uniQure N.V 8-K, filed Dec 7, 2020
uniQure N.V. (QURE)
About this 8-K
uniQure N.V filed this 8-K on December 7, 2020, reporting on events of December 1, 2020.
Items reported
- Item 1.01: Entered into a material agreement
- Item 5.07: Shareholder vote results
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact Name of Registrant as Specified in Charter)
| The |
||||
| (State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| N/A | ||
| (Address of Principal Executive Offices) | (Zip Code) |
Registrant’s telephone number, including
area code:
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class: | Trading Symbol(s) | Name of each exchange on which registered: | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 1.01 Entry into a Material Definitive Agreement.
Collaboration and License Agreement
On December 1, 2020, uniQure biopharma BV, a wholly owned subsidiary of uniQure N.V. (the “Company”), entered into an amendment to its Collaboration and License Agreement with Bristol-Myers Squibb Company (“BMS”), dated April 6, 2015 (the “CLA”), pursuant to which the parties are collaborating to discover and develop gene therapy products for the treatment of cardiovascular and other diseases. Additionally, On December 1, 2020, the Company and E.R. Squibb and Sons, LLC, a subsidiary of BMS, entered into an amendment of the Master Clinical Supply Agreement, dated April 25, 2017 (the “Supply Agreement”, and together with the CLA, the “Collaboration Agreements”), for the supply of clinical gene therapy products pursuant to the CLA.
Summary of Original CLA
In May 2015, the Company entered into the now-amended CLA that provided BMS with exclusive access to the Company’s gene therapy technology platform for the research, development and commercialization of therapeutics aimed at multiple targets in cardiovascular and other diseases (“Collaboration Targets”). During the initial research term of the CLA, the Company supported BMS in discovery, non-clinical, analytical and process development efforts in respect of the Collaboration Targets. The initial four-year research term under the collaboration expired on May 21, 2019. In February 2019, BMS requested a one-year extension of the research term. In April 2019, following an assessment of the progress of this collaboration and the Company’s expanding proprietary programs, the Company notified BMS that the Company did not intend to agree to an extension of the research term but rather preferred to restructure or amend the collaboration to reduce or eliminate certain of the Company’s obligations under it.
The CLA as Amended
On December 1, 2020, BMS and the Company entered into an amendment to the CLA (the “Amendment”) reflecting the parties’ negotiations. Under the Amendment, BMS will be limited to the four Collaboration Targets that it previously designated (under the original CLA, BMS was entitled to designate up to ten Collaboration Targets), and the Company will continue to support the development of these four Collaboration Targets. Additionally, for a period of one-year from the effective date of the Amendment, BMS may replace up to two of these four Collaboration Targets with up to two new targets in the field of cardiovascular disease.
Under the Amendment, the research term has not been extended. However, for any Collaboration Targets that may be advanced, the Company will be responsible for manufacturing of research, clinical and commercial supplies using the Company’s vector technologies and industrial, proprietary insect-cell based manufacturing platform. BMS will reimburse the Company for its costs in support of the collaboration during the research, development, and clinical phases, and BMS will lead development, regulatory and commercial activities for any Collaboration Targets that may be advanced. The Company also has the obligation to provide access to its technology and know-how in the field of gene therapy to support up to four Collaboration Targets as may be designated pursuant to the terms of the Amendment and to support the collaboration through participating in a joint steering committee and other governing bodies. Subject to the terms of the CLA, BMS has the right to terminate the research, clinical and commercial supply relationships, and has certain remedies for failures of supply, up to and including technology transfer for any such failure that otherwise cannot be reasonably resolved. Both BMS and the Company may agree to a technology transfer of manufacturing capabilities pursuant to the terms of the CLA.
