viral vector capsid or other specific parts of these technologies. We also seek protection of core aspects of our manufacturing process, particularly regarding our baculovirus expression system for AAV vectors in insect cells. In addition, we have filed manufacturing patent applications with claims directed to alternative compositions-of-matter and manufacturing processes to seek better protection from competitors.

We file the initial patent applications for our commercially important technologies in both Europe and the United States. For the same technologies, we typically file international patent applications under the Patent Cooperation Treaty (“PCT”) within a year. We also may seek, usually on a case-by-case basis, local patent protection in Canada, Australia, Japan, China, India, Israel, South Africa, New Zealand, South Korea and Eurasia, as well as South American jurisdictions such as Brazil and Mexico.

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Our intellectual property portfolio includes the following rights:

·                  16 patent families that we own;

·                  9 patent families that we exclusively in-license; and

·                  5 patent families that we non-exclusively in-license.

The geographic breakdown of our owned patent portfolio is as follows:

·                  11 issued U.S. patents;

·                  8 granted European Patent Office patents;

·                  2 pending PCT patent application;

·                  7 pending U.S. patent applications;

·                  11 pending European Patent Office patent applications; and

·                  36 pending and 35 granted patent applications in other jurisdictions.

The patent portfolios for our manufacturing platform and most advanced programs are summarized below.

Owned Manufacturing Patents

We own a patent family directed to large scale production of AAV vectors in insect cells. The family includes two issued patents in the United States, an issued patent in Japan and pending applications in the United States and other jurisdictions. The standard 20-year term for patents in this family will expire in 2027. This patent family relates to first-generation technology developed by uniQure and is used in Glybera.

Furthermore, we own two patent families directed to improving AAV vectors and covering AAV vectors manufactured at large scale relating to our second-generation technology used in all our other programs. One patent family contains pending applications in the United States, Europe, Japan and other jurisdictions, and issued patents in the United States, Japan, Australia, China and other jurisdictions. The standard 20-year term for patents in this family will expire in 2028. The other patent family contains an issued patent in the US and a pending patent in Europe. The standard 20-year term for patents in this family will expire in 2031.

In addition, we own a family of patent applications relating to a proprietary baculovirus removal process which contributes to obtain regulatory compliant AAV vector products. This family includes a granted patent in Europe and pending applications in the United States, Europe, Japan and other jurisdictions. The standard 20-year term for patents in this family, if issued, will expire in 2032. This patent family relates to technology used in Glybera and further product development programs.

We own a PCT-application, which covers AAV5 administration technology through intrathecally delivery routes. The standard 20-year term of patents in this family will expire in 2034.

We recently filed a patent application covering technology that is related to methods to suppress immunological responses to AAV vectors. The standard 20-year term of patents in this family will expire in 2035.

Owned Product-related Patents

S100A1

We hold patents related to our S100A1 product candidate in heart and skeletal muscle diseases. The patents have been granted in Europe, Canada, Japan and the US, the term of which will expire in 2020.

Our subsidiary uniQure GmbH has also developed and the Technology Transfer group at Heidelberg University has filed a second medical use patent application relating to the therapeutic window and effective dosages of S100A1 in heart disease. We exercised our option to license the patent in January 2017.

Glybera

We co-own with the University of British Columbia (“UBC”) a patent family relating to the lipoprotein lipase variant LPL-S447X transgene used in Glybera, including issued patents in Europe and Japan. The standard 20-year term for patents in this family will expire in 2020. UBC exclusively licensed its patent rights to Xenon, which has granted us the sublicense described below.

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Licenses

We have obtained exclusive or non-exclusive rights from third parties under a range of patents and other technology that we use in our product and development programs, as described below. Our agreements with these third parties generally grant us a license to make, use, sell, offer to sell and import products covered by the licensed patent rights in exchange for our payment of some combination of an upfront amount, annual fees, royalties, a percentage of amounts we receive from our licensees and payments upon the achievement of specified development, regulatory or commercial milestones. Some of the agreements specify the extent of the efforts we must use to develop and commercialize licensed products. The agreements generally expire upon expiration of the last-to-expire valid claim of the licensed patents. Each licensor may terminate the applicable agreement if we materially breach our obligations and fail to cure the breach within a specified cure period.

Technology Used for Multiple Programs

We are exploiting technology from the third party sources described below in more than one of our programs.

National Institutes of Health—AAV production

In 2007, we entered into a license agreement with the NIH, which we amended in 2009 and 2013. The patents under this license cover basic technology to produce AAV vectors in insect cells. Under the license agreement, the NIH has granted us a non-exclusive license to patents relating to production of AAV vectors, to make, use, sell, offer to sell and import specified plasmids, which are small DNA molecules that are physically separate from, and can replicate independently of, chromosomal DNA within a cell, or other materials, which we refer to as AAV products. We may only grant sublicenses under this agreement with the NIH’s consent, which may not be unreasonably withheld. We are exploiting this technology for our Glybera and hemophilia B programs. The standard 20-year term for the underlying patents will expire in 2022.

Payment obligations to the NIH under this license agreement include a low single-digit percentage royalty on the sale of AAV products by us or on our behalf; a maximum sub-teen double-digit percentage of sublicensing income; potential additional development milestone fees for the initiation of each clinical trial, which would total in the aggregate $0.3 million for one Phase I, Phase II and Phase III trial; potential regulatory milestone fees totaling $0.8 million for the first marketing approvals in specified countries or jurisdictions; and an annual maintenance fee of $0.01 million creditable against royalties. We do not have to pay royalties or milestone fees under this agreement if we have to pay royalties or milestone fees under our 2011 agreement with the NIH, described below, for the same product. Under the license agreement, we have agreed to meet benchmarks in our development efforts, including as to development events, clinical trials and marketing approval, within specified timeframes.

The NIH may terminate this agreement in specified circumstances relating to our insolvency or bankruptcy. We may terminate this agreement for any reason, in any territory, subject to a specified notice period.

National Institutes of Health—AAV5

In 2011, we entered into another license agreement with the NIH, superseding an earlier agreement. Under this agreement, the NIH granted us an exclusive, worldwide license to patents relating to AAV5 for use in therapeutic products to be delivered to the brain or liver for treatment of human diseases originating in the brain or liver, but excluding arthritis-related diseases, and a non-exclusive, worldwide license to patents relating to AAV5 for all other diseases, in each case to make, use, sell, offer to sell and import products within the scope of the specified patent claims. We refer to the products licensed under this agreement as AAV5 products. We may grant sublicenses under this agreement only with the NIH’s consent, which may not be unreasonably withheld. We are currently exploiting this technology for our programs on hemophilia B and Huntington’s Disease syndrome. In November 2016, we amended our exclusive license agreement with the NIH in order to explicitly indicate that the exclusive license rights for AAV5-based therapeutic products to be delivered to the brain or liver are covered by any method of administration such as direct tissue, systemic delivery or any other means.

Payment obligations to the NIH under this license agreement include royalties equal to a low single-digit percentage of net sales of AAV5 products, if any, by or on behalf of us or our sublicensees; a single to sub-teen double-digit percentage of sublicensing income; potential additional development milestone fees for the initiation of each clinical trial, which would total in the aggregate $0.3 million for one Phase I, Phase II and Phase III trial; total potential regulatory milestone fees of $1.7 million for the first marketing approvals in specified countries or jurisdictions; and an annual maintenance fee of $0.02 million creditable against royalties. If an AAV5 product is also covered by our 2007 agreement with the NIH, our obligation to pay royalties on net sales and our obligation to pay milestone fees only apply under this 2011 agreement and not the 2007 agreement. We have agreed to meet benchmarks in our development efforts, including as to development events, clinical trials and marketing approval, within specified timeframes.

The NIH may terminate this agreement in specified circumstances relating to our insolvency or bankruptcy. We may terminate this agreement for any reason, in any country or territory, subject to a specified notice period.

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Protein Sciences

In 2016, we revised our existing license contract with Protein Sciences Corporation for the use of its expresSF+ (“SF+”) insect cell line and associated technology for human therapeutic and prophylactic uses (except Influenza) to provide us with a royalty free, perpetual right and license to the licensed technology in the field of AAV-based gene therapy.

Technology Used for Specific Development Programs

Hemophilia B

St. Jude Children’s Research Hospital

In 2008, we entered into a license agreement with St. Jude, which we amended in 2012. Under the license agreement, St. Jude has granted us an exclusive license, with a right to sublicense, to patent rights relating to expression of hFIX in gene therapy vectors, to make, import, distribute, use and commercialize products containing hFIX covered by a valid patent claim in the field of gene therapy for treatment or prophylaxis of hemophilia B. In addition, we have a first right of negotiation regarding any patent applications that are filed by St. Jude for any improvements to the patent rights licensed to us. The U.S. patent rights will expire in 2028 and the European patents will expire in 2025.

We have agreed to pay St. Jude a royalty equal to a low single-digit percentage of net sales, if any, by us or our sublicensees of products covered by the licensed patent rights, and a portion of certain amounts we receive from sublicensees ranging from a mid-single digit to a mid-teen double-digit percentage of such amounts. We have also agreed to pay St. Jude one-time milestone fees totaling $0.65 million upon the achievement of specified development and regulatory milestones, and an annual maintenance fee of $0.01 million creditable against royalties and milestones in the same year. We have agreed to use commercially reasonable efforts to diligently develop and commercialize products licensed under this agreement.

The agreement will remain in effect until no further payment is due relating to any licensed product under this agreement or either we or St. Jude exercise our rights to terminate it. St. Jude may terminate the agreement in specified circumstances relating to our insolvency. We may terminate the agreement for convenience at any time subject to a specified notice period.

Huntington’s disease

Benitec, Galapagos and CSHL

In 2012, we entered into a non-exclusive license agreement with Benitec Australia Limited with the option to convert to exclusivity. Under the non-exclusive agreement, we obtain sublicensable rights to Benitec’s patented ddRNAi technology for the development, manufacturing and commercialization are limited to AAV vectors comprising the Benitec’s ddRNAi technology targeting the Huntingtin gene.

In March 2015, the agreement was amended and extended to patent rights obtained from Benitec through a sublicense derived from Galapagos. Galapagos’ technology comprises potential additional RNAi-technology to develop an AAV-vector for Huntington’s disease. Under the agreement, Benitec is eligible for specified milestone payments and single-digit royalties on products that include Benitec’s technology. In the event such products also include Galapagos’ technology, an additional low, single-digit royalty payment will be payable.

In December 2015, we have concluded a license agreement with Cold Spring Harbor Laboratory (“CSHL”). Under the agreement, CSHL has granted us an exclusive, sublicensable license to develop and commercialize Products including certain of CSHL’s patented RNAi-related technology for the treatment or prevention of Huntington’s disease.

Under the agreement, annual fees, development milestone payments and future single-digit royalties may be payable.

Glybera

We exclusively in-license from Aventis Pharma S.A., subsequently acquired by Sanofi, a patent family co-owned by UBC and Sanofi that relates to the use of AAV-LPL vectors for LPL-deficiency, including issued patents in Europe and other jurisdictions and two pending U.S. patent applications. The standard 20-year term for patents in this family expired in 2015. Product protection will be extended by this license until 2020 in those European countries where a supplementary protection certificate (“SPC”), will be granted. In some European countries, Sanofi has applied for SPCs on the basis of their patent EP0946741 and our market authorization for Glybera. In Italy, an SPC has been granted to Sanofi by the Italian Patent and Trademark Office (“PTO”) but we believe that not all of the relevant information was made known to the PTO at that time. Accordingly, we believe that the Glybera product produced by our proprietary manufacturing methods does not infringe upon the claims presented in EP0946741.

We non-exclusively in-license a patent family from the Salk Institute that relates to a genetic promoter that enhances the expression of LPL-S447X delivered to the target tissues. This family includes four issued patents in the United States that have standard 20-year terms that will expire in 2017, and issued patents in Europe and other jurisdictions that have standard 20-year terms that will expire in 2018.

