A Gene Transfer Study for Hemophilia A

Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a
mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII
protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the
joints, which can cause chronic joint disease and sometime results in death due to the
inability of the 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 (i.v.) injections of factor VIII protein products, either 2-3 times
weekly or in response to bleeding.

Recent preliminary clinical data of a hemophilia B gene transfer study (which is also being
conducted by Spark Therapeutics) shows all study participants achieving therapeutic factor IX
activity levels (average of maintaining factor IX activity levels around 30% of normal with
no confirmed bleeds, after receiving Spark gene transfer, with the approach of using the
novel bio-engineered recombinant adeno-associated viral (rAAV) vector carrying a high
specific activity of a factor IX gene. The approach being tested in this clinical research
study uses a further modified novel AAV vector (with a stronger attraction to the human
liver) to deliver the human factor VIII (hFVIII) gene into liver cells so that they can
produce factor VIII protein.

Inclusion Criteria:

- Males age18 years or older

- Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma
FVIII activity levels ≤ 2% of normal

- Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate

- Have experienced >10 bleeding events over the previous 12 months only if receiving
on-demand therapy and having FVIII baseline level 1-2% of normal

- Have no prior history of allergic reaction to any FVIII product

- Have no measurable inhibitor against Factor VIII as assessed by the central laboratory
and have no prior history of inhibitors to FVIII protein

- Agree to use reliable barrier contraception

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 (* participants
who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are
eligible to enroll)

- Have detectable antibodies reactive with AAV-Spark200 capsid

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