2
The Company has agreed to certain restrictions on its ability to work independently of the collaboration, either directly or indirectly through any affiliate or third party, on certain programs that would be competitive with a Collaboration Target. The Company has agreed to indication exclusivity for the current four Collaboration Targets. BMS may add or change the exclusive indications in the process of replacing Collaboration Targets as described above. The Company can opt out of the indication exclusivity by giving up certain economic rights under the CLA for each such indication that is affected by the Company opting out. If the Company opts out of an exclusive indication, the Company could pursue other targets for such indication other than a Collaboration Target.
Termination of Existing Warrants / Creation of a Change of Control Payment
Under the Amendment, the warrants that provided BMS with the ability in certain circumstances to acquire up to 19.9% of the Company are terminated. Instead, in the event of a change of control of the Company, BMS will receive a payment subject to certain limits to the amount paid to BMS.
Additional Agreement
The Company and BMS have simultaneously entered into a non-material Project Services Agreement for the purpose of the generating a library of AAV capsids for BMS’s use in the research and development of gene therapy applications. The activities under the Project Services Agreement will be conducted separately from the activities under the CLA.
The foregoing description of the terms of the Collaboration Agreements is not complete and is qualified in its entirety by reference to the text of those agreements, copies of which the Company intends to file as exhibits to its Annual Report on Form 10-K for the year ended December 31, 2020.
Item 5.07 Submission of Matters to a Vote of Security Holders.
The Company held its 2020 Extraordinary General Meeting of Shareholders (“EGM”) on Tuesday, December 1, 2020. The total number of the Company's ordinary shares (“Ordinary Shares”) eligible to vote at the EGM was 44,501,667, with one vote per Ordinary Share. The Company's shareholders voted on the following agenda item, which is described in more detail in the Company's proxy statement filed in connection with the EGM:
Agenda Item II - To appoint Dr. Robert Gut as a non-executive director
Regarding the proposal to appoint Dr. Robert Gut as a non-executive director of the Company's Board of Directors for a term ending at the Company's 2022 Annual General Meeting, 29,140,381 votes were cast in favor of the proposal, 153,755 votes were cast against the proposal, 14,054 votes abstained, and there were no non-votes and no uncast votes.
Item 8.01 Other Events.
On December 7, 2020, the Company issued a press release entitled “uniQure Announces Two-Year Follow-Up Data from the Phase IIb Study of Etranacogene Dezaparvovec and Long-Term Follow-Up Data for AMT-060 in Patients with Hemophilia B.” The full text of the press release is filed herewith as Exhibit 99.1 and is incorporated herein by reference.
3
Item 9.01 Financial Statements and Exhibits.
(d) The following exhibits are being filed herewith:
4
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| UNIQURE N.V. | ||
| Date: December 7, 2020 | By: | /S/ MATTHEW KAPUSTA |
| Matthew Kapusta | ||
| Chief Executive Officer and Chief Financial Officer | ||
5
Exhibit 99.1
uniQure Announces Two-Year Follow-Up Data from the Phase IIb Study of Etranacogene Dezaparvovec and Long-Term Follow-Up Data for AMT-060 in Patients with Hemophilia B
~ Sustained FIX Activity at Therapeutic Levels1 with a Mean of 44% of Normal at Two Years
After Administration of Etranacogene Dezaparvovec in Phase IIb Study ~
~ Long-term Clinical Benefit and Tolerability Maintained in All Patients
Through up to Five Years of Follow-Up in Phase I/II Study of AMT-060 ~
Lexington, MA and Amsterdam, the Netherlands, December 7, 2020 — uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced updated clinical data on the three patients treated in uniQure’s ongoing Phase IIb study of etranacogene dezaparvovec, an investigational AAV5-based gene therapy containing a patent-protected FIX-Padua variant for the treatment of patients with severe and moderately severe hemophilia B. These clinical data were presented today in an oral presentation at the virtual 62nd Annual Meeting of the American Society of Hematology (ASH). In addition, uniQure presented up to 5 years of follow-up data on the 10 patients in the Phase I/II trial of AMT-060, its first-generation gene therapy for the treatment of hemophilia B, in a poster presentation at the meeting. The oral presentation slides and poster are available in the Investor Relations section of uniQure's website at www.uniQure.com under Investor Downloads.