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We non-exclusively in-license a patent family relating to the AAV1 capsid from AmpliPhi Biosciences, Inc. or AmpliPhi. This family includes three issued patents in the United States, and one each in Europe and Japan, as well as issued patents elsewhere and a pending application in the United States. The standard 20-year term for patents in this family will expire in 2019. The University of Pennsylvania exclusively licensed its patent rights to AmpliPhi, which has granted us a sublicense.

Trade Secrets

In addition to patents and licenses, we rely on trade secrets and know-how to develop and maintain our competitive position. For example, significant aspects of the process by which we manufacture our gene therapies are based on unpatented trade secrets and know-how. We seek to protect our proprietary technology and processes and obtain and maintain ownership of certain technologies, in part, through confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and commercial collaborator. We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by maintaining physical security of our premises and physical and electronic security of our information technology systems.

Trademarks

uniQure and Glybera are registered trademarks in various jurisdictions including the United States and the European Union. We intend to seek trade mark protection for other product candidates as and when appropriate.

Competition

The biotechnology and pharmaceutical industries, including in the gene therapy field, are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property. We face substantial competition from many different sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions and governmental agencies and public and private research institutions.

We are aware of numerous companies focused on developing gene therapies in various indications, including AGTC, Abeona Therapeutics, Adverum Biotechnologies, Asklepios BioPharmaceutical, Audentes Therapeutics, Avalanche Biotech, AveXis, Bayer, BioMarin, Bioveratiy, bluebird bio, Dimension Therapeutics, Errant Gene Therapeutics, Expression Therapeutics, Freeline Therapeutics, Genethon, Genzyme, GlaxoSmithKline, Homology Medicines, Lysogene, Megenics, Milo Therapeutics, Nightstarx, Pfizer, REGENXBIO, Renova Therapeutics, Retrosense Therapeutics, Sangamo BioSciences, Shire, Solid Biosciences, Spark Therapeutics, Takara, and Voyager, as well as several companies addressing other methods for modifying genes and regulating gene expression. Although companies and research institutions in the gene therapy field tend to focus on particular target indications, any advances in gene therapy technology made by a competitor may be used to develop therapies competing against Glybera or one of our product candidates. We may also face competition with respect to the treatment of some of the diseases that we are seeking to target with our gene therapies from protein pharmaceuticals under development at pharmaceutical and biotechnology companies such as Amgen, Bayer, Biogen, BioMarin, Genzyme, Novartis, Novo Nordisk, Pfizer, Shire, and numerous other pharmaceutical and biotechnology firms.

We also compete with existing standards of care, therapies and symptomatic treatments, as well as any new therapies that may become available in the future for the indications we are targeting.

Many of our current or potential competitors, either alone or with their collaborators, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and gene therapy industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

The key competitive factors affecting the success of all of our programs are likely to be their efficacy, safety, convenience, price and the availability of reimbursement from government and other third party payers. We also believe that, due to the small size of the patient populations in the orphan indications we target, being first to market will be a significant competitive advantage. We believe that our advantages in vector and manufacturing technology will allow us to reach market in a number of indications ahead of our competitors, and to capture the markets in these indications.

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Government Regulation and Reimbursement

Government authorities in the United States, European Union and other countries extensively regulate, among other things, the approval, research, development, preclinical and clinical testing, manufacture (including any manufacturing changes), packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, reimbursement, and import and export of pharmaceutical products, biological products and medical devices. We believe that all of our product candidates will be regulated as biological products, or biologics, and in particular, as gene therapies, and will be subject to such requirements and regulations under U.S. and foreign laws. For other countries outside of the United States and the European Union, marketing approval and pricing and reimbursement requirements vary from country to country. If we fail to comply with applicable regulatory requirements, we may be subject to, among other things, fines, refusal to approve pending applications, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Regulation in the United States

In the United States, the FDA regulates biologics under the Public Health Service Act (“PHSA”) and the Federal Food, Drug, and Cosmetic Act (“FCDA”) and regulations and guidance implementing these laws. Obtaining regulatory approvals and ensuring compliance with applicable statutes and regulatory requirements entails the expenditure of substantial time and financial resources, including payment of user fees for applications to the FDA. All of our current product candidates are subject to regulation by the FDA as biologics. An applicant seeking approval to market and distribute a new biologic in the United States must typically undertake the following:

·                  completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s current Good Laboratory Practice (“cGLP”) regulations;

·                  submission to the FDA of an Investigational New Drug (“IND”) which allows human clinical trials to begin unless the FDA objects within 30 days;

·                  approval by an independent institutional review board (“IRB”) before each clinical trial may be initiated;

·                  performance of adequate and well-controlled human clinical trials in accordance with the FDA’s or EMA’s good clinical practices (“GCP”) to establish the safety, potency, purity and efficacy of the proposed biological product for each indication;

·                  preparation and submission to the FDA of a Biologics License Application (“BLA”);

·                  payment of substantial product and establishment user fees;

·                  approval of the BLA by the FDA, in consultation with an FDA advisory committee, if deemed appropriate by the FDA;

·                  satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; and

·                  compliance with any post-approval commitments, including Risk Evaluation and Mitigation Strategies (“REMS”), and post-approval studies required by the FDA.

Human Clinical Studies in the US under an IND

Clinical trials involve the administration of the investigational biologic to human subjects under the supervision of qualified investigators in accordance with cGCP requirements. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of an IND. A clinical trial may not proceed in the US unless and until an IND becomes effective, which is 30 days after its receipt by the FDA unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. The protocol and informed consent documents must also be approved by an IRB. The FDA, an IRB, or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Information about certain clinical trials, including results, must be submitted within specific timeframes for listing on the ClinicalTrials.gov website.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

·                  Phase I: The biological product is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early understanding of its effectiveness.

·                  Phase II: The biological product is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

·                  Phase III: The biological product is administered to an expanded patient population in adequate and well-controlled clinical trials to generate sufficient data to statistically confirm the potency and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labelling of the product.

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FDA Guidance Governing Gene Therapy Products

The FDA has issued various guidance documents regarding gene therapies, which outline additional factors that the FDA will consider at each of the above stages of development and relate to, among other things, the proper preclinical assessment of gene therapies; the chemistry, manufacturing, and control information that should be included in an IND application; the design and analysis of shedding studies for virus or bacteria based gene therapies; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe delayed adverse effects in subjects who have been exposed to investigational gene therapies when the risk of such effects is high.

If a gene therapy trial is conducted at, or sponsored by, institutions receiving NIH funding for recombinant DNA research, a protocol and related documentation must be submitted to, and the study registered with, the NIH Office of Biotechnology Activities (“OBA”) pursuant to the NIH Guidelines for Research Involving Recombinant DNA Molecules prior to the submission of an IND to the FDA. In addition, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. The NIH will convene the Recombinant DNA Advisory Committee (“RAC”), a federal advisory committee, to discuss protocols that raise novel or particularly important scientific, safety or ethical considerations at one of its quarterly public meetings. The OBA will notify the FDA of the RAC’s decision regarding the necessity for full public review of a gene therapy protocol. RAC proceedings and reports are posted to the OBA web site and may be accessed by the public.

Compliance with cGMP Requirements

Manufacturers of biologics must comply with applicable cGMP regulations, including quality control and quality assurance and maintenance of records and documentation. Manufacturers and others involved in the manufacture and distribution of such products must also register their establishments with the FDA and certain state agencies. Both domestic and foreign manufacturing establishments must register and provide additional information to the FDA upon their initial participation in the manufacturing process. Establishments may be subject to periodic unannounced inspections by government authorities to ensure compliance with cGMPs and other laws. Discovery of problems may result in a government entity placing restrictions on a product, manufacturer, or holder of an approved BLA, and may extend to requiring withdrawal of the product from the market. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specification.

FDA Programs to Expedite Product Development

The FDA has several programs to expedite product development, including fast track designation and breakthrough therapy designation. Under the fast track program, the sponsor of a biologic candidate may request the FDA to designate the product for a specific indication as a fast track product concurrent with or after the filing of the IND for the product candidate. The benefits include greater interactions with the FDA, eligibility for accelerated approval based on a surrogate endpoint, eligibility for priority review of the BLA, and rolling review of sections of the BLA. The FDA may also take certain actions with respect to products designated as breakthrough therapies, including holding meetings with the sponsor and the review team throughout the development process, providing timely advice to and communication with the product sponsor regarding development and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team, and taking certain steps to design the clinical trials in an efficient manner.

Moreover, under the provisions of the Food and Drug Administration Safety and Innovation Act (“FDASIA”), enacted in 2012, a sponsor can request designation of a product candidate as a breakthrough therapy. A breakthrough therapy is defined as a product that is intended, alone or in combination with one or more other products, to treat a serious or life threatening disease or condition, and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Products designated as breakthrough therapies are eligible for the fast track program features as described above, intensive guidance on an efficient development program beginning as early as Phase 1 trials, and a commitment from the FDA to involve senior managers and experienced review staff in a proactive collaborative, cross disciplinary review.

Submission of a BLA

The results of the preclinical and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of a BLA requesting a license to market the product for one or more indications. The submission of a BLA is subject to an application user fee, currently exceeding $2.4 million, and the sponsor of an approved BLA is also subject to annual product and establishment user fees, currently exceeding $98,000 per product and $513,000 per establishment. These fees are typically increased annually. The FDA has agreed to specified performance goals in the review of BLAs.

Most such applications are meant to be reviewed within ten months from the filing acceptance date (typically 60 days after date of filing), and most applications for priority review products are meant to be reviewed within six months of the filing acceptance date (typically 60 days after date of filing). The FDA will assign a date for its final decision for the product (the PDUFA date) but can request an extension to complete review of a product application,

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The FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the biological product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter. Many drug applications receive complete response letters from the FDA during their first cycle of FDA review.

If the FDA approves a product, it may limit the approved indications for use of the product; require that contraindications, warnings or precautions be included in the product labeling; require that post-approval studies, including Phase IV clinical trials, be conducted to further assess a biologic’s safety after approval; require testing and surveillance programs to monitor the product after commercialization; or impose other conditions, including distribution restrictions or other risk management mechanisms, including Risk Evaluation and Mitigation Strategies (“REMS”). The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs.

Following approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and the FDA review and approval. The product may also be subject to official lot release, meaning that the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. Other post-approval requirements include reporting of cGMP deviations that could affect the identity, potency, purity and overall safety of a distributed product, reporting of adverse effects, reporting new information regarding safety and efficacy, maintaining adequate record-keeping, and complying with electronic record and signature requirements.

Biosimilars and Exclusivity

The Biologics Price Competition and Innovation Act of 2009 which amended the Public Health Service Act (“PHS”) authorized the FDA to approve biosimilars under Section 351(k) of the PHS. Under the Act, a manufacturer may submit an application for licensure of a biologic product that is biosimilar to or interchangeable with a previously approved biological product or reference product. In order for the FDA to approve a biosimilar product, it must find that it is highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there are no clinically meaningful differences between the reference product and proposed biosimilar product in safety, purity or potency. A finding of interchangeability requires that a product is determined to be biosimilar to the reference product, and that the product can be expected to produce the same clinical results as the reference product. An application for a biosimilar product may not be submitted to the FDA until four years following approval of the reference product, and it may not be approved until 12 years thereafter. These exclusivity provisions only apply to biosimilar companies and not companies that rely on their own data and file a full BLA. The twelve year exclusivity market period in the U.S. for biologics has been controversial and may be shortened in the future.

Orphan Drug Exclusivity

Under the Orphan Drug Act, the FDA may designate a biological product as an orphan drug if it is intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a biological product available in the United States for treatment of the disease or condition will be recovered from sales of the product. If a product with orphan designation receives the first FDA approval, it will be granted seven years of marketing exclusivity, which means that the FDA may not approve any other applications for the same product for the same indication for seven years, unless clinical superiority is demonstrated in a head-to-head trial. Competitors may receive approval of different products for the indication for which the orphan product has exclusivity and may obtain approval for the same product but for a different indication. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. The FDA has granted orphan drug designation to Glybera for treatment of LPLD, meaning that it will receive orphan drug exclusivity if it is the first product approved for that indication.

