Hello, and Welcome to the Annual General Meeting of Shareholders of uniQure N.V. Please note that today's meeting is being recorded. Also, there may be forward-looking statements made during this meeting, which are subject to a safe harbor as provided in the slide presentation. We will not receive any questions through our site, so it is now my pleasure to turn today's meeting over to David Meek, the Chair of the Board of Directors at uniQure. Mr. Meek, the floor is yours.
Good afternoon. My name is David Meek, Chairman of uniQure's Board of Directors, and it is my pleasure to welcome you to the 2022 Annual General Meeting of Shareholders of uniQure N.V. We are holding this year's AGM virtually in accordance with the Dutch emergency legislation related to the COVID-19 pandemic. We announced this on Wednesday, May 14th, in the Dutch newspaper and on our uniQure website. On our website, we have provided additional information regarding the conduct of the meeting. The key differences for this meeting compared to our typical prior shareholder meetings are that the shareholders are not attending in person and will not be able to vote their shares during this meeting.
I would also like to point out that those who return the proxy solicited by uniQure have authorized the persons named in the proxy, Matthew Kapusta and Dave Cerveny, to vote on the proposition coming before the meeting. Please note that unlike the format of our prior in-person meetings, if you have previously submitted a proxy, including over the Internet or by phone, your vote at this virtual meeting cannot be revoked. In the proxy materials, shareholders were invited to submit questions regarding the agenda items in advance of the meeting and no later than 11:59 P.M. Central European Time on June 13, 2022. However, we have not received any questions in advance of the meeting, and therefore, we will not be answering any questions at this meeting.
Before proceeding to the business of the meeting, I would like to take a moment to introduce those who participate in this meeting. On behalf of uniQure's board, we have Matthew Kapusta, our Chief Executive Officer and an executive member of the Board of uniQure. Also, from our board, we have Madhu Balachandran, who is the Chair of our Compensation Committee, Rachelle Jacques, who is a member of our Audit Committee, Robert Guth, who is a member of our R&D Committee, Jack Kay, who is the Chair of our Audit Committee and a member of our Compensation Committee, Leonard Post, who is the Chair of our R&D Committee, Paula Soteropoulos, who is a member of our Nominating and Governance Committee and our Research and Development Committee, Jeremy Springhorn, who is the Chair of our Nominating and Corporate Governance Committee and a member of our Audit Committee.
We also have several representatives of the company attending today. David Cerveny, our Chief Legal Officer and Secretary to the Board, who will serve as Secretary of this meeting. Christian Klemt, our Chief Financial Officer. Maria Cantor, our Chief Corporate Affairs Officer. Chiara Russo, our Director of Investor Relations and Communications. Charlotte Jane Sweeney, Legal Counsel to uniQure. Matthijs van Logeren, Chief Legal Counsel at uniQure. Bas Geerling, representing our auditor KPMG. Gijs Schouten, also from KPMG. And finally, Bart Kock, representing the Dutch notary firm, Oostinga, Matthijssen & Kock in Amsterdam, which has been retained by uniQure to assist with the voting and administration of today's meeting. Mr. Cerveny will now provide a summary of the shares represented by proxy at this meeting.
This meeting is being held pursuant to the notice given to each shareholder of record at the close of business on May 17th, 2022. Notice of the meeting was also filed with the Securities and Exchange Commission and posted on our website at www.uniqure.com on approximately April twenty-ninth, 2022. To be counted at this AGM, the ordinary shares were required to be voted in advance of this meeting by the deadline of twelve noon Central European Time on June fourteenth, 2022. The shares represented at the meeting are 38,907,334 ordinary shares, representing approximately 83% of the outstanding voting shares of uniQure. This represents a quorum as required by the company's articles of association.
Consequently, all announced proposals shall be approved by a majority of our ordinary shares voted in advance of the meeting, except where law or the company's articles of association provide other than a majority.
On behalf of the Board of Directors of uniQure, I would like to express my appreciation to all shareholders who returned their proxies and especially to all shareholders who have taken the time to join us today. Agenda items two and three are the report on the financial year of 2021 and remuneration. At this time, I would like to give the floor to Matthew Kapusta, our Chief Executive Officer, to discuss our second and third agenda items, the report on the financial year of 2021, the review of the application of our remuneration policy. Matt, the floor is yours.
Thanks, David, and good morning and good afternoon, everyone. As I look back at 2021, it was no doubt a very challenging year on multiple fronts for the global markets and the biotech community in particular. Despite that, I am really pleased with the execution for uniQure that is a reflection of all the hard work and dedication from our employees. Across our top two priorities are our clinical programs in hemophilia B and Huntington's disease. Most recently, our partner, CSL Behring, submitted both an MAA and a BLA in the European Union and the United States. That represents our second registration for an AAV gene therapy over the history of the company.
