Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease

This was a Phase 2, open-label study in participants with Pompe disease, a lysosomal storage
disorder. Duvoglustat is designed to act as a pharmacological chaperone of alpha-glucosidase,
in order to restore enzyme activity. This study consisted of a 28-day screening period, an
11-week treatment period, and a 1-week follow-up period. Three dosing regimens of oral
duvoglustat were to be evaluated (Cohort 1: 2.5 g daily for 3 days, followed by no study drug
for 4 days; Cohort 2: 5 g daily for 3 days, followed by no study drug for 4 days; Cohort 3: 5
g daily for 7 days, followed by no study drug for 7 days).

Participants meeting all eligibility criteria underwent physical examination,
electrocardiogram, spirometry, muscular strength test, functional muscle test, 6-minute walk
test (when appropriate), laboratory tests, magnetic resonance imaging, and muscle (needle)
biopsy. Quality of life was assessed via the 36-Item Short Form Health Survey questionnaire.
Functional ability and level of handicap was assessed by Rotterdam handicap scale.

Inclusion Criteria:

- Male or female, 18 to 74 years of age inclusive

- Diagnosis of Pompe disease based on clinical assessment, enzyme assay, and/or
genotyping. Confirmatory genotyping will be performed on all participants who are
screened for the study

- Naïve to enzyme replacement therapy (ERT) or has not received ERT in the 3 months
prior to screening

- Willing not to initiate ERT or other prohibited treatment during study participation

- Functional grade for arms and/or legs ≥2 OR sitting forced vital capacity ≥30% and
<80% of predicted value, reproducible between screening and baseline (±15%)

- Participants of reproductive potential agree to use reliable methods of contraception
during the study

- Participant or legal representative is willing and able to provide written informed
consent

Exclusion Criteria:

- Any intercurrent condition that may preclude accurate interpretation of study data

- Obstructive pulmonary disease

- Invasive ventilatory support

- Use of noninvasive ventilatory support >8 hours/day while awake

- History of QTc prolongation >450 milliseconds (msec) for males and >470 msec for
females

- History of allergy or sensitivity to the study drug, including any prior serious
adverse reaction to iminosugars (such as miglustat or miglitol)

- Pregnancy or breast-feeding

- Current or recent drug or alcohol abuse

- Treatment with another investigational drug within 30 days of study start

- Use of prohibited medications ≤3 months prior to screening

- Otherwise unsuitable for the study in the opinion of the Investigator