First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221

This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the
effect of a highly targeted rhGAA (ATB200) co-administered with a chaperone (AT2221).

The study aims to evaluate safety, tolerability, pharmacodynamics (PD), and immunogenicity of
ATB200 co-administered with AT2221. The study will be conducted in 3 stages.

In Stage 1, safety, tolerability, and PK will be evaluated following sequential single
ascending doses of intravenously infused ATB200.

In Stage 2, safety, tolerability, and PK will be evaluated following single- and
multiple-ascending dose combinations of ATB200 and AT2221.

In Stage 3, long term safety and efficacy will be assessed following 24 month treatment of
ATB200 co-administered with AT2221 (Miglustat)

In Stage 4, treatment period will begin at the end of Stage 3 and will continue as open label
extension until commercialization, study discontinuation or subject withdrawal, with
functional assessments every 6 months

No Muscle biopsies will be performed in this study.

Key Inclusion Criteria:

- Male and female subjects between 18 and 75years of age, inclusive

- Diagnosis of Pompe disease

Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

- Has received ERT with alglucosidase alfa for the previous 2-6 years, inclusive

- Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a frequency
of once every other week

- Must be able to walk 200-500 meters on the 6-Minute Walk Test (6MWT )

- Has upright Forced Vial Capacity (FVC) 30% to 80% of predicted normal value

ERT-experienced subjects (non-ambulatory):

- Has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for ≥2 years

- Is wheelchair-bound

ERT-naïve subjects (ambulatory):

- Must be able to walk 200-500 meters on the 6MWT

- Has upright FVC must be 30% to 80% of predicted normal value

- Subject has never received alglucosidase alfa

Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

- Has received ERT with alglucosidase alfa for >7years, inclusive

- Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a frequency
of once every other week

- Must be able to walk 200-500 meters on the 6-Minute Walk Test (6MWT )

- Has upright Forced Vial Capacity (FVC) 30% to 80% of predicted normal value

Exclusion Criteria:

- Subject has received treatment with prohibited medications within 30 days of Baseline
Visit

- Subject, if female, is pregnant or breastfeeding at screening

- Subject, whether male or female, planning to conceive a child during the study

- Subject has a medical or any other extenuating condition or circumstance that may, in
opinion of investigator, pose an undue safety risk to the subject or compromise
his/her ability to comply with protocol requirements

- Subject has a history of allergy or sensitivity to miglustat or other iminosugars

- Subjects with active systemic autoimmune disease such as lupus, scleroderma, or
rheumatoid arthritis. All subjects with autoimmune disease must be discussed with the
Amicus Medical Monitor

- Subjects with active bronchial asthma. All subjects with bronchial asthma must be
discussed with the Amicus Medical Monitor