At Least Two Years of Stable, Therapeutic Levels of FIX Activity in Patients Treated with Etranacogene Dezaparvovec
The Phase IIb study of etranacogene dezaparvovec is an open-label, single-dose, single-arm, multi-center trial being conducted in the United States. Three patients with severe hemophilia (endogenous Factor IX (FIX) activity less than or equal to one percent) were enrolled in the study and received a single intravenous infusion of 2x1013 gc/kg. Prior to the administration of etranacogene dezaparvovec, all three patients showed low levels of pre-existing neutralizing antibodies to AAV5 but were not excluded from the trial on that basis. The patients in the Phase IIb study have now been followed for two years to assess FIX activity, bleeding rates and usage of FIX replacement therapy, and will be monitored for five years to evaluate the safety of etranacogene dezaparvovec.
In today’s oral presentation at ASH, two-year follow-up data show that all three patients have sustained FIX activity at therapeutic levels after the one-time administration of etranacogene dezaparvovec. Mean FIX activity for the three patients at two years after administration was 44.2% of normal (compared to 41% of normal at 52 weeks), with the first patient achieving FIX activity of 44.7% of normal, the second patient achieving FIX activity of 51.6% of normal and the third patient achieving FIX activity of 36.3% of normal. The second and third patients had previously screen-failed and were excluded from another gene therapy study due to pre-existing neutralizing antibodies to a different AAV vector. Reported FIX activity was measured using an activated partial thromboplastin time (aPTT) assay performed at a central laboratory.
1 Epidemiological data indicate that factor activity above 12% of normal is associated with substantial reduction or elimination of spontaneous bleeds and factor usage. Den Uijl IE et al Haemophilia 2011; 17(6):849-53
At two years after dosing, two of the three participants remain free from bleeds and use of FIX replacement therapy. A single bleed has been reported in one participant, who has used a total of two FIX infusions (excluding surgery). All patients have remained free of prophylaxis in the two years since receiving etranacogene dezaparvovec.
“These clinical data show that a single administration of etranacogene dezaparvovec continues to be well tolerated by these patients through two years of follow-up with the potential to achieve durable increases of FIX activity within the normal range,” stated Annette von Drygalski, M.D., PharmD, director of the Hemophilia and Thrombosis Treatment Center at the University of California San Diego and a principal investigator in the study. “The data offer encouraging support for the potential long-term benefits of etranacogene dezaparvovec, which are being further characterized in the ongoing Phase 3 HOPE-B study.”
“We are very pleased with these latest results demonstrating long-term clinical benefits of etranacogene dezaparvovec in these patients,” stated Ricardo Dolmetsch, president of research and development at uniQure. “These data will be included in regulatory submissions to the FDA and EMA, which we anticipate will begin in the second half of 2021, along with FIX activity and bleeding rates from the ongoing HOPE-B Phase III pivotal trial.”
Stable FIX Expression and Durable Reductions in Bleeding and FIX Consumption for up to 5 Years Following AMT-060 Gene Therapy
In the ongoing Phase I/II study of AMT-060, all 10 patients continue to show long-term clinical benefit, including sustained increases in FIX activity, reduced usage of FIX replacement therapy, and decreased bleeding frequency. At up to 5 years of follow-up, AMT-060 continues to be well-tolerated, with no new treatment-related adverse events since the last reported data and no development of inhibitors during the study. This represents the second-longest follow-up ever reported in a successful hemophilia gene therapy trial.
“In up to 5 years after a single administration, the Phase I/II study of AMT-060 has now demonstrated clear evidence of long-term clinical benefits in these patients, including sustained increases in FIX activity, improved disease phenotype and substantial reductions in bleeding,” stated Professor Frank W.G. Leebeek, M.D. Ph.D. of the Erasmus University Medical Center in Rotterdam, the Netherlands. “In addition, the AAV5-based AMT-060 continues to demonstrate positive long-term data in this trial that appear to be meaningful for the long-term outlook for hemophilia gene therapy and, in particular, etranacogene dezaparvovec.”