Pediatric Exclusivity

Pediatric exclusivity provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity in the US, including orphan exclusivity and exclusivity against biosimilars. This six-month exclusivity may be granted if the FDA issues a written request to the sponsor for the pediatric study, the sponsor submits a final study report after receipt of the written request, and meets the terms and timelines in the FDA’s written request.

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Regenerative Advanced Therapy Designation

The 21st Century Cures Act became law in December 2016 and created a new program under Section 3033 in which the FDA has authority to designate a regenerative therapeutic product as a regenerative advanced therapy (“RAT”) eligible for accelerated approval. A drug is eligible for a RAT designation if: 1) it is a regenerative medicine therapy which is a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except those products already regulated under Section 361 of the PHS, 2) the drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and 3) preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition. A RAT must be made with the submission of an IND or as an amendment to an existing IND. FDA will determine if a product is eligible for RAT designation within 60 days of submission.

FDA Regulation of Companion Diagnostics

We may seek to develop companion diagnostics for use in identifying patients that we believe will respond to our gene therapies. FDA officials have issued draft guidance to address issues critical to developing in vitro companion diagnostics, such as biomarker qualification, establishing clinical validity, the use of retrospective data, the appropriate patient population and when the FDA will require that the companion diagnostic and the drug be approved simultaneously. The draft guidance issued in July 2011 states that if safe and effective use of a therapeutic product depends on an in vitro diagnostic device, then the FDA generally will require approval or clearance of the diagnostic device by the Center for Devices and Radiological Health at the same time that the FDA approves the therapeutic product.

Anti-Kickback Provisions and Requirements

The U.S. federal anti-kickback statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under Medicare, Medicaid or other federally financed healthcare programs. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other. Violations of the anti-kickback statute are punishable by imprisonment, criminal fines, civil monetary penalties and exclusion from participation in federal healthcare programs. Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, the exemptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor.

Federal false claims laws prohibit any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim paid. Pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly inflating drug prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, certain marketing practices, including off-label promotion, have also been alleged by government agencies to violate false claims laws. The majority of states also have statutes or regulations similar to the federal anti-kickback law and false claims laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payer.

U.S. Foreign Corrupt Practices Act

The U.S. Foreign Corrupt Practices Act, to which we are subject, prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.

Coverage, Pricing and Reimbursement

The containment of healthcare costs has become a priority of federal, state and foreign governments, and the prices of drugs have been a focus in this effort. Third party payers are also increasingly challenging the prices charged for medical products and services and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. If these third party payers do not consider a product to be cost-effective compared to other available therapies, they may not cover the product after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit. The U.S. government, state legislatures and foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government-paid health care costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. Adoption of such controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals.

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As a result, the marketability of any product which receives regulatory approval for commercial sale may suffer if the government and third party payers fail to provide adequate coverage and reimbursement. In addition, an increasing emphasis on managed care in the United States has increased and will continue to increase the pressure on drug pricing. Coverage policies, third party reimbursement rates and drug pricing regulation may change at any time. In particular, the Patient Protection and Affordable Care Act contains provisions that may reduce the profitability of drug products, including, for example, increased rebates for drugs sold to Medicaid programs, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based on pharmaceutical companies’ share of sales to federal health care programs. Even if favorable coverage and reimbursement status is attained for one or more products that receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Regulation in the European Union

Product development, the regulatory approval process and safety monitoring of medicinal products and their manufacturers in the European Union proceed broadly in the same way as they do in the United States. Therefore, many of the issues discussed above apply similarly in the context of the European Union. In addition, drugs are subject to the extensive price and reimbursement regulations of the various EU member states. The Clinical Trials Directive 2001/20/EC, as amended (and to be replaced by the Clinical Trial Regulation EU 536/2014 in October 2018), provides a system for the approval of clinical trials in the European Union via implementation through national legislation of the member states. Under this system, approval must be obtained from the competent national authority of an EU member state in which the clinical trial is to be conducted. Furthermore, a clinical trial may only be started after a competent ethics committee has issued a favorable opinion on the CTA, which must be supported by an investigational medicinal product dossier with supporting information prescribed by the Clinical Trials Directive and corresponding national laws of the member states and further detailed in applicable guidance documents. The sponsor of a clinical trial, or its legal representative, must be based in the European Economic Area. European regulators and ethics committees also require the submission of adverse event reports during a study and a copy of the final study report.

Marketing approval

Marketing approvals under the European Union regulatory system may be obtained through a centralized or decentralized procedure. The centralized procedure results in the grant of a single marketing authorization that is valid for all—currently 28—EU member states. Pursuant to Regulation (EC) No 726/2004, as amended, the centralized procedure is mandatory for drugs developed by means of specified biotechnological processes, and advanced therapy medicinal products as defined in Regulation (EC) No 1394/2007, as amended. Drugs for human use containing a new active substance for which the therapeutic indication is the treatment of specified diseases, including but not limited to acquired immune deficiency syndrome, neurodegenerative disorders, auto-immune diseases and other immune dysfunctions, as well as drugs designated as orphan drugs pursuant to Regulation (EC) No 141/2000, as amended, also fall within the mandatory scope of the centralized procedure. Because of our focus on gene therapies, which fall within the category of advanced therapy medicinal products (“ATMPs”) and orphan indications, our products and product candidates are expected to qualify for the centralized procedure.

In the marketing authorization application (“MAA”) the applicant has to properly and sufficiently demonstrate the quality, safety and efficacy of the drug. Guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs have been issued and include, among other things, the preclinical studies required to characterize ATMPs; the manufacturing and control information that should be submitted in a MAA; and post-approval measures required to monitor patients and evaluate the long term efficacy and potential adverse reactions of ATMPs. Although these guidelines are not legally binding, we believe that our compliance with them is likely necessary to gain and maintain approval for any of our product candidates. The maximum timeframe for the evaluation of an MAA under the centralized procedure is 210 days after receipt of a valid application subject to clock stops during which the applicant deals with EMA questions.

The European Commission may grant a so-called “marketing authorization under exceptional circumstances”. Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use, because the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, or in the present state of scientific knowledge, comprehensive information cannot be provided, or it would be contrary to generally accepted principles of medical ethics to collect such information.

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Consequently, marketing authorization under exceptional circumstances may be granted subject to certain specific obligations, which may include the following:

·                  the applicant must complete an identified program of studies within a time period specified by the competent authority, the results of which form the basis of a reassessment of the benefit/risk profile;

·                  the medicinal product in question may be supplied on medical prescription only and may in certain cases be administered only under strict medical supervision, possibly in a hospital and in the case of a radio-pharmaceutical, by an authorized person; and

·                  the package leaflet and any medical information must draw the attention of the medical practitioner to the fact that the particulars available concerning the medicinal product in question are as yet inadequate in certain specified respects.

A marketing authorization under exceptional circumstances is subject to annual review to reassess the risk-benefit balance in an annual reassessment procedure. Continuation of the authorization is linked to the annual reassessment and a negative assessment could potentially result in the marketing authorization being suspended or revoked. The renewal of a marketing authorization of a medicinal product under exceptional circumstances, however, follows the same rules as a regular marketing authorization. Thus, a marketing authorization under exceptional circumstances is granted for an initial five years, after which the authorization will become valid indefinitely, unless the EMA decides that safety grounds merit one additional five-year renewal. A marketing authorization under exception circumstances will normally not lead to the completion of a full dossier and hence is unlikely to become a normal marketing authorization.

The European Union also provides for a system of regulatory data and market exclusivity. According to Article 14(11) of Regulation (EC) No 726/2004, as amended, and Article 10(1) of Directive 2001/83/EC, as amended, upon receiving marketing authorization, new chemical entities approved on the basis of complete independent data package benefit from eight years of data exclusivity and an additional two years of market exclusivity. Data exclusivity prevents regulatory authorities in the European Union from referencing the innovator’s data to assess a generic (abbreviated) application during the eight year period. During the additional two-year period of market exclusivity, a generic marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic medicinal product can be marketed until the expiration of the market exclusivity. The overall ten-year period will be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. Even if a compound is considered to be a new chemical entity and the innovator is able to gain the period of data exclusivity, another company nevertheless could also market another version of the drug if such company obtained marketing authorization based on an MAA with a complete independent data package of pharmaceutical test, preclinical tests and clinical trials. The EMA has also issued guidelines for a comprehensive comparability exercise for biosimilars, and for specific classes of biological products.

Additional rules apply to medicinal products for pediatric use under Regulation (EC) No 1901/2006, as amended. Potential incentives include a six-month extension of any supplementary protection certificate granted pursuant to Regulation (EC) No 469/2009, however not in cases in which the relevant product is designated as an orphan medicinal product pursuant to Regulation (EC) No 141/2000, as amended. Instead, medicinal products designated as orphan medicinal product may enjoy an extension of the ten-year market exclusivity period granted under Regulation (EC) No 141/2000, as amended, to twelve years subject to the conditions applicable to orphan drugs.

Manufacturing and manufacturers’ license

Pursuant to Commission Directive 2003/94/EC as transposed into the national laws of the member states, the manufacturing of investigational medicinal products and approved drugs is subject to a separate manufacturer’s license and must be conducted in strict compliance with cGMP requirements, which mandate the methods, facilities, and controls used in manufacturing, processing, and packing of drugs to assure their safety and identity. Manufacturers must have at least one qualified person permanently and continuously at their disposal. The qualified person is ultimately responsible for certifying that each batch of finished product released onto the market has been manufactured in accordance with cGMP and the specifications set out in the marketing authorization or investigational medicinal product dossier. cGMP requirements are enforced through mandatory registration of facilities and inspections of those facilities. Failure to comply with these requirements could interrupt supply and result in delays, unanticipated costs and lost revenues, and subject the applicant to potential legal or regulatory action, including but not limited to warning letters, suspension of manufacturing, seizure of product, injunctive action or possible civil and criminal penalties.

Advertising

In the European Union, the promotion of prescription medicines is subject to intense regulation and control, including a prohibition on direct-to-consumer advertising. All medicines advertising must be consistent with the product’s approved summary of products characteristics, factual, accurate, balanced and not misleading. Advertising of medicines pre-approval or off-label is prohibited. Some jurisdictions require that all promotional materials for prescription medicines be subjected to either prior internal or regulatory review & approval.

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Other Regulatory Requirements

A holder of a marketing authorization for a medicinal product is legally obliged to fulfill a number of obligations by virtue of its status as a marketing authorization holder (“MAH”). The MAH can delegate the performance of related tasks to third parties, such as distributors or marketing collaborators, provided that this delegation is appropriately documented and the MAH maintains legal responsibility and liability.

The obligations of an MAH include:

·                  Manufacturing and Batch Release. MAHs should guarantee that all manufacturing operations comply with relevant laws and regulations, applicable good manufacturing practices, with the product specifications and manufacturing conditions set out in the marketing authorization and that each batch of product is subject to appropriate release formalities.

·                  Pharmacovigilance. MAHs are obliged to establish and maintain a pharmacovigilance system, including a qualified person responsible for oversight, to submit safety reports to the regulators and comply with the good pharmacovigilance practice guidelines adopted by the EMA.

·                  Advertising and Promotion. MAHs remain responsible for all advertising and promotion of their products, including promotional activities by other companies or individuals on their behalf and in some cases must conduct internal or regulatory pre-approval of promotional materials.

·                  Medical Affairs/Scientific Service. MAHs are required to disseminate scientific and medical information on their medicinal products to healthcare professionals, regulators and patients.

·                  Legal Representation and Distributor Issues. MAHs are responsible for regulatory actions or inactions of their distributors and agents.

·                  Preparation, Filing and Maintenance of the Application and Subsequent Marketing Authorization. MAHs must maintain appropriate records, comply with the marketing authorization’s terms and conditions, fulfill reporting obligations to regulators, submit renewal applications and pay all appropriate fees to the authorities.

We hold the marketing authorization under exceptional circumstances granted for Glybera in the European Union, and we may hold any future marketing authorizations granted for our product candidates in our own name, or appoint an affiliate or a collaborator to hold marketing authorizations on our behalf. Any failure by an MAH to comply with these obligations may result in regulatory action against an MAH and ultimately threaten our ability to commercialize our products.