That reflects really strong clinical data that includes 18 months of follow-up from the largest clinical study within hemophilia B of an AAV gene therapy. This also triggered a $55 million additional milestone payment that we have received as a result of this progress. In Huntington's disease, which is a really exciting opportunity across a large clinical unmet need, we provided a clinical update from our phase I, phase II study in the United States, and have now enrolled a total of 32 patients across two phase I, phase II studies in the United States and Europe. We expect to have 12-month follow-up data from all patients in our low-dose cohort of the U.S. study before the end of this quarter.
We have a really exciting research pipeline that is largely focused on liver-directed disorders and CNS diseases, and last year announced four new research programs in temporal lobe epilepsy, Parkinson's disease, Alzheimer's, and ALS. We anticipate initiating IND-enabling studies across our temporal lobe epilepsy and Fabry programs in the second half of this year that we hope will support IND submissions in 2023, and look forward to starting new programs within those core areas of focus. Most importantly, our manufacturing and technology platform that really supports all of our activities. We completed process validation for our hemophilia B program last year that helped us move forward with our license applications. We're building out a second manufacturing facility that will complement large-scale commercial manufacturing here in the United States.
That second facility will be based in Amsterdam, and continue to make meaningful investments to support our leadership position in CMC, capabilities. Next slide, please. Just in terms of hemophilia B, let me just give an overview of, what we feel is really compelling clinical data. As I mentioned, this is the largest, clinical study in hemophilia B of any gene therapy, and, this included 54 patients and 18 months of follow-up. This study has met its primary endpoint of non-inferiority and also met a secondary endpoint that demonstrated statistical superiority in reducing bleeding rates compared to the gold standard of high-dose factor IX replacement therapy. We've demonstrated stable and durable FIX activity with a mean of 37%, which is in a functionally curative range.
We've demonstrated, I think, quite importantly, the ability to have a clinical benefit in nearly all patients, irrespective of preexisting neutralizing antibodies, at a range that we expect to be able to have clinical benefit in more than 95% of patients with hemophilia B. Most importantly, the therapy with more than five years of follow-up data really across our clinical development program, has been demonstrated to be well-tolerated, with over 80% of the adverse events considered mild. On the following slide is just a high-level overview of some of the clinical data. The most important takeaway is that in the most conservative way that we look at clinical benefit, which is evaluating all bleeds that have been reported by patients, we have shown that there's a 64% reduction after the one-time administration of our hemophilia B AAV gene therapy.
Looking at other factors that are important, particularly, from a healthcare economic perspective, looking at treated bleeds, there's been a 77% reduction. Then looking at spontaneous bleeds and joint bleeds between a 70%-80% reduction. On the following slide, one of the key questions that have been discussed and evaluated in the clinical community and the patient communities is the durability of these one-time administered gene therapies. On this slide, page nine, you can see the factor nine activity at various different measurements over the course of that 18-month period of time, and you can see very remarkably stable levels of factor nine activity across the patients within our clinical study. On the following page, this just reflects what we feel is a landmark collaboration with a global commercial partner in CSL Behring.
We announced this collaboration approximately two years ago. We were able to close the transaction last year. Just to remind everybody, this is one of the largest single product collaborations within the AAV gene therapy space announced to date. It included $450 million that we received upfront. As I mentioned, we also triggered another $55 million milestone payment with the submissions of the BLA and the MAA earlier this year. We have the ability to receive another $1.6 billion and receive double-digit royalties up to the low 20% on net sales. We're really pleased with having CSL as a partner. They are one of the largest players within the hemophilia and thrombosis space.
They have been in this space for three decades and with $1 billion of revenue across more than 80 countries. We're very pleased and look forward to continuing to work with them to make this product special for patients. On the following page is a summary about our progress in Huntington's disease. Huntington's is one of the most devastating disorders that affects some of the largest populations of patients when we look at rare monogenic diseases. There's approximately 50,000 patients that have been genetically confirmed to have Huntington's in the United States and Europe, and probably a lot more that actually have the disease but have chosen not to be reported or to be diagnosed because there are currently no disease-modifying treatment options available for these patients. Next slide, please.
