Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B

Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting
Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a
proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX
with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding
episodes. This clinical program will test a gene transfer approach involving the use of a
gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate
the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable
plasma FIX activity between 10% and 40% of normal activity.

Inclusion Criteria:

- Males age 18-75 years, inclusive

- Established hemophilia B with ≥3 hemorrhages per year requiring treatment with
exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding
episodes

- Plasma FIX activity ≤2% (<1% for first cohort; then per protocol)

- Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody
negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic
acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative
(undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at
screening

Exclusion Criteria:

- Family history of inhibitor to FIX protein or personal laboratory evidence of having
developed inhibitors to FIX protein at any time (>0.6 Bethesda Units on any single
test)

- Documented prior allergic reaction to any FIX product

- Detectable AAV8 neutralizing antibodies

- Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or
more of the following:

- Platelet count <175,000/μL

- Albumin ≤3.5 g/dL

- Total bilirubin >1.5 x ULN and direct bilirubin ≥0.5 mg/dL

- Alkaline phosphatase >2.0 x ULN

- ALT or AST >2.0 x ULN (except for subjects who are HIV infected)

- Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging
of 2 or greater)

- History of ascites, varices, variceal hemorrhage or hepatic encephalopathy