Reimbursement

In the European Union, the pricing and reimbursement mechanisms by private and public health insurers vary largely by country and even within countries. In respect of the public systems, reimbursement for standard drugs is determined by guidelines established by the legislator or responsible national authority. The approach taken varies from member state to member state. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed. Other member states allow companies to fix their own prices for medicines, but monitor and control company profits and may limit or restrict reimbursement. The downward pressure on healthcare costs in general, particularly prescription drugs, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products and some of EU countries require the completion of studies that compare the cost-effectiveness of a particular product candidate to currently available therapies in order to obtain reimbursement or pricing approval. Special pricing and reimbursement rules may apply to orphan drugs. Inclusion of orphan drugs in reimbursement systems tend to focus on the medical usefulness, need, quality and economic benefits to patients and the healthcare system as for any drug. Acceptance of any medicinal product for reimbursement may come with cost, use and often volume restrictions, which again can vary by country. In addition, results-based rules or agreements on reimbursement may apply.

Orphan Drug Regulation

We have been granted orphan drug exclusivity for Glybera for treatment of LPLD until October 2022, subject to the conditions applicable to orphan drug exclusivity in the European Union. Regulation (EC) No 141/2000, as amended, states that a drug will be designated as an orphan drug if its sponsor can establish:

·                  that it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the Community when the application is made, or that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the European Union and that without incentives it is unlikely that the marketing of the drug in the European Union would generate sufficient return to justify the necessary investment; and

·                  that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the European Union or, if such method exists, that the drug will be of significant benefit to those affected by that condition.

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Regulation (EC) No 847/2000 sets out further provisions for implementation of the criteria for designation of a drug as an orphan drug. An application for the designation of a drug as an orphan drug must be submitted at any stage of development of the drug before filing of a marketing authorization application.

If an EU-wide community marketing authorization in respect of an orphan drug is granted pursuant to Regulation (EC) No 726/2004, as amended, the European Union and the member states will not, for a period of 10 years, accept another application for a marketing authorization, or grant a marketing authorization or accept an application to extend an existing marketing authorization, for the same therapeutic indication, in respect of a similar drug.

This period may however be reduced to six years if, at the end of the fifth year, it is established, in respect of the drug concerned, that the criteria for orphan drug designation are no longer met, in other words, when it is shown on the basis of available evidence that the product is sufficiently profitable not to justify maintenance of market exclusivity. Notwithstanding the foregoing, a marketing authorization may be granted, for the same therapeutic indication, to a similar drug if:

·                  the holder of the marketing authorization for the original orphan drug has given its consent to the second applicant;

·                  the holder of the marketing authorization for the original orphan drug is unable to supply sufficient quantities of the drug; or

·                  the second applicant can establish in the application that the second drug, although similar to the orphan drug already authorized, is safer, more effective or otherwise clinically superior.

Regulation (EC) No 847/2000 lays down definitions of the concepts similar drug and clinical superiority, which concepts have been expanded upon in subsequent Commission guidance. Other incentives available to orphan drugs in the European Union include financial incentives such as a reduction of fees or fee waivers and protocol assistance. Orphan drug designation does not shorten the duration of the regulatory review and approval process.

Employees

As of December 31, 2016, we had a total of 251 employees. Pursuant to our previously announced strategic restructuring plan, we anticipate that we will reduce our overall headcount by approximately 50-55 positions in 2017. As of December 31, 2016, 35 employees had an M.D. or Ph.D. degree, or the foreign equivalent. We are in the process of establishing a works council in the Netherlands.

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2      Financial results

Restructuring

Following the completion of our strategic review in November 2016, we announced a restructuring plan for our operations and organization. As part of our restructuring plan, we intend to terminate between 50 and 55 non-executive employees and four executives during 2017. We accrued $1.1 million related to termination benefits offered to executive employees, expected to be paid in 2017. We also entered into termination agreements with non-executive employees in January 2017, for which the related termination benefits of $0.5 million in aggregate will be recognized over the relevant remaining service period during 2017. In addition to the cash payments of termination benefits, we incurred $0.2 million non-cash share-based payment expenses related to the accelerated vesting of performance share units granted to the terminated executives. These changes are expected to reduce annual operating expenses by $5.0 to $6.0 million from 2018 onwards.

As a result of consolidating our manufacturing activities into our Lexington site, we expect we will not utilize all of the capacity of our new Amsterdam facility, which we are obliged to rent until May 2032. While we will seek to sublet any unused capacity within our new Amsterdam facility, we concluded that the benefits of using this corporate facility are not estimable and, as such, did not recognize a loss contingency for the floors not utilized.

Extera

In December 2013, the International Court of Arbitration at the International Chamber of Commerce (“ICC”) received a formal request for arbitration from Extera Partners LLC (“Extera Partners”), alleging a fee due in respect of consulting services provided to us in connection with a partnering transaction with Chiesi Farmaceutici S.p.A. (“Chiesi”) in April 2013. In April 2016, we were notified of a partial award of the ICC. The ICC partially found in Extera Partners’ favor and held that it was entitled to $0.7 million (plus interest) in success fees in respect of consideration received to date in connection with the relevant partnering transactions. In July 2016, the ICC awarded a one-off settlement to Extera in respect of potential future revenues. In December 2016, we and Extera Partners agreed to settle the arbitration case for an amount of $2.9 million (including legal and related settlement costs). We recorded a$1.4 million provision for our estimate of legal and related settlement costs in 2015 and $1.5 million in 2016, which are presented in selling, general and administrative expenses.

Hercules Loan Facility

On May 6, 2016, we executed a second amended and restated loan agreement (the “Loan Agreement”) with Hercules Technology Growth Capital, Inc. (“Hercules”). The Loan Agreement extends the maturity date from June 30, 2018 to May 1, 2020. The Loan Agreement includes a total commitment from Hercules of up to $40.0 million, of which $20.0 million is currently outstanding. We have not drawn down any additional loan amounts under the Loan Agreement as amended. The interest rate is adjustable and is the greater of (1) 8.25% or (2) 8.25% plus the prime rate less 5.25%. Under the Loan Agreement, the interest rate will initially be 8.25% per annum with a backend fee of 4.85% and facility fee of 0.75% of the outstanding loan amounts. The interest-only payment period under the Loan Agreement is also extended and set at 18 months from May 6, 2016, but can be extended to 24 months upon us raising a cumulative $30.0 million in up-front corporate payments and/or proceeds from equity financings (the “Raisings”) and to 30 months upon us raising a cumulative $50.0 million from Raisings. The term loan will mature on May 1, 2020.

Transition to One-Tier board

At our Annual General Meeting on June 15, 2016, the shareholders resolved to amend the articles of association of uniQure by which the two-tier Management Board and Supervisory Board structure transitioned to a single Board of Directors with executive and non-executive directors. The adoption of a single Board of Directors enables us to more deeply integrate executive and non-executive board members and reflects the corporate governance standards most familiar to the majority of our shareholder base.

The shareholders also approved the proposals to:

·                  Appoint Mr. Daniel Soland, the Company’s Chief Executive Officer, and Mr. Matthew Kapusta, the Company’s Chief Financial Officer, as executive directors; and

·                  Appoint Dr. Sander van Deventer, Ms. Paula Soteropoulos, Dr. David Schaffer, Mr. Will Lewis, Mr. Philip Astley-Sparke, and Mr. Jack Kaye as non-executive directors. As part of the governance transition, Mr. Ferdinand Verdonck and Mr. Joseph Feczko resigned from the board.

Mr. Soland has subsequently left the Company and Mr. Kapusta has been appointed Chief Executive Officer.

Protein Sciences license

On June 16, 2016, we revised our existing license contract with Protein Sciences Corporation for the use of its expresSF+ (SF+) insect cell line to provide us with a royalty free, perpetual right and exclusive license to the licensed technology in the field of AAV-based gene therapy.

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Results of operations

Comparison of the twelve months ended December 31, 2016, and 2015.

Revenues

License revenues increased, as we started amortizing the non-refundable upfront payment and target designation fees received from BMS in the second and third quarter of 2015 in addition to the upfront fees received from Chiesi in 2013.

Effective May 2015, our research activities associated with S100A1 for heart failure are being conducted on behalf of BMS. During the period from May 21, 2015 to December 31, 2015, we generated $2.3 million in collaboration revenues compared to $13.0 million for the year ended December 31, 2016.

Collaboration revenue generated from our co-development of AMT-060 and services provided for Glybera for the year ended December 31, 2016, were $7.2 million, compared to $4.9 million for the year ended December 31, 2015. The fluctuation is explained by the level of out-of-pocket eligible for reimbursement by Chiesi under the co-development.

Research and Development Expenses

Research and development expenses for the year ended December 31, 2016, were $71.5 million, compared to $54.0 million for the year ended December 31, 2015.

·                      Our R&D expenses increased to $46.6 million in 2016 from $33.1 million in 2015 as result of the Phase I/II study of AMT-060 we initiated in 2014, the intensification of our activities to support the research of S100A1 following our collaboration with BMS commencing in May 2015, as well as progressing the research activities associated with AMT-130 in Huntington’s disease and our collaboration with 4D to develop next-generation vector serotypes;

·                      We incurred operating expenses related to the build-out and certification of our Lexington plant of $20.7 million in 2016 compared to $15.5 million in 2015;

·                      We incurred operating expenses related to the rental of temporary research space in Amsterdam (beginning in October 2015) and the build out of our new facility in Amsterdam (commencing in March 2016). These expenses were $4.4 million in 2016 compared to $1.1 million in 2015;

·                      We recorded $1.1 million in termination benefits related to our restructuring announced in November 2016;

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·                      We recorded $0.1 million in 2016 and $1.4 million in 2015 in share-based compensation expenses related to our collaboration with 4D Molecular Therapeutics, which commenced in January 2014; and

·                      We recorded a gain related to the change in fair value of the contingent consideration owed to the sellers of InoCard of $1.1 million in 2016 compared to a loss of $1.3 million in 2015.

Selling, General and Administrative Expenses

Selling, general and administrative expenses for the year ended December 31, 2016, were $25.9 million, compared to $21.2 million for the year ended December 31, 2015.

·                      Our expenses related to employees, contractors and consultants in 2016 were $10.6 million compared to $12.0 million in 2015. Our general and administrative costs increased in 2016 and 2015 due to our investments in finance, information technology and human resources to accommodate the growth in our employee base and strengthening of our operating processes and internal controls over financial reporting;

·                      We incurred $2.1 million of share-based compensation payments in 2016 compared to $3.5 million in 2015;

·                      We incurred $5.9 million of professional fees in 2016 compared to $6.4 million in 2015. We regularly incur accounting, audit and legal fees associated with operating as a public company. In addition, we incurred significant fees in 2016 related to the conversion of our financial reporting from IFRS to U.S. GAAP, as well as fees associated with the Extera arbitration proceedings and the refinancing of our loan facility in May 2016. In 2015, we incurred legal fees related to the Extera arbitration proceedings, the closing of our follow-on offering in April 2015, the completion of the BMS transaction in May 2015 as well as advisory fees to enhance our internal controls over financial reporting;

·                      Following the commencement of Glybera commercialization in September 2015, we incurred costs associated with the Glybera global registry and Phase IV study as selling cost (previously, these costs were classified as R&D expenses). In 2016 we incurred $3.2 million of such expenses compared to $0.7 million for the four month period from September to December 2015; and

·                      We incurred costs related to the partial award and settlement of the Extrera arbitration proceedings of $1.5 million in 2016 compared to $1.4 million in 2015.

Impairment loss

In 2015 we recorded an $13.0 million impairment loss after our distribution partner Chiesi disclosed certain reimbursement-related developments that are expected to have an adverse impact on the future cash flows generated by the commercialization of Glybera. The impairment loss was recorded in relation to capitalized development cost and certain other related intangible assets. In 2016, we fully wrote-off the remaining $0.5 million carrying amount of Glybera intangibles.