We are really excited about our one-time administered gene therapy that has the potential to transform the lives of these patients and their families that are affected by this disease. One of the key differentiating factors associated with our therapy is that, number one, it is one time, potentially one time administered with long-term durable effects. Number two, we are administering this directly into the brain, deep within the brain, where the disease is known to manifest, and targeting suppression of the mutant protein that causes the disease somewhere between 25% and 75%. Next page, please. We have a comprehensive phase 1/2 clinical development program that we're well underway in conducting.
That includes a controlled, double-blinded, and randomized phase I/phase II dose-ranging clinical study being conducted in the United States in 26 patients, as well as an open-label study, also dose ranging, being conducted in the European Union in 15 patients. Next slide, please. The clinical study in the United States is completely and fully enrolled. All 26 patients are now included in the study. We announced at the end of last year early initial data on our first four patients within the study. The first four patients included two patients that were treated with AMT-130, as well as two patients that were in the control group that received an imitation surgical procedure. Most importantly, this data update suggested that the therapy was well-tolerated with no significant safety issues related to AMT-130.
We looked at various different biochemical biomarkers, and we were able to show that NfL, which is a biomarker that is a measure of brain injury, increased as expected after the surgical procedure to infuse AMT-130, and then by 12 months was returning to baseline. Measurements related to the levels of mutant protein in the cerebrospinal fluid will be presented on the first full cohort later on this quarter, as I mentioned. There was also no evidence of any structural abnormalities in investigating the MRI images of the patients treated with AMT-130.
On the following page, this shows that we are really at the cusp of what is going to be a very exciting next 18 months with significant data that is going to be read out from this study that really started with a broad-level clinical update at the end of last year on the first four patients. It will continue in the coming weeks with an update on the 10 patients in the low-dose cohort in the U.S. study. Then we will have much more robust complete data by the middle of next year that should include information, biomarkers, functional outcomes, efficacy data on 32 patients across both the U.S. and the European study by the middle of 2023.
Very exciting program, very high unmet need with significant data that will be read out over the course of the next 12-18 months. This is really the tip of the iceberg for us at uniQure. We have a really exciting pipeline, as I mentioned, that is really focused on liver-directed disorders, CNS diseases, as well as cardiovascular and muscle diseases, particularly through our collaboration with Bristol Myers Squibb. We look forward to providing a more fulsome update across our pipeline later on this year. In terms of financial results, the most important part of this is really our cash position. We are in a strong financial position with significant resources that have been largely supplemented through our collaboration with CSL Behring.
We ended last year with $556.3 million of cash on hand with $100 million of long-term debt that we've had on our balance sheet for quite some time that we expect the cash on hand to fund operations into the first half of 2024, and that excludes all additional economics that we may receive from our collaboration with CSL Behring. On the following page just represents our statement of operations. The revenue in 2021 was largely driven by our collaboration with CSL Behring that was closed in the middle of last year. Our total operating expenses were approximately $224 million for the year of 2021. Finally, just a couple of comments on remuneration.
Remuneration is something that we work on very closely with our compensation committee. We ensure that our remuneration is based and rooted in market best practices. That it is also rooted in pay for performance. That is focused on aligning interest of management with our shareholders, and that we are attracting and retaining talent, which is really the heart and soul of our company here at uniQure. With that, I will hand it over to David Meek to talk about some of the voting proposals.
Thank you, Matt. At this time, we will begin discussing the various proposals presented in our notice of annual general meeting and proxy statement. These corresponded to agenda items four through 11. There are nine voting proposals that we will review today. Each of these items is more fully described in our notice of annual general meeting and proxy statement. Copies of which we made available to all shareholders and are available at this meeting via the company's website and the Computershare platform that we are using for this meeting. For each voting proposal, we will announce the voting instruction received for the relevant proposal. Because all voting was conducted prior to the meeting, these instructions represent the final results for each proposal, subject to the receipt of any votes finally submitted by mail and final verification and certification by Mr. K ock, who is serving as the notary for this meeting. Voting proposal number one, adoption of the 2021 annual accounts and treatment of the results. The first proposal to be acted upon by the shareholders is the adoption of the annual accounts for the 2021 financial year and the treatment of the accumulated deficit of uniQure. The annual accounts were prepared by the board in accordance with the Articles of Association and applicable law and audited, and the board was provided with the auditor's report by KPMG Accountants N.V., uniQure's external auditor. The auditor's report begins on page 125 of the 2021 annual report. uniQure's Audit Committee also reviewed and discussed the audited financial statement with uniQure's management and auditor. The board unanimously recommends a vote for the proposal.
