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uniQure Announces Long-Term Clinical Data from Ongoing Phase I/II Trial of AMT-060 and Confirms Dose for AMT-061 Pivotal Study in Hemophilia B

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Clinical Benefit of AMT-060 Maintained in All Patients Through up to Two and a Half Years of Follow-up

Second Dose Cohort Demonstrated a 93% Reduction in FIX Replacement Therapy Usage During Last Twelve Months of Observation, with Annualized Bleeds Near Zero

Dose Confirmed for Phase III Pivotal Study of AMT-061, with Patient Dosing Expected to Commence in First Quarter of 2019

uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced updated results from its ongoing Phase I/II trial of AMT-060, and provided an update on AMT-061, the Company’s next-generation gene therapy candidate currently in late-stage clinical development for patients with hemophilia B. AMT-060 is a first-generation gene therapy consisting of an AAV5 vector carrying a gene cassette with the wild-type FIX gene. The data on AMT-060 includes up to two and a half years of follow-up from the low-dose cohort and up to two years of follow-up from the second, higher-dose cohort. These clinical data were presented on Sunday, December 2 in a poster presentation at the 59th American Society of Hematology (ASH) Annual Meeting taking place in San Diego, California.

AMT-060 continues to be safe and well-tolerated, with no new serious adverse events and no development of inhibitors. All 10 patients sustained increases in FIX activity and improvements in their disease state as measured by reduced usage of FIX replacement therapy and decreased bleeding frequency.

All five patients in the second dose cohort of 2x1013 gc/kg continue to be free of routine prophylaxis at up to two years after treatment. During the last 12 months of observation, the mean annualized bleeding rate was 0.5 bleeds, representing an 88% reduction compared to the year prior to treatment. During the same period, the usage of FIX replacement therapy declined 93% compared to the year prior to treatment. Mean FIX activity increased from 7.1% in the first year after treatment to 8.3% in the second year and was 8.9% of normal at the last measurement.

"With up to two and a half years of follow-up, patients in the study continue to show evidence of durable clinical benefits, including sustained FIX activity, substantial reductions in the usage of replacement therapy and a near cessation of spontaneous bleeds," stated Professor Frank W.G. Leebeek, M.D. Ph.D. of the Erasmus University Medical Center in Rotterdam, the Netherlands. "Most importantly, since the last data update at ASH 2017, the study continues to demonstrate the long-term safety and tolerability of AAV5-based gene therapies, with no new treatment-related adverse events, no toxic cellular immune responses and no patients losing FIX activity.”

Advancing AMT-061 in Late-Stage Clinical Development
The Company recently announced initial clinical data in patients treated in a Phase IIb dose-confirmation study of AMT-061, a next-generation, AAV5-based gene therapy containing a patent protected FIX-Padua variant for the treatment of hemophilia B. Six weeks after administration, mean FIX activity for the three patients in the study was 31% of normal, and FIX levels continue to increase beyond the initial six to ten weeks of follow up. Based on the data obtained to date, no patient has required any infusions of FIX replacement therapy, reported any bleeding events or required any immunosuppression therapy.

The Data Monitoring Committee for the study has now reviewed these initial data and confirmed the dose of 2x1013 gc/kg for administration in the HOPE-B Phase III pivotal trial. The Company expects the dosing phase of the pivotal study to begin in the first quarter of 2019.

“The long-term data from our Phase I/II study of AMT-060 demonstrate the durability and safety of AAV5-based gene therapies and bode well for the late-stage development of AMT-061,” stated Matt Kapusta, chief executive officer of uniQure. “We believe AMT-061, which has clinically demonstrated the potential to provide functionally curative increases in FIX activity, may be a best-in-class gene therapy for patients with hemophilia B, and we look forward to treating our first patient in the pivotal study early next year.”

About AMT-060 and AMT-061
AMT-060 is a first-generation gene therapy consisting of an AAV5 vector carrying a gene cassette with the wild-type FIX gene. In October 2017, the Company announced the transition to AMT-061, which also consists of an AAV5 vector including the Padua variant of Factor IX (FIX-Padua). AMT-060 and AMT-061 are identical in structure apart from two nucleotide substitutions in the coding sequence for FIX. FIX-Padua has been reported in multiple preclinical and nonclinical studies to provide an approximately 8 to 9-fold increase in FIX activity compared to the wild-type FIX protein.

uniQure holds multiple issued patents in the United States, the European Union and Canada broadly covering methods of treating bleeding disorders, including hemophilia B, using AAV gene therapy with the FIX-Padua variant. Additional patents are pending in the United States and in the European Union.
AAV5-based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials, including four uniQure trials conducted in 25 patients in hemophilia B and other indications. No patient treated in clinical trials with the Company’s AAV5 gene therapies has experienced any reported cytotoxic T-cell-mediated immune response to the capsid.

About the Phase I/II study of AMT-060
The Phase I/II study is an open-label, multi-center study including 10 patients each receiving a one-time, 30-minute, intravenous administration of AMT-060, without the prophylactic use of corticosteroids. The study includes two dose cohorts of five patients each, with the first cohort receiving 5x1012 gc/kg and the second cohort receiving 2x1013 gc/kg. Nine patients in the trial were classified as having severe (