uniQure Reports Preclinical PoC for Gene Therapy Approach in Huntington's Disease

uniQure N.V. QURE, a leader in human gene therapy, today announced the publication of preclinical data supporting its proprietary Huntington's disease gene therapy program, AMT-130. Findings published in the current issue of the peer-reviewed journal Molecular Therapy-Nucleic Acids (www.nature.com/mtna/journal/v5/n3/index.html) provide preclinical proof of concept for uniQure's AMT-130 program and demonstrate the potential of a one-time administration of AAV5-delivered gene therapy into the central nervous system (CNS) to silence the Huntingtin gene (HTT). An inherited, mutated form of HTT causes Huntington's disease, a rare, fatal, neurodegenerative disorder that leads to severe physical and cognitive deterioration. The paper, titled "Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington's Disease", was authored by a research team led by Pavlina Konstantinova, Ph.D., Director of Emerging Technologies at uniQure under the direction of Chief Scientific Officer Harald Petry, Ph.D. The publication describes multiple approaches to silencing HTT using expression cassette-optimized artificial microRNAs (miHTTs). Several miHTT scaffolds were incorporated in an AAV5 vector using uniQure's established baculovirus-based manufacturing platform and administered to a humanized mouse model. The data demonstrate strong silencing of mutant HTT and total HTT silencing in vitro and in vivo. Furthermore, it was shown that HTT knock-down efficiency could be increased to 80% by using optimized miHTT scaffolds. The data published today were in part presented at the 11th Annual CHDI Huntington's Disease Therapeutics Conference on February 24, 2016 by Dr. Konstantinova. Based on these results, uniQure has initiated further studies of AMT-130 to support the filing of an investigative new drug application with the FDA. "Huntington's disease devastates families and there is currently no effective disease-modifying treatment," commented Charles W. Richard, M.D., Ph.D., Senior Vice President, Research and Development, Neuroscience at uniQure. "We are excited by the results of this study, and believe this degree of knock-down of mutant Huntingtin protein, if duplicated in our ongoing non-human primate safety toxicology studies and future human clinical trials, could significantly alter the course of the disease." "Dr. Konstantinova and her team have made significant progress in the search for an effective treatment for this cruel neurodegnerative disorder," said Dan Soland, Chief Executive Officer of uniQure. "AMT-130 now represents our third gene therapy product candidate in the CNS area, in addition to AMT-110 in Sanfilippo B and the NIH-sponsored program in Parkinson's disease. We will continue to leverage our deep experience in the CNS field, as well as our validated manufacturing capabilities and AAV5 technology, to advance AMT-130 towards the clinic."