The board statement in support of this proposal appears in uniQure's proxy statement beginning on page five, as well as in other materials that uniQure has sent to shareholders. We will now announce the results of the vote on the proposal. I
n accordance with all the received voting instructions and pending certification of the vote, with 38,839,449 votes for, 29,224 votes against, and 38,641 votes abstained, the proposal is adopted.
Voting proposal number two, discharge of liability of the members of the Board of Directors. The second proposal to be acted upon by the shareholders is approval to grant discharge of liability to the members of the Board of Directors for the management and conduct of policy during the 2021 financial year, as far as the exercise of such duties is reflected in the 2021 annual report or otherwise disclosed to the general meeting. There are no additional matters to disclose at this time. The Board unanimously recommends a vote for the proposal. The Board statement in support of this proposal appears in uniQure's proxy statement beginning on page six, as well as in other materials that uniQure has sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all the received voting instructions and pending certification of the vote, with 31,690,450 votes for, 105,628 votes against, and 40,331 votes abstained, with 7,070,921 non-cast votes, the proposal is adopted.
The third proposal to be acted upon by the shareholders is the reappointment of Matthew Kapusta as Executive Director of the Board. Based on the nomination of the Nominating and Corporate Governance Committee, the board has unanimously resolved to reappoint Mr. Kapusta as Non-Executive Director of the Board, effective as of the close of this meeting for a three-year term ending at the end of the annual general meeting of shareholders of the company in 2025. Mr. Kapusta has served as a member of our board since June 2016. Mr. Kapusta holds options to purchase ordinary shares in the capital of the company and has been granted restricted share units. Details of his biography and equity holdings are listed in our proxy statement.
The board believes that Mr. Kapusta is qualified to serve on the board of directors as an executive director due to his broad expertise and experience in the biotechnology industry. The board unanimously recommends a vote for the appointment of Mr. Kapusta as an executive director. The board statement in support of this proposal appears in uniQure's proxy statement beginning on page 6, as well as in other materials that uniQure has sent to shareholders. We will now announce the results of the two votes on the proposal.
In accordance with all voting instructions and pending certification of the vote, with 31,703,305 votes for, 126,166 votes against, 6,942 votes abstained, and 7,070,921 non-cast votes, the proposal is adopted.
The fourth proposal to be acted upon by the shareholders is the reappointment of Robert Guth as non-executive director of the board. Based on the nomination of the Nominating and Corporate Governance Committee, the board has unanimously resolved to reappoint Dr. Guth as non-executive director of the board, effective as of the close of this meeting for a three-year term ending at the end of the annual general meeting of shareholders of the company in 2025. Dr. Guth has served as a member of the board in various capacities since June 2018 and serves on our Research and Development Committee. Dr. Guth holds options to purchase ordinary shares in the capital of the company and has been granted restricted share units. Details of his biography and equity holdings are listed in our proxy statement.
The board believes that Dr. Guth is qualified to serve on the board of directors as non-executive director due to his extensive experience in the biotechnology industry. The board unanimously recommends a vote for the appointment of Dr. Guth as a non-executive director. The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page 6, as well as in other materials that uniQure sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all received voting instructions and pending certification of the vote with 31,637,586 votes for, 190,982 votes against, 7,845 votes abstained, and 7,070,921 non-cast votes, the proposal is adopted.
The fifth proposal to be acted upon by the shareholders is the renewal of the designation of the board as the competent body to issue ordinary shares and to grant rights to subscribe for ordinary shares up to a max of the authorized share capital of uniQure in the event of an underwritten public offering or a maximum of 19.9% of the aggregate issued share capital of the company at the time of issuance in connection with any other single issuance or series of related issuances for a term of 18 months with effect from the date of this meeting. The existing authorization expires on December sixteenth, 2022, and it is common practice for Dutch companies to seek to renew this authorization annually on a rolling basis.
The approval of this voting proposal will maintain flexibility to allow the board to issue ordinary shares without the delay and expense of calling extraordinary general meetings of shareholders. The designation can be used for all purposes, subject to statutory limitations and except for awards granted under the 2014 Share Incentive Plan. The board unanimously recommends a vote for the proposal. The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page eight, as well as in other materials that uniQure sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all the received voting instructions and pending certification of the vote, with 22,030,987 votes for, 16,865,228 votes against, 11,119 votes abstained, the proposal is adopted.
The sixth proposal to be acted upon by the shareholders is the renewal of the designation of the board as a competent body to limit or exclude preemptive rights in connection with the issuance of ordinary shares of uniQure and granting of the rights to subscribe for ordinary shares. Under Dutch law, holders of our ordinary shares would have a pro rata preemptive right of subscription to any of our ordinary shares issued for cash. A preemptive right of subscription is the right of our current shareholders to maintain their percentage ownership of our ordinary shares by buying a proportional number of any new ordinary shares that we issue. However, Dutch law and our articles of association permit our shareholders to authorize our board to exclude or limit these preemptive rights. This authorization may not continue for more than five years but may be given on a rolling basis.