Finance income / (expense) - net

Our Finance income / (expense), net, for the years ended December 31, 2016, and 2015 was as follows:

Our interest income consists of interest income earned on our cash and cash equivalents.

We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S. dollars. We recognize foreign exchange losses and gains related to changes in these foreign currencies. We recognized a net gain of $1.0 million in the year ended December 31, 2016, compared to a net loss of $2.2 million for 2015.

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We issued warrants to Hercules in 2013 and to BMS in 2015. We recognize changes in the fair value of these warrants within finance income / (expense). In the year ended December 31, 2016, we recognized a gain of $0.9 million compared to a gain of $0.5 million in 2015.

During 2016, an amount of $2.2 million, compared with $2.4 million for 2015, was recorded as interest expense in relation to the Original, the 2014 Amended and the 2016 Amended Facility.

Corporate income taxes

During 2015, we transferred intangible assets to a Dutch entity. Given their history of losses, the Dutch entities do not recognize deferred tax assets. Following the transfer, we released the deferred tax liability related to the transferred intangible assets to profit and loss.

Cash Flow and Cash Position

As of December 31, 2016, we had cash and cash equivalents of $132.5 million. We expect cash and cash equivalents to fund operations into 2019. The table below summarizes our consolidated cash flow data for years ended December 31:

We have incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Therapeutics (“AMT”) Holding N.V. in 1998. We had a net loss of $71.4 million in 2016 and $80.6 million in 2015. As of December 31, 2016, we had an accumulated deficit of $388.6 million.

Net Cash (used in)/generated by operating activities

Net cash used in operating activities was $72.2 million for the year ended December 31, 2016, compared to $23.1 million of cash generated for the year ended December 31, 2015.

Our cash generated in the year ended December 31, 2015, includes a $50.0 million upfront payment received from BMS following the inception of our collaboration in May 2015 and a $15.0 million payment in August 2015 associated with the designation of the second, third and fourth collaboration targets. Excluding these payments, our cash used in operating activities was $72.2 million for the year ended December 31, 2016, compared to $41.9 million in 2015.

The increase in cash used in operating activities during the year ended December 31, 2016, reflects $5.2 million (2015: $8.6 million) of additional expenditures related to the certification and operation of our Lexington facility; $0.5 million (2015: $4.0 million) of additional expenditures related to our preclinical product candidates (the portion that is not funded by our collaboration partners), offset in part by a reduction of $1.9 million in expenditures related to our quality management systems and organization (2015: increase of $6.6 million).

In 2016, we also made a $2.9 million payment related to the settlement of the Extera arbitration.

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Net cash used in investing activities

In 2016, we used $17.8 million in our investing activities compared to $11.4 million in 2015.

In 2016, we invested $13.0 million in our new facility in Amsterdam (including a $0.6 million deposit) and $1.9 related to an exclusive license from Protein Science Corporation.

In 2015, we invested $2.8 million to upgrade our Amsterdam manufacturing facility and our temporary research facility in Amsterdam.

Net cash generated from financing activities

During the year ended December 31, 2016, we received $2.6 million from the exercise of options to purchase ordinary shares in relation to our share incentive plans, compared to $2.9 million in the year ended December 31, 2015.

We received net proceeds associated with the issuance of shares to BMS of $37.6 million in June 2015 and $37.9 million in August 2015.

We received net proceeds of $82.5 million associated with our follow-on offering in April 2015.

Equity

Shareholders’ equity at December 31, 2016, amounted to $63.6 million compared to $128.7 million for December 31, 2015; a total of 25.3 million shares were issued and outstanding at December 31, 2016.

We had a net loss of $71.4 million in 2016 and $80.6 million in 2015. As of December 31, 2016, we had an accumulated deficit of $388.6 million.

Outlook 2017

In 2017 we plan to:

·                  Drive our hemophilia B program towards late stage clinical development;

·                  Continue non-clinical and preclinical studies that are expected to support an IND filing for the S100A1 gene therapy program for the treatment of congestive heart failure, which is currently being developed with BMS;

·                  Advance multiple research programs related to gene therapy candidates targeting liver-directed and CNS disorders;

·                  Continue IND-enabling studies for our gene therapy program for the treatment of Huntington’s disease; and

·                  Implement our strategic restructuring which includes the consolidation of GMP manufacturing into our Lexington site; and

·                  Recruit senior management and build out our clinical, medical and regulatory capabilities, primarily in the U.S.

We believe our cash-on-hand of $132.5 million as of December 31, 2016, will be sufficient to fund operations into 2019 as we intend to significantly reduce capital expenditures in 2017 and 2018 and realize operational cost savings from the strategic restructuring initiated in November 2016.

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3                                         Risk Factors

The business is exposed to specific industry risks, as well as general business risks. The following discussion summarizes our strategic, operational, financial, financial reporting and compliance risks. The risks faced by uniQure during 2016 are not limited to this list; more information on risks we are exposed to is available in notes 3 and 4 to our consolidated financial statements and a more comprehensive description of the risks below and others can be found in our Annual Report filed on Form 10-K for the year ending December 31, 2016, which was filed with the Securities Exchange Commission on March 15, 2017, and a copy of which is available from our website.

a)                                                 Risks Related to the Development of Our Product Candidates

·                  We may encounter substantial delays in and impediments to the progress of our clinical trials or fail to demonstrate the safety and efficacy of our product candidates.

·                  Our progress in early-stage clinical trials may not be indicative of long-term efficacy in late-stage clinical trials, and our progress in trials for one product candidate may not be indicative of progress in trials for other product candidates.

·                  Fast track product, breakthrough therapy, priority review, or RAT designation by the FDA for our product candidates may not lead to faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.

·                  We may not be successful in our efforts to use our gene therapy technology platform to build a pipeline of additional product candidates.

·                  Our strategy of obtaining rights to key technologies through in-licenses may not be successful.

·                  Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product candidates or adversely affect our ability to conduct our business or obtain marketing approvals for our product candidates.

b)                                                 Risks Related to Our Manufacturing

·                  Delays in qualifying our U.S. manufacturing facility for clinical production activities could delay our development and commercialization plans and thereby limit our revenues and growth.

·                  Our manufacturing facilities are subject to significant government regulations and approvals. If we fail to comply with these regulations or maintain these approvals our business will be materially harmed.

·                  Gene therapies are complex and difficult to manufacture. We could experience production or technology transfer problems that result in delays in our development or commercialization schedules or otherwise adversely affect our business.

·                  Our use of viruses, chemicals and other hazardous materials requires us to comply with regulatory requirements and exposes us to significant potential liabilities.

c)                                                  Risks Related to Regulatory Approval

·                  We cannot predict when or if we will obtain marketing approval to commercialize a product candidate.

·                  The FDA will require us to conduct comparability studies evaluating the products manufactured at our Amsterdam facility with those to be manufactured at our new Lexington, Massachusetts facility. Those studies and their results could substantially delay or preclude our ability to commercialize our product candidates in the United States.

·                  The risks associated with the marketing approval process are heightened by the status of our products as gene therapies.

·                  Our failure to obtain or maintain orphan product exclusivity for any of our product candidates for which we seek this status could limit our commercial opportunity, and if our competitors are able to obtain orphan product exclusivity before we do, we may not be able to obtain approval for our competing products for a significant period of time.

·                  As appropriate, we intend to seek all available periods of regulatory exclusivity for our product candidates. However, there is no guarantee that we will be granted these periods of regulatory exclusivity or that we will be able to maintain these periods of exclusivity.

·                  We are subject to costly post-approval obligations, review and other regulatory requirements for Glybera in the European Union.

d)                                                 Risks Related to Our Dependence on Third Parties

·                  If our collaboration with BMS is not successful or if BMS designates or develops fewer targets than permitted under our collaboration agreement, our development plans, financial position and opportunities for growth may be adversely affected.

·                  We rely on third parties for important aspects of our development programs. If these parties do not perform successfully or if we are unable to maintain any of our collaboration arrangements, or enter into new collaborations, our business could be adversely affected.

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e)                                                  Risks Related to Our Intellectual Property

·                  We rely on licenses of intellectual property from third parties, and such licenses may not provide adequate rights or may not be available in the future on commercially reasonable terms or at all, and our licensors may be unable to obtain and maintain patent protection for the technology or products that we license from them.

·                  Our intellectual property licenses with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of our rights to the relevant intellectual property or technology or increase our financial or other obligations to our licensors.

·                  If we fail to comply with our obligations in our intellectual property licenses with third parties, we could lose rights that are important to our business.

·                  If we are unable to obtain and maintain patent protection for our technology and products, or if the scope of the patent protection is not sufficiently broad, our ability to successfully commercialize our products may be impaired.

·                  We may become involved in lawsuits to protect or enforce our patents or other intellectual property or third parties may assert their intellectual property rights against us, which could be expensive, time consuming and unsuccessful.

·                  Our reliance on third parties may require us to share our trade secrets, which could increase the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.

f)                                                   Risks Related to Our Financial Position and Need for Additional Capital

·                  We have incurred significant losses to date, expect to incur losses over the next several years and may never achieve or maintain profitability.

·                  We will likely need to raise additional funding, which may not be available on acceptable terms, or at all. Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations which could have a material adverse effect on our business, financial conditions, results of operations and cash flows.

·                  Our existing and any future indebtedness could adversely affect our ability to operate our business

·                  We may be required to sublease space in excess of our requirements at our Amsterdam site.

g)                                                 Risks Related to Other Legal Compliance Matters

·                  Our relationships with customers and third party payers will be subject to applicable anti-kickback, anti-bribery, fraud and abuse and other laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

·                  If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.

·                  Product liability lawsuits could cause us to incur substantial liabilities and to limit commercialization of our therapies.

h)                                                 Risks Related to Employee Matters and Managing Growth

·                  Our future success depends on our ability to retain key executives and technical staff and to attract, retain and motivate qualified personnel.

·                  We have initiated a restructuring of our operations, as a result of which we will reduce our overall headcount in the Netherlands while continuing to expand our key capabilities in the United States and, as a result, may encounter difficulties associated with organizational change.

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i)                                         Internal risk management and control system

We have developed an internal risk management and control system that is tailored to the risk factors that are relevant to us. Our controls frequently entail involvement of the Board and Senior Management. The internal risk management and control systems were discussed in the Board.

The Board is responsible for designing, implementing and operating our internal risk management and control systems. The objective of these systems is to manage in an effective and efficient manner the significant risks to which we are exposed. Our internal risk management and control systems are designed to provide reasonable assurance that these objectives are met. Such systems can never provide absolute assurance regarding achievement of our objectives, nor can they provide absolute assurance that material errors, losses, fraud, and the violation of laws or regulations will not occur. A summary of the risks that could have prevented us from realizing our objectives is included in the section ‘Risk Factors’ of this report.

Our internal risk management and control systems make use of various measures including:

·                  Annual strategic evaluations of the business;

·                  Periodic operational review meetings of the Leadership Team comprising the executive directors of the Board and Senior Management;

·                  Quarterly review of the financial position and prospects as part of the Board meeting;

·                  A planning and control cycle consisting of annual, quarterly and monthly procedures, including subsequent follow-up on achievements of targets set;

·                  A system of internal controls and procedures;

·                  An Audit Committee that meets regularly with the executives and Senior Management as well as the independent auditors.

We maintain records and procedures designed to:

·                  Ensure that records are maintained, in reasonable detail, accurately and fairly reflect the transactions and disposition of the assets of the Company;

·                  Provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with IFRS, and that receipts and expenditures of the Company are being made only by authorized employees in accordance with documented authorizations; and

·                  Provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of the Company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness for future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with policies or procedures may deteriorate.

Based on the evaluation of our Company’s disclosure controls and procedures as of December 31, 2016, our chief executive officer and interim chief financial officer concluded that our company’s disclosure controls and procedures were effective.

Director’s Annual Report on Internal Control Over Financial Reporting

The Board is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act. This rule defines internal control over financial reporting as a process designed by, or under the supervision of, a company’s chief executive officer and chief financial officer and effected by the Board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles and includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of our assets that could have a material effect on the financial statements.

