Pipeline

EPI-743

EPI-743 is a drug candidate in clinical development primarily focused on inherited mitochondrial diseases. EPI-743 is administered orally, passes into the brain, and works by regulating key enzymes involved in the synthesis and regulation of energy metabolism.

Through expanded access protocols and prospective clinical trials, EPI-743 has been dosed for more than a cumulative 130,000 patient dosing days (as of November, 2013), and has recorded a favorable human safety profile. Subjects with over 15 discrete diseases have been treated.

EPI-589

EPI-589 is a drug candidate entering phase 1 clinical trials in healthy subjects in mid-Q3, 2013.

EPI-589 has completed non-clinical evaluation with a favorable safety and predictable pharmacologic profile.

Published Manuscripts

“α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging”, W. D. Shrader, A. Amagata, A. Barnes, G. M. Enns, A. Hinman, O. Jankowski, V. Kheifets, R. Komatsuzaki, E. Lee, P. Mollard, K. Murase, A. A. Sadun, M. Thoolen, K. Wesson and G. Miller,2011Bioorg. Med. Chem. Lett., 21(12), pp 3693-3698

“Initial experience in the treatment of inherited mitochondrial disease with EPI-743”, G. M. Enns, S. L. Kinsman, S. L. Perlman, K. M. Spicer, J. E. Abdenur, B. H. Cohen, A. Amagata, A. Barnes, V. Kheifets, W. D. Shrader, M. Thoolen, F. Blankenberg and G. Miller,2012Mol. Genet. Metab., 105(1), pp 91-102

“Towards a modern definition of vitamin E-evidence for a quinone hypothesis”, W. D. Shrader, A. Amagata, A. Barnes, A. Hinman, O. Jankowski, E. Lee, V. Kheifets, R. Komatsuzaki, P. Mollard, K. Murase, P. Rioux, K. Wesson and G. Miller,2012Bioorg. Med. Chem. Lett., 22(1), pp 391-395

“Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy”, A. A. Sadun, C. F. Chicani, F. N. Ross-Cisneros, P. Barboni, M. Thoolen, W. D. Shrader, K. Kubis, V. Carelli and G. Miller, 2012 Arch Neurol, 69(3), pp 331-338

“EPI-743: Preliminary report on Italian experience in open label study of three patients with acute Leber’s hereditary optic neuropathy” V. Carelli, P. Barboni, L. Caporali, A. Maresca, G. Miller, M. L. Valentino2012Mitochondrion 12(5), p 581.

“Improved redox status after liver transplantation in a patient with MMA mut0 subtype; functional evidence for EPI-743 therapy” A.-K. Niemi, T. Moore, T. Cowan, V. Kheifets, G. M. Enns 2012Mitochondrion 12(5), p 557.

“A0001 in Friedreich Ataxia: Biochemical Characterization and Effects in a Clinical Trial”, D. R. Lynch, S. M. Willi, R. B. Wilson, M. G. Cotticelli, K. Brigatti, E. C. Deutsch, O. Kucheruk, W. Shrader, P. Rioux, G. Miller, A. Hawi and T. Sciascia, 2012 Movement Disorders 27(8), pp 1026-1033.

“EPI-743 reverses the progression of the pediatric mitochondrial disease—Genetically defined Leigh Syndrome” D. Martinelli, M. Catteruccia, F. Piemonte, A. Pastore, G. Tozzi, C. Dionisi-Vici, G. Pontrelli, T. Corsetti , S. Livadiotti, V. Kheifets, A. Hinman, W. D. Shrader, M. Thoolen, M. B. Klein, E. Bertini, G. Miller, 2012 Molecular Genetics and Metabolism 107(3), pp 383-388.

“Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease” F. G. Blankenberg, S. L. Kinsman, B. H. Cohen, M. L. Goris, K. M. Spicer, S. L. Perlman, E. J. Krane, V. Kheifets, M. Thoolen, G. Miller and G. M. Enn, 2012 Molecular Genetics and Metabolism 107(4), pp 690-699.

“Glutathione: A redox signature in monitoring EPI-743 therapy in children with mitochondrial encephalomyopathies” A. Pastore, S. Petrillo, G. Tozzi, R. Carrozzo, D. Martinelli, C. Dionisi-Vici, G. Di Giovamberardino, F. Ceravolo, M. B. Klein, G. Miller, G. M. Enns, E. Bertini, F. Piemonte., 2013 Molecular Genetics and Metabolism 109(2), pp 208-214.

Published Conference Proceedings

“Rational Drug Development for Neuromuscular Disorders” Presented at 2014 Muscular Dystrophy Association Annual Meeting, Chicago, IL.

“CoQ10 analogues targeting mitochondrial impairment in Huntington’s disease”, W. D. Shrader, V. Kheifets, O. Jankowski, A. Barnes, A. Amagata and G. Miller, 2008 Journal of Neurology Neurosurgery and Psychiatry,79 (Supplement 1), pp A7-A7

“Clinical and radiological evidence for EPI-743 neuroprotection in mitochondrial disease”, F. Blankenberg, S. L. Perlman, S. L. Kinsman, K. M. Spicer, A. Barnes, V. Kheifets, W. D. Shrader, M. Thoolen, G. Miller and G. M. Enns, 2011 Annals of Neurology,70 (Supplement 15), pp S148-S148

“Preliminary Report on Initial Subjects Diagnosed With Genetically Confirmed Mitochondrial Disease at End-Of-Life Treated With EPI-743 Under FDA-Approved Expanded Access Protocol EPI-2009-1”, G. M. Enns, F. G. Blankenberg, S. DiMauro, M. Hirano, S. L. Kinsman, S. L. Perlman, D. Lynch, B. H. Cohen, R. P. Saneto, E. W. Hopkins, J. E. Abdenur, G. Miller, M. Thoolen and W. D. Shrader, 2011 Mitochondrial Medicine Conference, United Mitochondrial Disease Foundation, Bethesda, MD Chicago, Illinois, Special Session,

“EPI-A0001: New Potential Therapy for Friedreich Ataxia”, D. R. Lynch, S. M. Willi, R. B. Wilson, K. W. Brigatti, O. Kucheruck, E. C. Deutsch, W. D. Shrader, P. Rioux, G. Miller, A. Hawi and T. Sciascia, 2011 Annals of Neurology, 70 (Supplement 15), pp S86-S87

“EPI-743 alters the natural history of progression of Leber hereditary optic neuropathy”, A. A. Sadun, F. Chicani, F. N. Ross-Cisneros, M. Thoolen, G. Miller and V. Carelli, 2011, The American Ophthalmological Society, one hundred and fourty seventh annual meeting, Dana Point California, Abstract 9.

“EPI-743: Preliminary report on Italian experience in open label study of three patients with acute Leber’s hereditary optic neuropathy”, V. Carelli, P. Barboni, L. Caporali, A. Maresca, G. Miller and M. L. Valentino,2012Mitochondrial Medicine Conference, United Mitochondrial Disease Foundation, Bethesda, MD Abstract 85.

“EPI-743 reduces seizure frequency in RARS 2 defect syndrome” D Martinelli, M Catteruccia, M Klein, E Bevivino, M Thoolen, F Piemonte, A Pastore, G Tozzi, G Pontrelli, E Bertini, G Miller, C Dionisi-Vici. 12 International Congress of Inborn Errors of Metabolism, September 4, 2013, Barcelona Spain. Abstract O-029.