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DNA sequence that enables rapid onset of effect and a continuous promoter that is intended to allow for continuous and sustained SMN expression.
April 2014, we initiated an open-label, dose-escalation Phase 1 clinical trial of AVXS-101 in patients with SMA Type 1 at Nationwide Children's Hospital in Columbus,
Ohio, or NCH. As of December 31, 2015, we fully enrolled our Phase 1 trial, having dosed a total of 15 patients in the trial. The trial design allows for the enrollment of up to 15
patients in a maximum of three dosing cohorts. The primary objective of the trial is safety and tolerability, while the secondary objective is to measure the time from birth until an "event," which is
defined as death or at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively. In September
2014, we completed the dosing of the first cohort of three patients, who received a dose of AVXS-101 administered at 6.7 × 1013 vector genome per kilogram, or
vg/kg, or the low dose, and as of December 31, 2015, we dosed 12 patients in the second cohort, who received the 2.0 × 1014 vg/kg dose or the proposed
therapeutic dose. Use of the term "proposed therapeutic dose" does not imply that we have established efficacy, but this dose is the dosing level that we presently intend to evaluate in future trials.
We will likely be required to conduct a pivotal trial followed by review and approval of the product candidate by the FDA before making any claims of efficacy as to our product candidate or the
appropriate dose. We did not enroll any patients in the third dosing cohort. Based on the preliminary results of the trial through December 31, 2015, no patient receiving AVXS-101 has
experienced an event. Of the 13 patients for whom data was available because they had at least one follow-up appointment as of December 31, 2015, all patients have experienced either
improvement or stabilization in motor function relative to their baseline measurement, as measured by The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, or CHOP INTEND, a
test developed to measure motor skills of patients with SMA Type 1. The Finkel 2014 Study showed an average decrease in CHOP INTEND scores in patients diagnosed with SMA Type 1. All
three patients in the first cohort, who received the low dose, and six of the 12 patients in the second cohort, who received the proposed therapeutic dose, have been on treatment for at least six
months as of December 31, 2015. Among these patients, the average improvement in CHOP INTEND scores after six months was 4.33 points for the low-dose cohort and 17.17 points for the proposed
therapeutic-dose cohort. Furthermore, increases in CHOP INTEND scores have been observed as early as one month after treatment and have been generally sustained above baseline through the period up to
December 31, 2015. Based on our observations to date, we believe that increases in CHOP INTEND motor assessments are dose-dependent. Although the results of the Finkel 2014 Study were not
pre-specified as a comparator for our trial, we believe the Finkel 2014 Study provides a useful context to consider the results to date of our trial. Based on preliminary results of the 15 patients
dosed as of December 31, 2015, we have observed AVXS-101 to be generally well-tolerated.
have an exclusive, worldwide license with NCH under certain patent applications related to both the intravenous and intrathecal delivery of AVXS-101 for the treatment of all types of
SMA, and an exclusive, worldwide license from a predecessor to REGENXBIO Inc., or REGENXBIO, under certain patents and patent applications owned by the Trustees of the University of
Pennsylvania and licensed to ReGenX, to use the AAV9 capsid for the in vivo gene therapy treatment of SMA in humans. In addition, we have a
non-exclusive, worldwide license agreement with Asklepios
BioPharmaceutical Inc., or AskBio, under certain patents and patent applications owned by the University of North Carolina and licensed to AskBio for the use of its self-complementary DNA
technology for the treatment of SMA.
was founded by John D. Harkey, Jr., our former Chairman, in 2010. Under Mr. Harkey's leadership, we formed a collaboration with NCH to explore the use of gene therapy for
the treatment of SMA and secured our first institutional investors and expanded our leadership team. Our current operations are a result of this collaboration with NCH and research conducted by our