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We assessed the effectiveness of our internal control over financial reporting as of December 31, 2016. This assessment was performed under the direction and supervision of our chief executive officer and chief financial officer, and based on criteria established in Internal Control—Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO). Our Board’s assessment of the effectiveness of our internal control over financial reporting included testing and evaluating the design and operating effectiveness of our internal controls. In our Board’s opinion, we have maintained effective internal control over financial reporting as of December 31, 2016, based on criteria established in the COSO 2013 framework.

Remediation Plan Measures

During 2016, we implemented remediation measures to resolve a material weakness resulting from a lack of segregation of duties, which we had identified as of December 31, 2015. Our remediation measures included the enforcement of IT access controls related to financial reporting critical applications, the removal of excessive access rights of finance staff to critical IT applications, the segregation of preparatory and review tasks, enabled by the addition of finance and accounting staff, the removal of rights to enter information into our financial reporting system for staff approving bank payments.

We have completed the testing and evaluation of the design and operating effectiveness of the controls, and concluded that the previously reported material weakness has been remediated as of December 31, 2016.

Additional information

The Consolidated Financial Statements for 2016 of the uniQure Group prepared in accordance with U.S. GAAP were also filed with the U.S. Securities and Exchange Commission on March 15, 2017, as part of our Annual Report on Form 10-K for the year ended December 31, 2016, which is available on the Company’s website. Additional information required by Dutch law for the Dutch Statutory Annual Report of uniQure is set out within this document.

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4      Governance and compliance

We monitor and assess applicable Dutch and U.S., corporate governance codes, rules, and regulations. We are subject to the 2008 Dutch Corporate Governance Code (the “Code”), as we are a listed company with its statutory seat in the Netherlands. As a Company listed on the NASDAQ Global Select Market (“NASDAQ”) we also are required to comply with U.S. securities laws, including the U.S. Exchange Act, the U.S. Sarbanes-Oxley Act of 2002, as well as NASDAQ listing rules, and the rules and regulations promulgated by the U.S. Securities and Exchange Commission (“SEC”).

Our corporate governance structure is based on the requirements of the Dutch Civil Code, the company’s Articles of Association and the rules and regulations applicable to companies listed on the NASDAQ. These procedures include a risk management and control system, as well as a system of assurance of compliance with laws and regulations.

When in this chapter a reference is made to Articles of Association, this shall be a reference to the Company’s Articles of Association, as adopted on June 16, 2016.

The consolidated financial statements for 2016 of uniQure were also filed with the U.S. Securities and Exchange Commission on March 15, 2017, as part of our Annual Report on Form 10-K for the year ended December 31, 2016, which is available on our website. Additional information required by Dutch law for the Annual Report is set out within this document.

a)             Board

At our Annual General Meeting on June 15, 2016, the shareholders to amend the articles of association of uniQure by which the two-tier Management Board and Supervisory Board structure transitioned to a single Board of Directors with executive and non-executive directors. The adoption of a single Board of Directors enables the Company to more deeply integrate executive and non-executive board members and reflects the corporate governance standards most familiar to the majority of its shareholder base.

At the June 2016 Annual General Meeting the shareholders also approved the proposals to:

·                  Appoint Mr. Daniel Soland, the Company’s Chief Executive Officer, and Mr. Matthew Kapusta, Chief Financial Officer, as executive directors; and

·                  Appoint Dr. Sander van Deventer, Ms. Paula Soteropoulos, Dr. David Schaffer, Mr. Will Lewis, Mr. Philip Astley-Sparke, and Mr. Jack Kaye as non-executive directors;

All members of the Board, both the executive directors and the non-executive directors, are collectively responsible for the management performed by the one-tier Board and the general policy and strategy of the Company. The executive directors manage the day-to-day management of the Company. The non-executive directors focus on the supervision on the policy and functioning of the executive directors and the general state of affairs within the Company. The Board is supported by a Secretary, who is appointed by the Board. The executive directors and non-executive directors are appointed as such by the General Meeting at the binding nomination of the non-executive directors. The General Meeting may at all times overrule a binding nomination by a resolution adopted by at least a two thirds majority of the votes cast, provided such majority represents more than half the issued share capital. The Board determines the number of executive directors and non-executive directors, provided that the number of executive directors shall at all times be less than the number of non-executive directors. Only natural persons can be non-executive director. The General Meeting shall at all times be entitled to suspend or dismiss a board member. The Board shall also at all times be entitled to suspend (but not dismiss) an executive director.

The Board shall appoint an executive director as chief executive officer (CEO). The Board shall furthermore appoint a non-executive director to be Chairman of the Board for such period as the Board may decide.

The Board, as well as two executive directors acting jointly, are authorized to represent uniQure externally.

Any newly appointed director of the Board will serve for a maximum of four years and unless a director resigns earlier, his term shall end at the close of the annual General Meeting of Shareholders to be held in the fourth year after the year of his appointment. A director of the Board may be reappointed.

The Articles of Association provide that the Board shall draw up a retirement schedule for the directors of the Board.

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The following table sets out information with respect to the executive and non-executive directors of the Board, and their ages and position at uniQure as of the date of this annual report. The business address of our management board members is our registered office address at Meibergdreef 61, Amsterdam 1105 BA, the Netherlands.

1)             As of March 31, 2017

Matthew Kapusta, Matthew Kapusta, age 44, joined uniQure as our chief financial officer in January 2015 and was elected to our Management Board at the 2015 annual general meeting. In December 2016 he was appointed our chief executive officer.  Prior to joining uniQure, Mr. Kapusta was Senior Vice President at AngioDynamics from 2011 to 2014, responsible for corporate development, strategic planning and national accounts. Prior to AngioDynamics, he served as Vice President, Finance for Smith & Nephew Orthopaedics. Mr. Kapusta’s career also includes more than a decade of investment banking experience focused on emerging life sciences companies. Mr. Kapusta was Managing Director, Healthcare Investment Banking at Collins Stewart, and held various positions at Wells Fargo Securities, Robertson Stephens and PaineWebber. Mr. Kapusta holds a Master of Business Administration from New York University’s Stern School of Business, a Bachelor of Business Administration from University of Michigan’s Ross School of Business and earned his Certified Public Accountant license in 1996 while at Ernst & Young.

Philip Astley-Sparke, Philip Astley-Sparke, age 45, has served as a member of our Board since June 2015 and as chairman since 2016. He was previously president of uniQure Inc. from January 2013 until February 2015 and was responsible for building uniQure’s US infrastructure. Mr. Astley-Sparke is currently Executive Chairman and co-founder of Replimune Limited, a company developing second-generation oncolytic vaccines. Mr. Astley-Sparke served as vice president and general manager at Amgen, Inc., a biopharmaceutical company, until December 2011, following Amgen’s acquisition of BioVex Group, Inc., a biotechnology company, in March 2011. Mr. Astley-Sparke had been President and Chief Executive Officer of BioVex Group, which developed the first oncolytic vaccine to be approved in the western world following the approval of Imlygic in 2015. He oversaw the company’s relocation to the U.S. from the UK in 2005. Prior to BioVex, Mr. Astley-Sparke was a healthcare investment banker at Chase H&Q/Robert Fleming and qualified as a Chartered Accountant with Arthur Andersen in London. Mr Astley-Sparke has been a venture partner at Forbion Capital Partners, a venture capital fund, since May 2012 and serves as Chairman of the Board of Oxyrane, a biotechnology company.

Dr. Sander van Deventer, Dr. Sander van Deventer, age 62, has served as a member of our Board since April 2012 and served as member of the AMT supervisory board from April 2010 to April 2012. Dr. van Deventer was one of our co-founders. He served as our interim Chief Executive Officer from February to October 2009. He has been Professor of Translational Gastroenterology at the Leiden University Medical Center since 2008 and is a partner of Forbion Capital Partners, which he joined in 2006. He serves on the boards of enGene Inc., Argos Biotherapeutics, gICare Pharma Inc and Hookipa Biotech. He was previously a professor, head of the department of experimental medicine and chairman of the department of gastroenterology of the Academic Medical Center at the University of Amsterdam from 2002 to 2004, and subsequently professor of experimental medicine at the University of Amsterdam Medical School until 2008. Dr. van Deventer is currently a professor at Leiden University Medical Center. He has more than 15 years of experience in biotechnology product development. He is the author of more than 400 scientific articles in peer-reviewed journals, and he serves as an advisor to regulatory authorities including the EMA and FDA. Dr. van Deventer holds a degree in medicine as well as a Ph.D. from the University of Amsterdam.

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David Schaffer, David Schaffer, age 49, has served as a member of our Board since January 2014. Dr. Schaffer is Professor of Chemical and Biomolecular Engineering, Bioengineering, and Neuroscience at University of California Berkeley, a position he has held since 2007, as well as Director of the Berkeley Stem Cell Center since 2011. Dr. Schaffer is also co-founder of 4D Molecular Therapeutics, a company specializing proprietary technology for gene therapy products. We entered into a collaboration and license agreement with 4D Molecular Therapeutics in January 2014. Previously, Dr. Schaffer was Assistant Professor from 1999 to 2005 and Associate Professor from 2005 to 2007 at the University of California, Berkeley Department of Chemical Engineering & Helen Wills Neuroscience Institute. He has served on the boards of the American Society for Gene and Cell Therapy and the Society for Biological Engineering. He has more than 20 years of experience in chemical and molecular engineering, and stem cell and gene therapy research, has over 165 scientific publications, and serves on 5 journal editorial boards and 5 industrial scientific advisory boards. Dr. Schaffer holds a bachelor of science degree in Chemical Engineering from Stanford University and a Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology.

Paula Soteropoulos, Paula Soteropoulos, age 49, has served as a member of our Board since July 2013. Ms. Soteropoulos is president and chief executive officer of Akcea Therapeutics, a position she has held since January 2015. From July 2013 to December 2014, she served as Senior Vice President and General Manager, Cardiometabolic Business and Strategic Alliances at Moderna Therapeutics Inc. Prior to this Ms. Soteropoulos worked at Genzyme Corporation, a biotechnology company, from 1992 to 2013, most recently as Vice President and General Manager, Cardiovascular, Rare Diseases. Ms. Soteropoulos holds a bachelor of science degree in chemical engineering and a master of science degree in chemical and biochemical engineering, both from Tufts University, and holds an executive management certificate from the University of Virginia, Darden Graduate School of Business Administration. Ms. Soteropoulos serves on the Advisory Board for the Chemical and Biological Engineering Department of Tufts University.

Will Lewis, Will Lewis, age 48, has served as a member of our Board since June 2014. Mr. Lewis is currently President, Chief Executive Officer and member of the Board of Directors of Insmed, a biopharmaceutical company specialized in inhalation therapies for orphan lung diseases. Prior to joining Insmed in 2012, he was President and Chief Financial Officer of Aegerion Pharmaceuticals, Inc., which he also co-founded. At Aegerion, he played a pivotal role in reorienting the company’s strategy to focus on orphan disease indications. He previously worked in the U.S. and Europe in investment banking for JP Morgan, Robertson Stephens and Wells Fargo. During his time in banking, he was involved in a broad range of domestic and international capital raises and advisory work valued at more than $20 billion. He serves on the Board of Directors of Oberlin College and is a member of the Visiting Committees of the Weatherhead School of Management of Case Western Reserve University and The Hawken School. He holds a B.A. from Oberlin College and an M.B.A./J.D. from Case Western Reserve University.

Jack Kaye, Jack Kaye, age 73, has served as a member of our Board since 2016. Mr. Kaye has also served as Chairman of the Audit Committee of Keryx Biopharmaceuticals, Inc. since 2006 and is currently chairman of the Audit Committee and a member of the Compensation Committee of Dyadic International, Inc. Mr. Kaye began his career at Deloitte LLP, an international accounting, tax and consulting firm, in 1970, and was a partner in the firm from 1978 until May 2006. At Deloitte, he was responsible for servicing a diverse client base of public and private, global and domestic companies in a variety of industries. Mr. Kaye has extensive experience consulting with clients on accounting and reporting matters, private and public debt financings, SEC rules and regulations and corporate governance/Sarbanes-Oxley matters. Prior to retiring, Mr. Kaye served as Partner-in-Charge of Deloitte’s Tri-State Core Client practice, a position he held for more than 20 years. Mr. Kaye has a Bachelor of Business Administration from Baruch College and is a Certified Public Accountant.

