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AVEXIS, INC. filed this Form S-1/A on 02/01/2016
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standard of care for patients with SMA is limited to palliative therapies, including life-long respiratory care, ventilator support, nutritional care, orthopedic care and physical therapy.

Our Product Candidate — AVXS-101

          We believe gene therapy is a therapeutic approach that is well-suited for the treatment of SMA due to the monogenic nature of the disease, meaning it is caused by mutations in a single gene. AVXS-101 is our proprietary gene therapy product candidate for the treatment of SMA Type 1. AVXS-101 is designed to possess the key elements of an optimal gene therapy approach to SMA: delivery of a fully functional human SMN gene into target motor neuron cells; production of sufficient levels of SMN protein required to improve motor neuron function; and rapid onset of effect in addition to sustained SMN expression. AVXS-101 utilizes a non-replicating adeno-associated virus, or AAV, capsid to deliver a functional copy of a human SMN gene to the patient's own cells without modifying the existing DNA of the patient. Unlike many other capsids, the AAV9 capsid utilized in AVXS-101 crosses the blood-brain barrier, a tight protective barrier which regulates the passage of substances between the bloodstream and the brain, thus allowing for intravenous administration. In addition, AAV9 has been observed in preclinical studies to efficiently target motor neuron cells when delivered via either intrathecal or intravenous administration. AVXS-101 has a self-complementary DNA sequence that enables rapid onset of effect and a continuous promoter that is intended to allow for continuous and sustained SMN expression.

          We are currently developing AVXS-101 for the treatment of SMA Type 1 through intravenous administration. In April 2014, an open-label, dose-escalation Phase 1 clinical trial of AVXS-101 in patients with SMA Type 1 was initiated at Nationwide Children's Hospital in Columbus, Ohio, or NCH. The trial design allows for the enrollment of up to 15 patients across a maximum of three dosing cohorts. Key inclusion criteria include patients whose diagnosis of SMA Type 1 occurred before six months of age and have two copies of the SMN2 backup gene, as determined by genetic testing conducted by Clinical Laboratory Improvement Amendments of 1988, or CLIA, certified laboratories. Additionally, patients must have been no older than nine months of age (for the first nine patients) and six months of age (for the last six patients) at the time of vector infusion. 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.

          As of December 31, 2015, we had fully enrolled our Phase 1 trial, having dosed a total of 15 patients in the trial, divided into two dosing cohorts, and all 15 patients were event-free. 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 experienced either improvement or stabilization in motor skills 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, which has a maximum score of 64 points. 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 at or 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. Use of the term "proposed therapeutic dose" does not imply that we have established efficacy, but this dose is the


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