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AUDENTES THERAPEUTICS, INC. filed this Form 10-K on 03/13/2017
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Clinical Development of AT342

The IND for AT342 is active, and we have initiated LUSTRO, a clinical assessment and Phase 1/2 run-in study designed to characterize the disease course, natural history, bilirubin variability and phototherapy usage of patients with Crigler-Najjar. We plan to report initial data from the LUSTRO study in mid-2017. We are also planning to initiate VALENS, the Phase 1/2 clinical study of AT342, in 2017, and to report preliminary data from VALENS in the fourth quarter of 2017.


LUSTRO - Clinical Assessment and Phase 1/2 Run-in Study (Ongoing): LUSTRO is an international, clinical assessment study of approximately 16 to 18 patients greater than or equal to one year of age with Crigler-Najjar. The primary objective of this study is to characterize the disease course, natural history, bilirubin variability and phototherapy usage of patients with Crigler-Najjar, with a specific focus on serum bilirubin levels and time on phototherapy. In addition, the study will assess the burden of disease on Crigler-Najjar subjects and caregivers. The study is also expected to identify patients for potential enrollment in VALENS, the Phase 1/2 study of Crigler-Najjar, and to serve as a within-patient control for VALENS.


VALENS - Phase 1/2 Study (Planned): The Phase 1/2 study of AT342 is a multicenter, multinational, open-label, ascending dose, delayed-treatment concurrent control study to evaluate the safety and preliminary efficacy of AT342 in approximately 12 Crigler-Najjar patients greater than or equal to one year of age. The study is expected to include nine AT342 treated subjects and three delayed-treatment concurrent control subjects.  Primary endpoints include safety (adverse events and certain laboratory measures, including immunological parameters) and efficacy (changes in serum bilirubin and number of hours on phototherapy).  Secondary endpoints include the proportion of subjects successfully weaned off of phototherapy, and UGT protein expression, DNA and RNA levels from liver biopsy at 24 weeks. Subjects are expected to remain on prescribed phototherapy for 12 weeks following administration of AT342.  Subjects with a meaningful decrease in bilirubin at week 12 will be tapered down and weaned off of phototherapy over a five week period, starting in week 13 and ending during week 17.  The primary efficacy analyses are expected to be conducted at the 12 and 18 week timepoints. Subjects are expected to be followed for a minimum of five years to assess long term safety and durability of effect.

Regulatory Interactions

The IND for AT342 is active, and we have conducted pre-CTA meetings with The Medicines and Healthcare Products Regulatory Agency (MHRA), the United Kingdom’s health authority, to discuss VALENS, the planned Phase 1/2 trial of AT342.  In addition, both the FDA and EMA have granted orphan drug designation for AT342.

AT982 for the Treatment of Pompe Disease

Overview of Pompe Disease

Pompe disease is a rare, severe, progressive, congenital neuromuscular disease. The overall incidence is estimated to be approximately one in 40,000 births although frequency and disease progression varies with age of onset, ethnicity and geography. The disease is characterized by mutations in the gene that encodes the enzyme acid alpha-glucosidase, or GAA. GAA is responsible for degrading glycogen within the lysosome, and dysfunction or absence of functional GAA results in toxic accumulation of glycogen in cells. Tissues and cells most affected by the disease are predominantly skeletal muscle, cardiac muscle and motoneurons.

The severity of Pompe disease symptoms and rate of progression is highly variable and correlated with age of symptom onset and the degree of enzyme deficiency. Infantile or early onset disease, the most severe form of Pompe disease, accounts for approximately one quarter of all affected patients. Those with early-onset disease are usually diagnosed in the first few months of life due to the severe presentation associated with total or near- total absence of GAA activity, and confirmatory diagnosis is made through genetic testing. These infants usually present with feeding difficulties, failure to thrive, hypotonia, progressive weakness, respiratory distress, severe enlargement of the tongue and thickening of the heart muscle. If left untreated, these children usually die in the first year of life. Those with late-onset disease typically have enzyme levels at 1% to 40% of normal and usually have symptoms such as reduced mobility and respiratory problems. Late-onset patients experience progressive difficulty walking