AAV2/8-LSPhGAA in Late-Onset Pompe Disease

This study will be a prospective, open-label trial designed to objectively assess the safety
and bioactivity of AAV2/8-LSPhGAA in subjects diagnosed with Pompe disease, which is caused
by a defect in acid α-glucosidase (GAA) gene. AAV2/8-LSPhGAA is intended to enable expression
of a functional copy of the GAA gene in subject's hepatocytes.

Inclusion Criteria:

- Diagnosis of Pompe disease by blood or skin fibroblast GAA assay and two pathogenic
variants in the GAA gene,

- Age: Greater than or equal to 18 years at enrollment.

- Subjects are capable of giving written informed consent.

- Able to walk at least 100 meters on the 6MWT (with assistive devices permitted).

- FVC within the range of 30% to less 90% (inclusive) of predicted in the upright
position.

- Receiving ERT for at least 104 weeks (inclusive) immediately preceding screening and
receiving a stable dose of ERT for the 52-week period immediately preceding dosing.

Females of childbearing potential must use at least one of the following acceptable birth
control methods throughout the study and for 6 months after dosing with ACTUS-101.

1. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6
months minimum prior to receiving ACTUS-101.

2. Intrauterine device in place for at least 90 days prior to receiving ACTUS-101.

3. Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior
to receiving ACTUS-101.

4. Abstinence (the subject must be willing to remain abstinent from screening to 6 months
after receiving ACTUS-101). Females are allowed to claim abstinence as their method of
contraception only when it is the preferred and usual lifestyle of the subject.

5. Surgical sterilization of partner(s) (vasectomy) for > 180 days prior toACTUS-101.

6. Hormonal contraceptives starting > 90 days prior to receiving ACTUS-101. If hormonal
contraceptives are started less than 90 days prior to receiving ACTUS-101, subjects
must agree to use a barrier method (diaphragm plus spermicide or condom) from
screening through 90 days after initiation of hormonal contraceptives

Male subjects:

1. Must agree to use a condom from Study Day 1 through 6 months after the time of
receiving ACTUS-101.

2. Must agree not to donate sperm for 6 months after the time of receiving ACTUS-101.

3. Documented evidence of vasectomy in males for 180 days minimum prior to receiving
ACTUS-101 is an acceptable form of contraception.

4. Males who claim abstinence as their method of contraception are allowed provided they
agree to use barrier methods should they become sexually active from screening through
6 months after receiving ACTUS-101. Males are allowed to claim abstinence as their
method of contraception only when it is the preferred and usual lifestyle of the
subject

Exclusion Criteria:

- ELISA positive for anti-AAV8 capsid IgG antibodies (>1:5).

- Invasive ventilation required or noninvasive ventilation required while awake and
upright.

- FVC <20% of predicted (supine).

- Invasive ventilation required or noninvasive ventilation required while awake and
upright.

- Clinically relevant illness within two weeks of enrollment including fever > 38.2o C,
vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative
to new therapy.

- Any condition that would interfere with participation in the study as determined by
the principal investigator.

- Received any live vaccination 4 months prior to study Day 1. (Subjects will also be
prohibited from receiving any vaccination within the 4-month period after study Day
1).

- Pregnant or nursing mothers.

- Anti-rhGAA IgG with sustained titer >1:12,800 for >6 months at time of enrollment.

- Serology consistent with exposure to HIV, or serology consistent with active hepatitis
A, B or C infection. Any active liver disease.

- GGT > 1.2x ULN adjusted for age and gender.

- Bilirubin > 1.2x ULN adjusted for age and gender (unless have a history of Dubin
Johnson syndrome).

- Active infection based upon clinical symptoms.

- Having started respiratory muscle strength training in the last 6 months prior to
study day 1 or having discontinued respiratory muscle strength training in the 6-month
period preceding study day 1, or having started respiratory strength training greater
than 6 months prior to study day 1 and unwilling to continue for the first year of
study participation.

- Received an investigational drug or participated in another interventional study
within 90 days of Study Day 1.