It is common practice for Dutch companies to seek to renew this authorization annually on a rolling basis. We currently have authorization from our shareholders to exclude or limit these preemptive rights until December 16th, 2022. The board unanimously recommends a vote for the proposal. The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page eight, as well as in other materials that uniQure has sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all the received voting instructions and pending certification of the vote, with 21,988,991 votes for, 16,902,050 votes against, and 16,293 votes abstained, the proposal is adopted.
The seventh proposal to be acted upon by the shareholders is the reauthorization of the board to acquire uniQure's own fully paid-up ordinary shares up to a maximum of 10% of the issued share capital of uniQure for a period of 18 months from the date of the 2022 annual meeting in open market purchases through privately negotiated transactions or by means of self-tender offer or offers at prices per share ranging up to 110% of the market price per share at the time of the transaction. The current authorization of our board to repurchase shares expires on December sixteenth, 2022. The board unanimously recommends a vote for the proposal.
The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page nine, as well as in other materials that uniQure sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all received voting instructions and pending certification of the vote, with 38,855,064 votes for, 35,445 votes against, and 16,825 votes abstained, the proposal is adopted.
The eighth proposal to be acted upon by the shareholders is the appointment of KPMG Accountants N.V. or KPMG, an independent registered public accounting firm, as the external auditor charged with, one, auditing the Dutch annual accounts to be prepared in accordance with the International Financial Reporting Standards as adopted by the European Union, IFRS. For the financial year ending December 31, 2022, and two, serving as our independent registered public accounting firm for purposes of reporting pursuant to U.S. law for the fiscal year ending December 31, 2022. As required by Dutch law, shareholder approval must be obtained for the selection of KPMG to serve as our auditor and independent registered public accounting firm. KPMG has served as our independent registered public accounting firm since June 2019.
The services provided to us by KPMG during the years ending December 31, 2020 and 2021 are described below under Principal Accountant Fees and Services. Representatives of KPMG are present at this meeting and can make a statement if they desire to do so. KPMG's report on the financial statements for the fiscal year ending December 31, 2021, which is the only such report issued for these financial statements, does not contain an adverse opinion or a disclaimer of opinion, and it was not qualified or modified as to uncertainty, audit scope, or accounting principles. The audit committee annually reviewed the independent registered public accounting firm's independence, including reviewing all relationships between the independent registered public accounting firm and us, and any disclosed relationships or services that may impact the objectivity and independence of the independent registered public accounting firm and the firm's performance.
We do not believe that any relationships exist which would interfere with KPMG's independence. The board unanimously recommends a vote for the proposal. The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page 10, as well as in other materials that uniQure has sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all received voting instructions and pending certification of the vote, with 38,876,039 votes for, 25,996 votes against, and 5,299 votes abstained, the proposal is adopted.
The final proposal to be acted upon by the shareholders is to approve on an advisory basis the compensation of the committee's named executive officers as disclosed in the proxy statement for the 2021 annual meeting pursuant to item 402 of Regulation S-K, including the compensation discussion and analysis, the 2021 summary compensation table, and other related tables and disclosure. The executive compensation program is designed to align compensation with our strategic imperatives, align the interest of management with the shareholders, and attract and retain talented executives. Please see the compensation discussion and analysis beginning on page 25 of the proxy statement for additional details, including information about the fiscal year 2021 compensation of our named executive officers.
We believe that the proposed compensation is consistent with the principles of our remuneration policy as presented earlier and has provided an important incentive for the achievement of uniQure's high performance over the past year. The board unanimously recommends a vote for the proposal. The board's statement in support of this proposal appears in uniQure's proxy statement beginning on page 12 and pages 25-40, as well as in other materials that uniQure sent to shareholders. We will now announce the results of the vote on the proposal.
In accordance with all received voting instructions and pending certification of the vote, with 30,883,737 votes for, 939,642 votes against, 13,034 votes abstained, and 7,070,921 non-cast votes, the proposal is adopted.
Voting has now been completed on all matters on the agenda, and no further business has been brought before this meeting. Following this meeting, the secretary will complete the count of the proxies, including examination of all proxies for validity, and we will report the final results of the voting. As there is no further business to come before this meeting, this meeting is concluded. I would like to thank you all for attending.
This concludes the meeting. You may now disconnect.