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Meetings and board committees

We have established an audit committee, a remuneration committee and a nominating and corporate governance committee. We have adopted a charter for each of these committees.

Meetings

In 2016, the Board, and prior to the transition to the single Board, the Supervisory Board held five in person meetings and one meeting by means of a conference call. During these meetings and also in informal communications among its members, extensive discussions were held to ensure the continuity of high-level management of the Company. The Chairman sets the agenda and ensures that the directors receive accurate information in time. During these formal meetings and discussions, the Board primarily focuses on the objectives and strategy of uniQure, the main risks of its business, the assessment made by the executive directors of the design and effectiveness of the internal risk management and control systems, the progress made on clinical development, corporate governance, the financial budgets the operational plan and the annual and quarterly consolidated financial statements.

Throughout 2016, the Board actively reviewed the progress and planning for the hemophilia B and Huntington’s disease program, as well as our collaboration with BMS. During the second half of 2016, the Board extensively discussed aspects related to the Company’s leadership transition, elements of the company-wide strategic review and executive recruiting and retention.

Attendance at the Board meetings during 2016 was as follows:

(1): Mr Philip Astley-Sparke was appointed Chairman of the Board effective September 21, 2016

Audit Committee

Our audit committee consists of our non-executive directors Mr. Lewis, Ms. Soteropoulos and Mr. Kaye (Chairman), who joined the Audit Committee following his appointment as non-executive director of the Board at the Annual General Meeting. Mr. Kaye succeeded Mr. Lewis as Chairman, who remained on the Committee as a member. Mr. Verdonck resigned from the Committee upon his resignation as member of the Supervisory Board as of June 15, 2016. Each member satisfies the independence requirements of the NASDAQ listing standards, and Mr. Verdonck and Mr. Kaye qualify as an audit committee financial expert, as defined in Item 9A of Form 10-K and as determined by the Board. The audit committee oversees our accounting and financial reporting processes and the audits of our consolidated financial statements. The audit committee is responsible for:

·                  Recommending the selection of our independent registered public accounting firm;

·                  Reviewing with the Company’s independent registered public accounting firm the procedures for and results of their audits;

·                  Reviewing with the independent accountants and management our financial reporting, internal controls and internal audit procedures;

·                  Reviewing and approving related party transactions; and

·                  Reviewing matters relating to the relationship between the Company and our independent registered public accounting firm, including the selection of and engagement fee for our independent registered public accounting firm, and assessing the independence of the independent registered public accounting firm.

The Audit Committee has the authority to engage independent legal, accounting and other advisers, as it determines necessary to carry out its duties. The audit committee met six times during 2016. During these meetings, the committee discussed the (interim) financial statements, the actual financial results of each of the quarters as well as the audit approach and the budget 2017

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Remuneration Committee

Our remuneration committee consists of our non-executive directors Mr. van Deventer (Chairman) and Mr. Lewis. Mr. Verdonck resigned from the Committee upon his resignation as member of the Supervisory Board as of June 15, 2016. Each member satisfies the independence requirements of the NASDAQ listing standards. The remuneration committee assists the Board in reviewing and approving or recommending our compensation structure, including all forms of compensation relating to our non-executive and executive directors as well as senior management. Members of our senior management (other than the General Counsel) may not be present at any committee meeting while the compensation of our executive directors is deliberated.

Subject to the terms of the remuneration policy approved by our General Meeting and as required by Dutch law, the remuneration committee is responsible for:

·                  Reviewing and approving or recommending to the Board for approval, as appropriate, the compensation of our executive officers following consideration of corporate goals and objectives relevant to such executive officers;

·                  Overseeing the evaluation of the Company’s senior executives;

·                  Reviewing and making recommendations to the Board regarding incentive compensation and equity-based plans; and

·                  Administering our stock option plans.

·                  The Remuneration Committee has the authority to retain compensation consultants and other outside advisors to assist in the evaluation of executive officer compensation.

The Remuneration committee met six times during 2016. The committee discussed the amendment of the 2014 Option plan, the conditions of the long-term incentive awarded in 2016, the revision of the Remuneration Policy, the compensation terms of our newly recruited executives, the terms and conditions of the termination agreements of our executive and non-executive employees leaving in 2017 and assessed the Company’s 2016 financial performance in relation to the performance units issued in 2016 as well as in relation to the 2016 short-term incentive plan.

Nominating and Corporate Governance Committee

Our nominating and corporate governance committee consists of our non-executive directors Mr. Lewis (Chairman), Mr. Astley-Sparke (until December 2016) and Mr. van Deventer (since December 2016). Mr. Feczko resigned from the Committee upon his resignation as member of the Supervisory Board as of June 15, 2016. Except for Mr. Astley-Sparke, each member satisfies the independence requirements of the NASDAQ listing standards. The nominating and corporate governance committee assists the board in selecting individuals qualified to serve as an executive or non-executive director of the board and in determining the composition of the board and its committees. The nominating and corporate governance committee is responsible for, among other things:

·                  Identifying individuals qualified to become Board members and to recommend to the Board the nominees for director at annual general meetings of Shareholders;

·                  Recommending to the Board nominees for each Committee; developing and recommending to the Board corporate governance principles applicable to the Company; and

·                  Leading the Board in its annual review of the Board’s performance.

The nominating and corporate governance committee met three times during 2016. The committee discussed the replacement of our previous CEO and the appointment of our current CEO as well as the selection of new non-executive members.

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b)             Corporate governance

In addition to U.S. securities laws, the NASDAQ listing standards and rules and regulations as promulgated by the SEC, as a Dutch company, our governance practices are governed by the 2008 Dutch Corporate Governance Code (the “Code”) a copy of which is available at www.commissiecorporategovernance.nl. The Code contains a number of principles and best practices. The Code, in contrast to U.S. laws, rules and regulations, contains an apply-or-explain principle, offering the possibility to deviate from the Corporate Governance Code and still be in compliance as long as any such deviations are explained. In certain cases, we have not applied the Code’s practices and provisions and in those instances we explain the non-application.

We conduct our operations in accordance with internationally accepted principles of good governance and best practice, while ensuring compliance with the corporate governance requirements applicable in the countries in which we operate. There is considerable overlap between the requirements we must meet under U.S. rules and regulations and the provisions of the Code and we apply most of the provisions of the Code. For clarity purposes, we have listed below deviations from the Code and our reasons for deviating.

II.2.4.       If options are granted, they shall, in any event, not be exercised in the first three years after the date of granting. The number of options to be granted shall be dependent on the achievement of challenging targets specified beforehand.

The stock options we grant to our executive and non-executive directors of the Board and to our senior management are exercisable before the third anniversary of the date of grant, which is contrary to best practices provision II.2.4 of the Code. The vesting terms of options vary between one and four years, and begin vesting on the first anniversary of date of grant. We believe our vesting schedules are in line with the practices of our peer group used for executive compensation purposes and necessary to attract and retain the best people.

II.2.5.      Shares granted to management board members without financial consideration shall be retained for a period of at least five years or until at least the end of the employment, if this period is shorter. The number of shares to be granted shall be dependent on the achievement of challenging targets specified beforehand.

The restricted stock units (“RSU”) we granted to one of our former Chief Executive Officer Mr. Aldag, vested after two years. The vesting of these RSUs was not contingent upon performance criteria. Generally, the performance stock units (“PSU”) we grant to senior management are contingent upon achieving specified performance criteria, which are approved by the Board, and any earned shares shall not vest until the third anniversary of the grant date. We believe this compensation practice is in line with the practices of our peer group. In September 2016, we granted our Chief Executive Officer a special grant of PSUs contingent upon certain performance criteria established by the Board. Any shares earned shall vest on December 31, 2017.

II.2.7          Neither the exercise price of options granted nor the other conditions may be modified during the term of the options, except in so far as prompted by structural changes relating to the shares or the company in accordance with established market practice.

By fully accelerating options in restricted cases as part of the termination agreements of certain employees in 2016, we modified the conditions of specific equity grants during the term. We believe these modifications allowed us to achieve the required transformation of the Company.

II.2.12   The remuneration report of the supervisory board shall contain an account of the manner in which the remuneration policy has been implemented in the past financial year, as well as an overview of the remuneration policy planned by the supervisory board for the next financial year and subsequent years. The report shall explain how the chosen remuneration policy contributes to the achievement of the long-term objectives of the company and its affiliated enterprise in keeping with the risk profile. The report shall be posted on the company’s website.

The Company has not posted a comprehensive report on its website. We engaged an independent, third-party compensation expert to benchmark our remuneration of executive directors and senior management compared to our peer group. Based on this evaluation, we believe our compensation is in line with market practice.

II.2.13 The overview referred to in best practice provision II.2.12 shall in any event contain the following information: items (a) — (j)

The disclosures set out under Note 19 of the consolidated financial statements cover to a large extent the above requirements. As for the year ended December 31, 2016, the Company was a listed company at NASDAQ. The disclosures made by the Company under the applicable listing rules and which are published at http://www.sec.gov are deemed to be appropriate in this respect.

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III.2.1. All supervisory board members, with the exception of not more than one person, shall be independent within the meaning of best practice provision III.2.2.

Two members of the Board of Directors are affiliated with Forbion and are therefore not independent within the meaning of the Code. The Company feels this deviation is justified both by their specific knowledge and experience of the Company’s business as well as the significant ownership interest Forbion has in the Company.

III.5.4 The Audit Committee shall in any event focus on supervising the activities of the management board with respect to …

c) compliance with recommendations and observations of internal and independent auditors;

d) the role and functioning of the internal audit function;

The Company feels that its financial reporting is sufficiently monitored by its Audit Committee and has not appointed an internal auditor.

III.7.1 A supervisory board member may not be granted any shares and/or rights to shares by way of remuneration.

The Company granted options, RSUs and PSUs (only to an executive director) to the chairman and other members of the Supervisory Board. uniQure believes that such remuneration is in accordance with the NASDAQ corporate governance requirements and market practice among companies listed in the U.S. uniQure may in the future grant equity to attract and ensure the continued services of the best qualified persons for the Board of Directors. The number of equity rights granted to each director of the Board is assessed in accordance with the Remuneration Policy as adopted by the General Meeting of shareholders. uniQure therefore believes that applying this provision of the Code is not in its best interests.

IV.1.4 The policy of the company on additions to reserves and on dividends (the level and purpose of the addition to reserves, the amount of the dividend and the type of dividend) shall be dealt with and explained as a separate agenda item at the general meeting.

The Company is not permitted by law to pay dividends because it has no retained profits on account of its history of making losses. Therefore, the Company does not intend to discuss the dividend policy at the General Meeting as a separate agenda item.

IV.3.1 Meetings with analysts, presentations to analysts, presentations to investors and institutional investors and press conferences shall be announced in advance on the website and by means of press releases. Provision shall be made for all shareholders to follow these meetings and presentations in real time, for example by means of web casting or telephone lines. After the meetings, the presentations shall be posted on the company’s website.

uniQure announces by press release most corporate presentations held at investor conferences and provides for real time participation via webcast. However, considering uniQure’s size, it would create an excessive burden to provide such access for all investor and analyst meetings and presentations, referred to in the best practice provision. uniQure endeavors to facilitate its shareholders by announcing its business updates on its website and follow such updates, to the extent possible via webcast. uniQure does not issue press releases as a standard practice. uniQure will undertake that presentations are posted on its website immediately after the meetings in question..

IV.3.4 Analysts meetings, presentations to institutional or other investors and direct discussions with the investors shall not take place shortly before the publication of the regular financial information (quarterly, half-yearly or annual reports).

The Company maintains an active program of meetings with investors, which it considers to be in the best interests of the Company and its shareholders. From time to time, these meetings may take place shortly before the publication of regular financial information, but in such circumstances no price-sensitive or material nonpublic information is disclosed.