All five patients in the second dose cohort of 2x1013 gc/kg (the same dose being studied in the Phase III HOPE-B study of etranacogene dezaparvovec) continue to be free of routine FIX replacement therapy at four-and-a-half years after treatment. Based on the six months of data collected during the fifth year of follow-up, the mean annualized bleeding rate was zero compared to an average of 4 bleeds during the year prior to treatment, representing a 100% reduction. During this same period, the usage of FIX replacement therapy declined to zero compared to 354,800 IU in the year prior to treatment, representing a 100% reduction. Mean FIX activity over 4.5 years was 7.4%, while in the lower dose cohort, mean FIX activity was 5.2% over 5 years since treatment.
AMT-060 is uniQure’s first-generation gene therapy, consisting of an AAV5 vector carrying a gene cassette with the wild-type FIX gene. Data from this Phase I/II trial of AMT-060 also will be part of the regulatory submissions for marketing approval of etranacogene dezaparvovec.
About Etranacogene Dezaparvovec
Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). uniQure holds multiple issued patents in the United States and Canada broadly covering methods of treating bleeding disorders, including hemophilia B, using AAV gene therapy with the FIX-Padua variant. Etranacogene dezaparvovec has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration and access to Priority Medicine (PRIME) regulatory initiative by the European Medicines Agency. In June 2020, the Company and CSL Behring entered into a licensing agreement providing CSL Behring with exclusive global rights to etranacogene dezaparvovec. This licensing agreement is subject to antitrust regulatory review in the United States, Australia and the United Kingdom that is currently ongoing.
AAV5-based gene therapies have been demonstrated to be safe and well tolerated in a multitude of clinical trials, including being well tolerated in five uniQure trials conducted in nearly 80 patients in hemophilia B and other indications. No patient treated in clinical trials with the uniQure’s AAV5 gene therapies has experienced any confirmed cytotoxic T-cell-mediated immune response to the capsid. Additionally, pre-clinical and clinical data show that AAV5-based gene therapies may be viable treatments in patients with pre-existing antibodies to AAV5, thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates.
About uniQure
uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary gene therapies to treat patients with hemophilia B, Huntington's disease, Fabry disease, spinocerebellar ataxia Type 3 and other diseases. www.uniQure.com
uniQure Forward-Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. These forward-looking statements include, but are not limited to, whether clinical data from the HOPE-B Phase III pivotal trial will be included in regulatory submissions to the FDA and EMA in the second half of 2021 or ever, whether the clinical data proves to be meaningful for the long-term outlook for hemophilia gene therapy or etranacogene dezaparvovec, whether etranacogene dezaparvovec has the potential to lead to increases in FIX activity in the normal range and provide well-tolerated, long-term clinical benefits, whether AAV5-based gene therapies can provide clinical benefit to patients with pre-existing neutralizing antibodies, and whether we will obtain approval of our agreement with CSL Behring or otherwise close the transaction. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks associated with our and our collaborators’ clinical development activities, clinical results, collaboration arrangements, corporate reorganizations and strategic shifts, regulatory oversight, product commercialization and intellectual property claims, as well as the risks, uncertainties and other factors described under the heading "Risk Factors" in uniQure’s Quarterly Report on Form 10-Q filed on October 27, 2020. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.
uniQure Contacts:
| FOR INVESTORS: | FOR MEDIA: | |||
| Maria E. Cantor | Chiara Russo | Tom Malone | ||
| Direct: 339-970-7536 | Direct: 617-306-9137 | Direct: 339-970-7558 | ||
| Mobile: 617-680-9452 | Mobile: 617-306-9137 | Mobile:339-223-8541 | ||
| m.cantor@uniQure.com | c.russo@uniQure.com | t.malone@uniQure.com |