VAL-1221 Delivered Intravenously in Ambulatory and Ventilator-free Participants With Late-Onset Pompe Disease

The study will be conducted in two parts. Part 1 is a 3-month active control phase which
comprises 3 sequential cohorts of 4 participants each randomized to treatment with either
VAL-1221 (at 3, 10, or 30 milligrams/kilogram [mg/kg]) or positive control (recombinant human
acid alpha-glucosidase [rhGAA]). Eligible participants who complete Part 1, including those
maintained on rhGAA, will be offered inclusion in Part 2 of the study. Part 2 is a 9-month
uncontrolled extension to evaluate long-term effects of VAL-1221 given by intravenous (IV)
infusion once every other week at doses up to 30 mg/kg.

Inclusion Criteria:

- Participant is able and willing to provide informed consent prior to any study
procedures are performed

- Diagnosis of GSDII based on one of the following:

- Endogenous cultured skin fibroblast GAA activity less than (<) 40 percent (%) of
adult normal level

- Endogenous whole blood or dried blood spot GAA activity in deficiency range

- Genetic analysis showing pathogenic variants in both alleles

- Onset of Pompe disease-related symptoms after 1 year of age

- Previously treated with Myozyme or Lumizyme for at least 12 months and on a stable
regimen for the past 6 months

- Sexually active participants who are willing to use an acceptable method of
contraception (abstinence, oral contraceptives, barrier method with spermicide,
surgical sterilization, implanted or injectable contraceptives with a stable dose for
at least 1 month prior to Baseline, hormonal intra-uterine device [IUD] inserted at
least 1 month prior to Baseline) during the study and for 30 days after completion of
treatment

- If participant is female and not considered to be of childbearing potential, she
is at least 2 years post-menopause, has undergone a tubal ligation, a total
hysterectomy or bilateral oophorectomy

- If participant is female and of childbearing potential, she has a negative serum
pregnancy test during screening and Baseline and must be willing to undergo
pregnancy testing at specific intervals during the study

- Participant meets at least one of the following criteria: greater than (>) 30% and
<80% predicted upright forced volume capacity (FVC) or participant is able to walk
>20% but <80% predicted normal on 6-minute walk test with or without use of assistive
devices

- Able to comply with protocol requirements

Exclusion Criteria:

- Cardiac involvement in first year of life

- Anti-GAA antibody titers >1:51,200 at two time points

- Prior use of chaperone therapy for GSD-II within the last 12 months

- Use of immunosuppressive medication other than glucocorticoids within 6 months prior
to study enrollment

- Use of invasive ventilatory assistance other than Bilevel Positive Airway Pressure
(BiPAP) at night or during periods of rest

- Has received any investigational medication or has enrolled in any study involving
investigational drugs or therapies within 30 days prior to first dose of study drug

- Start of or change in usual regimen of albuterol or respiratory muscle training within
30 days prior to first dose of study drug

- History of sensitivity to any of the constituents of the study drug

- Participant is breastfeeding or planning to become pregnant or to breastfeed during
the study or is currently breastfeeding

- Participant has a medical condition or circumstance that, in the opinion of the
investigator, might compromise the participant's ability to comply with the protocol
or the participant's well-being or safety

- Participant has any condition that, in the view of the investigator, places the
participant at high risk of poor treatment compliance or of not completing the study