|AUDENTES THERAPEUTICS, INC. filed this Form 10-K on 03/13/2017|
University of Pennsylvania
Page 4 of 6
2016 Crigler-Najjar Work Plan
Deletions to original work plan are included and described below.
Additions to the original work plan for 2016 are described below as an ‘Additional Study, Expansion, Additional Requirement, or Additional Activity.
Crigler-Najjar (CN) syndrome is an autosomal recessive disorder of bilirubin metabolism that is caused by a variety of alterations in the coding sequence of the uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene. The total loss of UGT1A1 activity and the resulting severe jaundice and risk of neurological sequelae (kernicterus) are associated with CN type 1. Although several drugs can slightly reduce jaundice, most current medical management relies on phototherapy for at least 12 hours per day. However, phototherapy rapidly becomes less effective following puberty, increasing the risk for kernicterus, resulting in the need for liver transplantation to control the disease. The alternative, gene replacement therapy, is expected to be effective as CN syndrome is caused by the lack of a single gene product, UGT1A1. The continuous synthesis of UGT1A1 by the liver following systemic delivery of a gene therapy vector expressing UGT1A1 would be less risky than a liver transplant and potentially as effective.
Outlined below is our work plan for the evaluation of a candidate vector for the treatment for Crigler-Najjar syndrome, including studies to determination of efficacy in UGT1 KO mice. Following the selection of the clinical candidate vector, we will proceed to IND-enabling studies to allow for progression of this therapy into the clinic.
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