Gene Transfer Clinical Study in Crigler-Najjar Syndrome

This study will evaluate safety and preliminary efficacy of gene transfer in Crigler Najjar
Syndrome. Subjects will receive a single dose of AT342 delivered intravenously. A maximum of
3 dose levels of AT342 are planned for evaluation in this study. Up to four subjects will be
enrolled at each dose level including up to 1 subject at each dose level randomized to
control with delayed administration of the investigational product. Dose escalation to the
next dose level will be considered after evaluation of at least 4 weeks of data from subjects
dosed at the current dose level. One of the dose levels will be chosen for dose expansion,
and the chosen dose will be administered to all delayed-treatment control subjects.

The primary efficacy endpoint measure of change in total serum bilirubin will be assessed at
weeks 12 (whilst still on phototherapy) and week 18 (after phototherapy has been weaned)
after administration of AT342; and the primary efficacy endpoint measure of change in number
of hours of phototherapy will be assessed at week 18

This study will utilize an independent Data Monitoring Committee that will monitor subject
safety and provide recommendations to Audentes regarding dose escalation, dose expansion, and
safety matters.

Key Inclusion Criteria:

- Subject has a diagnosis of Crigler-Najjar syndrome resulting from a confirmed mutation
in the UGT1A1 gene as assessed by a Sponsor-approved testing facility.

- Subject is aged ≥1 year.

- Subject is prescribed daily phototherapy for a minimum of 6 hours within a 24-hour
period (daily illumination time).

Key Exclusion Criteria:

- Subject is currently participating in an interventional study or has received gene or
cell therapy.

- Subject has received a whole liver, partial liver, or hepatocyte transplant; or
subject has a liver transplant scheduled within the treatment period of this study.

- Subject has significant cholestatic disease at screening.

- Subject is receiving phenobarbital or other known inducer of UGT1A1 within 30 days of
screening.

- Subject tests positive for AAV8 neutralizing antibodies with titers above protocol
specified threshold.

- Other than as required per protocol, subject has received immune-modulating agents
within 3 months before dosing (use of inhaled corticosteroids to manage chronic
respiratory conditions is allowed); use of other concomitant medications to manage
chronic conditions must have been stable for at least 4 weeks before dosing.

- Subject has any clinically significant laboratory values, in the opinion of the
investigator.

- Subject has clinically significant underlying liver disease (other than CN) at
screening.

- Subject has a history of, or currently has, a clinically important condition other
than CN, in the opinion of the investigator.