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AVEXIS, INC. filed this Form 10-K on 02/28/2018
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Pre-Symptomatic SMA Types 1, 2, 3 (SPRINT): The planned multi-national trial is expected to enroll approximately 44 patients with two, three and four copies of SMN2 who are less than six weeks of age and who are pre-symptomatic at the time of gene therapy. The trial is designed to evaluate appropriate clinical endpoints, including developmental milestones, survival, bulbar function and safety, of a one-time IV infusion of AVXS-101. We expect to initiate the trial in the first half of 2018, and will provide more trial design details at the time of initiation.


Pediatric “All Comers” with SMA Types 1, 2, 3 (REACH): The planned multi-national trial is expected to enroll approximately 50 patients between approximately six months and 18 years of age who do not qualify for other AVXS-101 trials at the time of gene therapy. The trial is designed to evaluate a one-time IT dose of AVXS-101. We expect to initiate the trial late in the fourth quarter of 2018 or early 2019, and will provide more trial design details at the time of initiation.

In addition to our programs in SMA, we also intend to identify, acquire, develop and commercialize novel product candidates for the treatment of other rare and life‑threatening neurological genetic diseases that we believe can be treated with gene therapy. In June 2017, we announced that we had entered into an exclusive, worldwide license agreement with REGENXBIO for the development and commercialization of gene therapy using AAV9 to treat two rare neurological monogenic disorders: Rett syndrome and genetic ALS. We also licensed from NCH preclinical data suggesting promising safety and efficacy of gene therapy treatments for these disorders using AAV9, generated by our Chief Scientific Officer, Dr. Brian Kaspar.  See “—Our Collaboration and License Agreements—Strategic Collaborators and Relationships—Preclinical Programs for Rett Syndrome and Genetic ALS.” We expect to move forward with initiating IND-enabling studies in both Rett syndrome and genetic ALS and submit IND applications for both indications in late 2018 or early 2019. Current treatments for Rett syndrome and genetic ALS do not target the genetic cause of either disease, leaving what we believe to be a significant unmet need.

Rett Syndrome

Rett syndrome is a devastating, rare neurodevelopmental disorder characterized by slowed growth, loss of normal movement and coordination and loss of communication skills. Rett syndrome is an X-linked dominant genetic disorder caused by mutations in the gene for methyl-CpG-binding protein 2, or MECP2, which results in problems with the MECP2 protein, which is critical for normal brain development. Rett syndrome is very rare in males, but occurs in approximately one of every 10,000 female births in the United States with an estimated U.S. prevalence of approximately 8,500 based on applying natural history survival rates to historical births. Affected infants usually begin to show signs and symptoms between six and 18 months of age.  Current treatments for patients with Rett syndrome offer only symptomatic relief and do not target the genetic cause of the disease. 

Our Product Candidate: AVXS-201 for the Treatment of Rett Syndrome

We are conducting preclinical studies of AVXS-201, our proprietary gene therapy product candidate for the treatment of Rett syndrome. In completed preclinical studies using rodent models, it was observed that gene therapy to introduce re-expression of the MECP2 gene improved survival and improved the behavioral abnormalities associated with the disease model, including motor function.  AVXS-201, like AVXS-101, is composed of a recombinant AAV9 capsid shell, with a human transgene and a continuous promoter specifically designed for optimal MECP2 expression.

In a preclinical mouse model, we observed that certain doses of AVXS-201, delivered once into the CSF, increased the median lifespan of a Rett syndrome mouse model to over 200 days, compared to 66 days for untreated mice.  In a preclinical study of non-human primates, we observed that weight, blood parameters, and liver enzymes remained normal up to 18 months after a single lumbar intrathecal injection of AVXS-201.  We have observed no evidence of toxicity in wild-type mice treated with AVXS-201, and we observed no indications of tissue damage or disease in non-human primates post-injection. In both the preclinical mouse studies and preclinical non-human primate studies, we observed widespread targeting of AVXS-201 throughout the whole central nervous system after a single injection, as assessed by immunohistochemistry, immunocytochemistry, in situ hybridization and western blotting throughout various brain regions. 



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