Uniqure Presents Hemophilia B Results

uniQure Announces Preliminary Topline Results from Low-Dose Cohort in Hemophilia B Phase I/II Gene Therapy Clinical Trial

--Meaningful Factor IX Expression Validates Successful Transduction of the Liver Using uniQure’s Proprietary AAV5 Vector--

--Four of Five Patients Have Fully Discontinued Prophylactic Recombinant Factor IX Therapy--

--Conference Call to Discuss Data Scheduled for 8:30 am EST Today, January 7--

Amsterdam, the Netherlands, January 7, 2016 —uniQure N.V. (Nasdaq: QURE), a leader in human gene therapy, today announced preliminary topline results from the low-dose cohort of an ongoing Phase I/II clinical trial being conducted in adult hemophilia B patients treated with uniQure’s novel AAV5/FIX gene therapy, AMT-060. All five patients in the low-dose cohort had Factor IX (FIX) phenotypic features of severe or moderately-severe hemophilia including documented Factor IX (FIX) levels less than 1-2% and required chronic treatment with prophylactic recombinant FIX (rFIX) therapy at the time of enrollment.
The first two patients out of five in the low dose cohort have completed at least 20 and 12 weeks of follow up and had central-lab-confirmed FIX expression levels of 5.5% and 4.5% of normal, respectively at the cutoff date of December 16^th, 2015.  The three additional patients have been dosed, but had not achieved the full 12 weeks of follow-up at the cutoff date. However, as of January 6, 2016, four of the five patients, including the first two patients enrolled in the study, have met a secondary objective in the trial by fully discontinuing prophylactic rFIX. The 12 week follow-up, post AMT-060 administration, marks the period in which investigators in the trial attempt discontinuation of prophylactic rFIX, based on FIX expression levels.  The first patient in the low-dose cohort experienced a mild, transient and asymptomatic elevation of transaminase levels at around 10 weeks post treatment.  This patient received a short, 8-week course of tapering prednisolone doses with rapid return of transaminase levels to baseline values. No elevated transaminase levels have been observed in the other four patients thus far, with all patients being on therapy for at least 10 weeks as of January 6, 2016.
AMT-060 consists of a codon-optimized wild type FIX gene and the LP1 liver promoter together with the AAV5 viral vector, manufactured using uniQure’s proprietary insect cell based manufacturing technology. AMT-060 is administered, without immunosuppressant therapy, through the peripheral vein in one treatment session for approximately 30 minutes. The study includes two cohorts, with the low-dose cohort using 5x10¹² gc/kg and the high-dose cohort using 2x10¹³ gc/kg. Thus far, there have been no patient screening failures due to pre-existing neutralizing antibodies against AAV5 and no patients have developed inhibitory FIX antibodies.
These early data from the low-dose cohort suggest that AMT-060 is generally well-tolerated and capable of successfully transducing the liver resulting in clinically meaningful FIX expression levels.  This current trial uses a starting dose of AAV5/FIX gene therapy that is similar to the highest dose of the same FIX gene cassette evaluated in a study conducted by Prof. Amit Nathwani and the St. Jude Children’s Hospital using an AAV8 serotype vector, and uniQure’s preliminary data are comparable with the endogenous FIX expression levels achieved in the St. Jude study. The results of the St. Jude study, which were published in the New England Journal of Medicine in 2011 and 2014, demonstrated that a durable mean FIX expression of 5.1% of normal (range 2.9% to 7.2%) can be achieved with this gene cassette and result in meaningful long-term clinical benefits for patients.  In the St. Jude study, four of six patients treated at the high dose had transient elevations of transaminase levels, managed with a tapering prednisolone regimen. The FIX gene cassette used in the St. Jude study is exclusively licensed by uniQure.
“Thus far, the overall tolerability and FIX expression profile in the low-dose cohort is encouraging for patients with hemophilia B and support the continuation of the study,” commented Professor Frank W.G. Leebeek, M.D. Ph.D. of the Erasmus Medical Center in Rotterdam, an investigator in the study. “Previous studies have demonstrated that maintaining durable FIX expression around 3% to 5% of normal may have a significant clinical benefit as measured by significant reduction in consumption of units of FIX concentrate and lower risk of spontaneous bleeding episodes.”
uniQure intends to present a more complete analysis of these data from this low-dose cohort at a scientific conference in the second quarter of 2016.  Subject to the Data Monitoring Committee’s approval, the Company also anticipates initiating enrollment of the high-dose cohort this quarter.
“These preliminary topline results support our hypothesis that AAV5/FIX can deliver clinically meaningful expression levels of FIX for patients with hemophilia B,” commented Dan Soland, Chief Executive Officer of uniQure. “So far, our AAV5-based gene therapies have been systemically administered to 13 adult patients across two clinical studies in two different disease states, and via direct central nervous system administration in four children in a third study, providing us with a strong safety dataset on the AAV5 vector and our proprietary insect cell based manufacturing technology.”
“Today, we are the only AAV gene therapy company in the world with both proprietary, commercial-scale manufacturing capabilities and encouraging clinical data across multiple diseases,” continued Mr. Soland.  “These preliminary results further support our modular platform approach and leadership in gene therapy.”