IV.3.13 The company shall formulate an outline policy on bilateral contacts with the shareholders and publish this policy on its website.

The Company has not formulated such a policy and therefore does not comply. The Company regularly meets with shareholders in one-on-one situations, which it considers to be in the best interests of the Company and its stakeholders. In such meetings no price-sensitive or material, non-public financial information shall be disclosed.

V.3.1 The external auditor and the audit committee shall be involved in drawing up the work schedule of the internal auditor. They shall also take cognizance of the findings of the internal auditor.

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Reference is made to the explanation given in relation to best practice provision III.5.4.

V.3.3. If there is no internal audit function, the audit committee shall review annually the need for an internal auditor. Based on this review, the supervisory board shall make a recommendation on this to the management board in line with the proposal of the audit committee, and shall include this recommendation in the report of the supervisory board.

The audit committee meets with the executive directors of the Board prior to the release of the publicly disclosed financial reports, which enables the audit committee to monitor the quality and the completeness of such reports. The audit committee did not formally review the need for an internal auditor.

Gender Diversity

In 2015, Dutch law required companies whose boards do not meet a 30% gender diversity quota to disclose the reason for not having the specified diversity percentage as well as their efforts and intent to obtain such diversity. The Company’s Board currently consists of seven members, one of whom is female. The Board does not believe that increasing its size solely to meet the gender diversity requirement is in the best interest of the Company or its stakeholders. Members of the Board were and will continue to be chosen from based on their job responsibilities, regardless of gender.

c)              Related party transactions

Details of transactions between the Company and members of the Board of Directors and significant shareholders are set out in Note 18 to the consolidated financial statements and are within the meaning of best practice provisions II.3.2, II.3.3, II.3.4, III.6.1, III.6.2 III.6.3 and III.6.4 of the Dutch Corporate Governance Code. There have been no material transactions with shareholders holding more than ten percent of the shares in the Company.

d)             Functioning of the Board of Directors

The members of the Board have discussed their individual functioning, as well as that of the Board as a whole, on a continuing basis. In these discussions, also consideration was given to the composition and profile of the Board, as well as the functioning of its members and committees and the Board’s tasks. The profile sets out the types of expertise the Board must possess. In our view the Board satisfies the defined requirements, and we consider the composition to be adequate for the proper performance of its duties. The Board has appointed from among its members three separate committees with special tasks, the Audit Committee, the Remuneration Committee and the Nominating and Corporate Governance Committee. These committees prepare the decision making of the Board on the relevant matters. The following regulations can be found on the Company’s website: Corporate Governance Guidelines, Disclosure Policy, Insider Trading Policy, Code of Business Conduct and Ethics, Related Party Transaction Policy, Audit Committee Charter, Remuneration Committee Charter and Nominating and Corporate Governance Committee Charter.

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e)              Compensation of the Directors of the Board

This report sets out the remuneration policy operated by the Company in respect of the Board.

It is our aim to encourage and reward superior performance by the members of the Board with that performance being measured against achieving corporate goals, strong financial performance and the delivery of value to shareholders.

The Remuneration Committee believes that the current policy retains and motivates the Board appropriately while enforcing a strong pay for performance culture within the company. The Remuneration Committee continues to review the policy on an annual basis to ensure that it is in line with the Company’s objectives and shareholders’ interests.

Details of amounts paid, including the granted Restricted Stock Units (RSUs) to the Executive directors and to the senior management team of the Company are set out in Note 10 to the consolidated financial statements.

Salary

Base salaries are reviewed annually and revised salaries take effect from the start of the financial year. The review process is managed by the Remuneration Committee which each year assesses the market competitiveness of pay primarily in terms of total remuneration, with less emphasis on base salary.

Bonuses

The target bonus for Mr. Kapusta under his employment contract is equal to 40% of base salary. The performance criteria determining the actual level of bonus payable are set by the Board on the recommendation of the Remuneration Committee, by reference to the achievement of the Company’s goals and his individual objectives for the year.

Share Options

The Company grants share options to members of the Board and employees to primarily reward performance, provide retention and enable valued employees and directors to share in the success of the Company. These options are granted under the Company’s share incentive plan.

Board’s Share Options, RSUs and PSUs

Details of Board’s share options, RSUs and PSUs are set out in Note 10 to the consolidated financial statements.

Pensions

Starting in 2016, the Company operates a qualified 401(k) Plan for all employees including its Chief Executive Officer at its Lexington, Massachusetts facility in the USA, which offers both a pre-tax and post-tax (Roth) component. Employees may contribute up to 50% of their pre-tax compensation, which is subject to IRS statutory limits for each calendar year. The Company matches $0.50 for every $1.00 contributed to the plan by participants, up to 6% of base compensation.

f)               Financial statements

The Annual Accounts have been prepared by our CEO and discussed within the Board. The Report of the Independent Auditor, PricewaterhouseCoopers Accountants N.V., is included in the ‘Other Information’ on page 92. The financial statements are being presented for adoption by shareholders at the Annual Meeting. The Board recommends that shareholders adopt these financial statements.

g)             Shareholders and the general meeting of shareholders

The annual General Meeting of Shareholders shall be held within six months after the end of each financial year. The Company’s financial year is equal to a calendar year. The Board or those who are authorized by law or pursuant to the articles of association of the Company may convene the annual General Meeting of Shareholders.

An Extraordinary General Meeting of Shareholders may be convened by the Board or by those who are authorized by law or pursuant to the articles of association of the Company.

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In accordance with Dutch law and the articles of association, shareholders representing alone or in aggregate at least one-tenth of the Company’s issued and outstanding share capital can petition a court for authorization to convene a General Meeting of Shareholders after first requesting the Company to convene a general meeting.

A record date shall apply to establish which shareholders are entitled to attend and vote in the General Meeting of Shareholders. Such record date has been set by the Dutch Civil Code on the twenty-eighth day prior to the date of the meeting.

Each of uniQure’s shares is entitled to one vote. Shareholders may vote by proxy. The voting rights attached to any of the shares held by the Company are suspended as long as they are held in treasury.

Decisions of the General Meeting of Shareholders are taken by a simple majority of votes cast, unless Dutch law or the articles of association of the Company provide otherwise.

Amendment of the Articles of Association

The General Meeting of Shareholders may resolve to amend the articles of association at the proposal of the Board.

Issuance of ordinary shares and options

The General Meeting of Shareholders, following a proposal by the Board, is authorized to issue shares or grant rights thereto. Following a proposal by the Board the General Meeting of Shareholders can delegate this authority to the Board. On June 15, 2016, the General Meeting of Shareholders delegated the authority to the Board to issue ordinary shares in the share capital of the Company and to grant rights to subscribe for ordinary shares and to limit or exclude pre-emptive rights in connection therewith:

·                  For a period of 18 months with effect from June 15, 2016. The number of ordinary shares to be issued shall be limited to (i) the authorized share capital of the Company pursuant to the Company’s articles of association in the event of an authorized public offering, or (ii) a maximum of 19.9% of the Company’s aggregate issued capital at the time of issuance (less any shares previously issued pursuant to such authority) in connection with other issuances; and

·                  To issue ordinary shares and to grant rights to subscribe for up to 5,601,471 shares under the 2014 Share Incentive Plan.

Pre-emptive rights

Dutch law and the Articles of Association give shareholders pre-emptive rights to subscribe on a pro rata basis for any issue of new shares or upon a grant of rights to subscribe for shares. Such pre-emptive rights do not apply, however, in respect of: (i) shares issued for a non-cash contribution; (ii) shares issued to the Company’s employees; and (iii) shares issued to persons exercising a previously granted right to subscribe for shares.

On June 15, 2016, the General Meeting of Shareholders delegated the authority to issue ordinary shares in the share capital of the Company and to grant rights to subscribe for ordinary shares to the Board for a period of 18 months with effect from June 15, 2016, and to limit or exclude pre-emptive rights in connection therewith. On June 15, 2016, the General Meeting of Shareholders designated the Board as the competent body to issue ordinary shares and to grant rights to subscribe for shares under the 2014 Share Incentive Plan, Amended and Restated effective June 15, 2016, and to limit or exclude pre-emption rights in connection therewith. This authority is limited to a maximum of 1,531,471 shares.

Acquisition of own shares

The Company may acquire its own fully paid shares at any time for nil consideration (om niet). Furthermore, subject to certain provisions of Dutch law and the articles of association, the Company may acquire fully paid shares in the Company’s own capital, within the limits set by Dutch law.

Unless for nil consideration, shares may only be acquired subject to a resolution of the Board and authorized by the General Meeting of Shareholders. Such authorization from the General Meeting of Shareholders for the acquisition of the Company’s shares shall specify the number of shares that may be acquired, the manner in which these shares may be acquired and the price range within which shares may be acquired. Such authorization shall be valid for a period of not more than 18 months and may be extended from time to time for a period of not more than 18 months. On June 15, 2016, the General Meeting of Shareholders furthermore authorized the Board to acquire the Company’s own fully paid ordinary shares up to a maximum of ten percent of the Company’s issued share capital within the limits set by Dutch law and the Company’s articles of association through purchase on the public market or otherwise at a purchase price between the nominal value of the ordinary shares concerned and an amount equal to 110% of the highest price officially quoted for the ordinary shares on any of the official stock markets on which the Company’s ordinary shares are listed during any of 30 banking days preceding the date the repurchase is effected or proposed.

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No authorization from the General Meeting of Shareholders is required for the acquisition of fully paid shares for the purpose of transferring these shares to employees under a scheme applicable to such employees. Any shares the Company held in its own capital may not be voted or counted for voting quorum purposes.

Reduction of share capital

Subject to Dutch law, the General Meeting of Shareholders may resolve to reduce the Company’s issued and outstanding share capital by (i) amending the Articles of Association to reduce the nominal value of the shares or (ii) canceling:

·                  shares which the Company holds itself in the Company’s share capital, or

·                  all issued shares against repayment of the amount paid on those shares.

Dividends and other distributions

The Board may determine which part of the profits shall be added to the reserves. The part of the profit remaining after reservation shall be at the disposal of the General Meeting, which may resolve to carry it to the reserves or to distribute it among the Shareholders.

Under the Articles of Association, the Company may make distributions of profit to the Company’s shareholders after adoption of the Company’s annual accounts demonstrating that such distributions are legally permitted. With due observance of applicable law and the articles of association, the Board may resolve to make interim distributions to the Shareholders.

The General Meeting of Shareholders may, at the proposal of the Board, resolve to distribute to the Shareholders a dividend in the form of shares in the share capital of the Company. Each of the Company’s shares entitled its holder to equal ranking rights to dividends and other distributions.

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5                                         Statement of the Board of Directors

The Board of Directors is responsible for the preparation of the Annual Accounts and the Annual Report of uniQure N.V. for the year ended December 31, 2016, in accordance with applicable Dutch law and International Financial Reporting Standards (“IFRS”) as adopted by the European Union, (“EU”).

RESPONSIBILITY STATEMENT PURSUANT TO SECTION 5:25C PARAGRAPH 2(C) OF THE DUTCH FINANCIAL MARKETS SUPERVISION ACT (‘Wet op het financieel toezicht’)

Each of the Directors of the Board confirms that to the best of his or her knowledge:

·                  the uniQure N.V. 2016 Annual Accounts give a true and fair view of the assets, liabilities, financial position and profit or loss of uniQure N.V. and the entities included in the consolidation;

·                  the uniQure N.V. 2016 Annual Report gives a true and fair view of the state of affairs on December 31, 2016, the course of business during the financial year of uniQure N.V. and of the entities affiliated to it whose data are included in the 2016 Annual Accounts and that the 2016 Annual Report describes the substantial risks with which uniQure N.V. is confronted

Amsterdam, April 14, 2017

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B             Consolidated Financial Statements of uniQure N.V. for the year ended December 31, 2016

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uniQure N.V.

Consolidated Statements of Financial Position

The accompanying notes are an integral part of these consolidated financial statements.

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uniQure N.V.

Consolidated Statements of Profit or Loss and Other Comprehensive Income