Issue link: http://www.e-digitaleditions.com/i/637578
14 HD Insights, Vol. 13 HD INSIGHTS: Can you tell us how Roche became interested in Ionis Pharmaceuticals? SCHOBEL: Roche's strategy of innovation is to follow the science and disease areas in which we believe we can make the greatest difference in peoples' lives. We consider our collaboration with Ionis Pharmaceuticals in HD to be true to this strategy. The particular thing that attracted us is that Ionis has generated a huntingtin antisense oligonucleotide (ASO). This is a second- generation antisense therapy—the first to enter clinical development—designed to reduce the production of all forms of HTT, including mHTT. The life-transforming potential of this ASO made it a very attractive opportunity for us. HD INSIGHTS: HTT Rx recently began a clinical trial with a Phase I study in individuals with early HD. Can you tell us about that? SCHOBEL: First, I should say that Ionis is running the trial. They are in charge of development until the end of Phase I. In the Phase I trial, we are seeking to better understand the ASO. The two key parameters we are interested in are that it is safe and well tolerated, and whether its expected huntingtin-lowering action is proven through the lowering of protein levels in participants' cerebrospinal fluid (CSF). HD INSIGHTS: Can you tell us about measuring HTT levels in the CSF? The assay has not been widely used, and has never been used in a clinical trial. SCHOBEL: What is known is coming out of the collaboration with CHDI and the labs of Dr. Ed Wild and Dr. Amber Southwell. They have shown in clinic that one can measure mHTT in the CSF, which is a very exciting development. These assays appear to be ready for prime time. The other exciting aspect of the assays is that they track disease stage, and associate with clinical severity, at least in cross-section. We want to learn more about how those assays perform longitudinally in terms of their test- retest reliability. A forthcoming study – the HDClarity study – will hopefully elucidate that. In the Phase I study of HTT Rx , we are looking to see whether HTT Rx can change the levels of mHTT and total HTT in the CSF from baseline. That would be a very exciting first-in-human clinical accomplishment. Meet the Partner VITAL SIGNS NAME: Scott Schobel, MD, MS TITLE: Translational Medicine Leader, Hoffmann-La Roche Pharmaceuticals EDUCATION: BA, Japanese, University of Minnesota; MD, University of North Carolina-Chapel Hill; MS, Columbia University Mailman School of Public Health HOBBIES: Skiing; studying languages (currently German); chasing after his three sons Copyright © Huntington Study Group 2016. All rights reserved. H D I N S I G H T S Dr. Scott Schobel Dr. Scott Schobel, former Professor of Psychiatry at Columbia University School of Medicine, currently leads clinical efforts at Roche to develop Ionis Pharmaceuticals' IONIS-HTT Rx , the first huntingtin- lowering therapy being evaluated in humans. He took a few moments to share his thoughts with HD Insights on the compound, Roche, and the future of HD therapeutics. The following is an edited transcript of the conversation.