Table of Contents
that differs from the Hyperstack approach utilized by NCH, and utilizes globally compliant kanamycin-resistant genetic markers for plasmid selection. Our third party manufacturing partners
will also use this process. We intend to use product that we manufacture using this new process for future clinical studies, including our planned U.S. pivotal trial of AVXS-101 in SMA Type 1,
and, if AVXS-101 receives regulatory approval, to meet future commercial demand. We also intend to use AVXS-101 product that we manufacture for our planned Phase 1/2a clinical trial of AVXS-101
in SMA Type 2.
of the differences in these manufacturing processes, we are conducting a comprehensive comparability study to assess if the product that we manufacture is comparable to the
product used in the Phase 1 clinical trial. In conducting this study, we are performing various tests to evaluate key characteristics of the product manufactured by NCH for the Phase 1
trial, as well as the product that we are manufacturing at our own facility, and that our third party partners are manufacturing, using our new process. Among these analyses, we are conducting tests
to establish consistency with the dose concentration that was used in the second cohort of the Phase 1 trial, which is the dose that we are proposing to advance in our planned U.S. pivotal
trial of AVXS-101. Given the passage of time since NCH measured the dose concentration of the product used in the Phase 1 trial, our ability to demonstrate comparability in head-to-head testing
between the product used in the Phase 1 trial and the product manufactured using our new process may be complicated by any degradation or instability of the product manufactured by NCH.
in completing the comparability study to the satisfaction of the FDA could delay or preclude our development and commercialization plans and, thereby, increase the risk and time
to achieve regulatory approval of AVXS-101. We intend to provide the results of our comparability study, along with the full data from the Phase 1 clinical trial, in the data package that we
plan to review and discuss with the FDA at our end-of-Phase 1 meeting, which we expect to request in August 2017. If the results of the comparability study are not satisfactory, we may be
required to conduct additional
comparability work, modify our new process or conduct additional clinical trials of AVXS-101, any of which could adversely impact our ability to continue development, and obtain marketing approval, of
AVXS-101 for SMA Type 1, and our anticipated timelines for doing so, and have a material adverse effect on our business prospects.
Preclinical testing of our gene therapy product candidates for Rett syndrome and ALS may not result in our
advancement of these programs into clinical trials.
Although a substantial amount of our efforts to date have focused on the development of AVXS-101 for SMA, a key element of our strategy is to
discover, develop and potentially commercialize a portfolio of product candidates to treat other rare and life-threatening neurological genetic diseases. In furtherance of that strategy, we recently
announced that we had entered into a license agreement with REGENXBIO to develop and commercialize gene therapy treatments to treat two rare monogenic disorders: Rett syndrome and a genetic form of
amyotrophic lateral sclerosis, or ALS, caused by mutations in the superoxide dismutase 1, or SOD1, gene. Our development efforts for our Rett syndrome
and ALS programs are at an extremely early stage, and we have not yet completed IND-enabling preclinical studies for either of these programs. It is possible that future research and preclinical
development of these programs may not establish sufficient indications of clinical benefit or acceptable tolerability to support the submission of an IND for one or both of these programs, in which
case we may never initiate clinical trials, and we may be forced to suspend development activities for one or both of these programs. If we are not able to advance these programs into clinical trials,
we will not be able to commercialize products for these indications, which would have a material adverse effect on our future business prospects, financial condition and results of operations.