A Gene Therapy Study for Hemophilia B

Hemophilia B, or Christmas disease, is a genetic bleeding disorder resulting in the lack of
ability to produce blood-clotting factor IX (FIX). Individuals with hemophilia B suffer
repeated bleeding events, which can cause chronic joint disease and sometimes leads to death
due to the inability for blood to clot efficiently. This chronic joint disease can have
significant physical, psychosocial, and quality-of-life effects, including financial burden.
The current treatment is intravenous infusion of FIX protein products, either
prophylactically or in response to bleeding.

The approach being tested in this study uses a novel recombinant adeno-associated virus
(AAV), which in nature causes no disease, to deliver the human factor IX (hFIX) gene to the
liver cells where FIX is normally made. Recent data of a gene therapy study showed
preliminary encouraging results with the approach of using an AAV vector carrying the factor
IX gene. This study will seek to determine the safety and kinetics of a single IV infusion of
SPK-9001 (a novel AAV vector carrying a high specific activity factor IX variant).

Inclusion Criteria:

- Able to provide informed consent and comply with requirements of the study

- Males ≥18 y.o. with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous
factor IX)

- Received ≥50 exposure days to factor IX products

- A minimum average of 4 bleeding events per year requiring episodic treatment of factor
IX infusions or prophylactic factor IX infusions

- No measurable factor IX inhibitor as assessed by the central laboratory and have no
prior history of inhibitors to factor IX protein

- Agree to use reliable barrier contraception until 3 consecutive samples are negative
for vector sequences

Exclusion Criteria:

- Evidence of active hepatitis B or C

- Currently on antiviral therapy for hepatitis B or C

- Have significant underlying liver disease

- Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* subjects who
are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible
to enroll)

- Have detectable antibodies reactive with AAV-Spark100

- Participated in a gene transfer trial within the last 52 weeks or in a clinical trial
with an investigational drug within the last 12 weeks

- Unable or unwilling to comply with study assessments