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LEXINGTON, MA, USA and AMSTERDAM, The Netherlands I August 15, 2024 I uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first patient has been dosed in a Phase I/IIa clinical trial of AMT-191 for the treatment of Fabry disease, a rare, inherited genetic disease. The Phase I/IIa study is a multi-center, open-label trial being conducted in the United States with two dose-escalating cohorts assessing the safety, tolerability and early signs of efficacy of AMT-191 in individuals with Fabry disease. “We are very pleased to begin patient dosing for AMT-191 in Fabry disease, marking a significant milestone in this year’s goal to advance three new gene therapy candidates into clinical studies,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure . “AMT-191 utilizes the same AAV delivery technology incorporated in HEMGENIX ® , which has an extensive, long-term safety profile and demonstrated effectiveness in patients with preexisting neutralizing antibodies to the AAV capsid. Our trial is designed to capture well-established endpoints in Fabry disease and to rapidly generate clinical proof-of-concept data for AMT-191 with a differentiated product profile relative to other Fabry programs in clinical development.” AMT-191 is an investigational AAV5-based gene therapy that uses a proprietary, highly potent promoter to deliver a galactosidase alpha (GLA) transgene designed to target the liver to produce GLA protein. In patients with Fabry disease, a pathogenic variant in the GLA gene leads to α-galactosidase A (aGAL-A) enzyme deficiency, which in turn results in a progressive accumulation of lipids in multiple cell types, including kidney and heart cells, eventually resulting in a multi-system disorder. AMT-191 may offer a novel potential one-time intravenously administered approach to treating Fabry disease. The Phase I/IIa clinical trial of AMT-191 will be conducted in the United States. The multicenter, open-label trial consists of two cohorts with up to six adult male patients each: a low-dose cohort of 6×10 13 gc/kg and a high-dose cohort of 3×10 14 gc/kg delivered through a one-time intravenous infusion. Patients will continue to receive their regular enzyme replacement therapy until the criteria for withdrawal is met and will be followed for a period of 24 months. The trial will explore the safety, tolerability, and early signs of efficacy by measuring the expression of lysosomal enzyme aGLA-A. Additional details are available on www.clinicaltrials.gov (NCT06270316). “This achievement marks an exciting period for the company as we advance additional programs into clinical trials this year,” stated Matt Kapusta, chief executive officer of uniQure . “Building on our momentum, we are focused on multiple, exciting catalysts across our pipeline, including engaging with the FDA to pursue an expedited clinical pathway for AMT-130 in Huntington’s disease and the initiation of new clinical studies in temporal lobe epilepsy and SOD1-ALS. With a strong balance sheet and runway extended through the end of 2027 from multiple cost reduction initiatives, we believe we are in an excellent position to execute on key value-creating milestones.” About Fabry Disease Fabry disease is an Xlinked- genetic disorder resulting from a deficiency of GLA. Based on a 2020 study published in the Journal of Therapeutics and Clinical Risk Management, the prevalence is estimated to be between one in 40,000 and one in 117,000 individuals. The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment with limited effectiveness in many patients due to poor cross-correction, with inefficient clearance of substrates in the target organs, in particular the kidney and the heart. About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington’s disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. www.uniQure.com SOURCE: uniQure

Dive Brief:BioMarin Pharmaceutical on Monday said it will limit sales of its hemophilia gene therapy Roctavian to the U.S., Germany and Italy in a bid to reach profitability with the slow-selling blood disease medicine.BioMarin will also pause production at a Roctavian manufacturing site and stop enrolling new patients in clinical testing of the therapy, which won approval in Europe in 2022 and the U.S. last year. The company expects its changes to lower direct Roctavian expenses to $60 million a year by 2025, by the end of which it anticipates the business will be profitable.While Roctavian was once viewed by analysts as a future blockbuster, demand for the one-time treatment has been scant, reflecting doubts about the durability of benefits it offers and a price tag thats hampered reimbursement discussions in the U.S. and Europe. Five patients received treatment between April and June, resulting in revenue of $7 million, BioMarin said Monday.Dive Insight:Roctavians commercial future has been in the balance as BioMarin and new company CEO Alexander Hardy weighed the therapys slow uptake.In April, Hardy laid out three options BioMarin was considering: staying the course on evidence sales were ramping quickly, reducing spending to ensure a reasonable return on investment, or selling Roctavian altogether.With the new plan disclosed Monday, BioMarin is choosing the middle ground and hoping it can increase sales by enough to match a lower level of expenses.This decision on Roctavian was based on four conclusions: One, our belief in the therapeutic profile of Roctavian and its role in hemophilia A; second, our understanding that a launch like this takes time; third, signs of progress in the United States, Germany and Italy; and lastly, a revised expense profile that gives us confidence Roctavian will contribute to profitability, Hardy told investors on a conference call late Monday afternoon.Hardy said he expects the pace of treatment in the U.S. to improve as more centers gain experience with Roctavian, which delivers a functional copy of the gene that people with hemophilia A lack. In Germany, the company is working to secure reimbursement following an agreement with the countrys health authorities on pricing, while in Italy Hardy reported signs of patient demand.Two of the five patients treated in the second quarter were located in Italy; the other three were in the U.S.BioMarin declined to give specific patient or revenue guidance Monday, although the company would likely need to treat several dozen patients to break even on $60 million in expenses. The list price for Roctavian in the U.S. is $2.9 million, while in Germany BioMarin agreed to a price that equates to about $900,000 in per-patient revenue.BioMarin also didnt detail what it plans to do with Roctavian rights in countries other than the U.S., Italy and Germany. In its statement, the company indicated that expansion into other markets will depend on progress in the three its chosen.BioMarins pared-down vision for Roctavian contrasts with the high potential the company and many outside it ascribed to hemophilia gene therapy. Long a goal for the gene therapy field, treatments like Roctavian promise to control bleeding for many years, freeing people with the disorder from regular infusions of so-called factor replacement therapy.But the arrival of newer and longer-lasting drugs like Roches Hemlibra and Sanofis Altuviiio have given patients new options, possibly lessening the appeal of gene therapy. Sales of Hemgenix, a gene therapy for the less common B form of hemophilia, have also been slow.Roctavians sluggish sales have put the focus more squarely on another new BioMarin drug, Voxzogo, thats approved to treatment a form of dwarfism. According to the company, roughly 3,500 children were on the drug at the end of the second quarter, and it is now BioMarins top-selling product. '