HD Insights™

HD Insights A H u n t i n g t o n d i s e a s e r e s e a r c h Issue N o 7 -- Winter 2014 p e r i o d i c a l TM Copyright © Huntington Study Group 2014. All rights reserved. Meet the Company and its CEO Dr. Pratik Shah shares his hopes for Auspex Pharmaceuticals and their promising new tetrabenazine formulation. Pages 6, 7 Meet the Investigator Dr. Kathleen Clarence- Smith, a pioneer in HD research, discusses the past, present and future of HD pharmaceuticals.
 Page 2 HD Research in Canada Dr. Lise Munsie explores HD research throughout Canada. Page 11 PREDICTions Dr. Hans Johnson discusses high- performance computing in the PREDICT study. Page 8 HSG 2013: Highlights Dr. Christina Vaughan describes highlights of the 2013 HSG Meeting. Page 10 Prana Biotechnology released promising results from its phase 2 study of PBT2 in individuals with mild to moderate Huntington disease. In a randomized, double-blind, placebo-controlled study, 104 (95%) of 109 study participants completed the 26-week study on one of the three study arms – PBT2 250mg daily, PBT2 100mg daily, or placebo. Serious adverse events were more common in those on active drug (nine) than on placebo (one), but only one was deemed by site investigators to be related to study drug. In addition, on the principal secondary efficacy endpoints, Prana reported a statistically significant improvement on the Trail Making Test Part B, a test of executive function, in those randomized to PBT2 250mg. These results were similar to Prana's earlier phase 2 study in Alzheimer disease in which those randomized to PBT2 250mg had statistically significant improvements on both the Trail Making Test Part B and the Category Fluency Test. In the Huntington disease study, the improvement in executive function, which is impaired early in the disease, was also accompanied by a small, favorable signal in a key measure of functional capacity. No significant improvements were seen on other secondary efficacy measures in the study. A small (n=6) pilot imaging sub-study suggested reduced brain atrophy in those exposed to PBT2. PBT2 is a metal-protein attenuating compound that may affect metal mediated oligomerization of huntingtin. In the R2/6 mouse model of Huntington disease, daily oral administration of PBT2 improved motor performance of the mice, increased body and brain weight, and increased the lifespan of the mice by 26%. The phase 2 study was the first assessment of the drug in individuals with Huntington disease. Dr. Diana Rosas, an Associate Professor of Neurology at Harvard Medical School and the study's co-principal investigator, said, "I am very excited about (the study)… the drug is targeting a key pathological process that has been identified as significant in (HD) in both transgenic mouse models and in human disease, (and) in as little as six months, we were able to measure a potential clinical benefit and most importantly a potential slowing of progression… Finally, the addition of novel potential biomarkers, one of the first multi-center studies to do this, is also very exciting and provocative." In its press release on the study results, Prana indicated that it plans to advance PBT2 to a pivotal phase 3 clinical trial. Prana Releases Promising Results 1 Prana Biotechnology. Prana announces successful phase 2 results in Huntington disease trial. (press release) 2 Lannfelt L, Blennow K, Zetterberg H et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2008;7:779-86. 3 Cherny RA, Ayton S, Finkelstion DI et al. PBT2 reduces toxicity in a C. elegans model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the R6/2 mouse model of Huntington's disease. J Hunt Dis 2012;1:211-219. HD Insights, Vol. 7 1

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