First-In-Human Study of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221

This study is an international, multi-center, study of Pompe disease patients that are currently receiving enzyme-replacement therapy (ERT). The purpose of this study is to find out if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.

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