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10-K
AVEXIS, INC. filed this Form 10-K on 02/28/2018
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Existing Treatments for SMA

The standard of care for patients with SMA Type 1 has traditionally been limited to palliative therapies, including life‑long respiratory care, ventilator support, nutritional care, orthopedic care and physical therapy. In December 2016, the FDA approved SPINRAZATM (nusinersen), developed by Biogen and Ionis Pharmaceuticals, Inc., for the treatment of SMA. Nusinersen employs an approach for the treatment of SMA called alternative splicing, which seeks to achieve more efficient production of full‑length SMN protein from the SMN2 gene. However, we believe that there is significant interest in a gene replacement therapy that can act on the underlying defect in the primary gene (SMN1) and can provide enhanced survival and motor function benefit via a one‑time dose.

Our Product Candidate: AVXS‑101 for the Treatment of SMA

AVXS‑101 is our proprietary gene therapy product candidate for the treatment of SMA. Because SMA is a neurodegenerative disease, reduced levels of SMN protein lead to continued degeneration. The goal of AVXS‑101 is to give patients a one‑time treatment to restore the body’s production of SMN protein to prevent further degeneration. Based on observations of our Phase 1 clinical trial, we believe that AVXS‑101 also enables increased motor function and enhances survival. AVXS‑101 contains the four elements that we believe are necessary for optimal delivery and function.

Components of AVXS‑101

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A recombinant AAV9 capsid shell:  a non‑integrating adeno‑associated virus 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, and into the spinal cord, thus allowing the option 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. In AVXS‑101, the DNA contained within the capsid shell is engineered to contain the other three critical elements of AVXS‑101, with the removal of the viral DNA, which leads to a significant reduction in pathogenicity and ability to replicate.

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A human SMN transgene:  a stable, functioning SMN gene that is introduced into the cell’s nucleus.

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Self‑complementary DNA technology:  the human SMN transgene is introduced as a self‑complementary double‑stranded molecule. The inclusion of this technology enables rapid onset of effect. Typically, a single‑stranded AAV vector must wait for cell‑mediated synthesis of its complementary DNA strand to form the double‑stranded DNA unit that is required for DNA replication and subsequent protein synthesis.

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