A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease

This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal
storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is
designed to act as a pharmacological chaperone by selectively binding to misfolded
β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase
activity. The study consisted of a 21-day screening period, a 24-week treatment period, and
follow-up visit (Day 183, end-of-study). Participants were randomized in a 1:1 ratio to 1 of
2 treatment regimens for afegostat tartrate (3 days on treatment/4 days off or 7 days on
treatment/7 days off).

Inclusion Criteria:

- Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented
missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA)
alleles

- Clinically stable

- Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before
screening

- Willing to not initiate ERT or SRT treatment during study participation

- Male or female participants, 18 to 74 years old, inclusive

- At the screening period (Day -21 to Day -1), participants must have met at least 2 of
the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12
grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25
multiples of normal (MN), and spleen volume ≥2 MN

- All participants of reproductive potential were required to practice an acceptable
method of contraception

- Provided written informed consent to participate in the study

Exclusion Criteria:

- A clinically significant disease other than Gaucher disease, severe complications from
Gaucher disease, or serious intercurrent illness that precluded participation in the
study in the opinion of the investigator

- During the screening period, had any clinically significant findings as deemed by the
investigator

- Partial or total splenectomy

- Documentation of moderate or severe pulmonary hypertension, defined as pulmonary
arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related
lung disease

- History of allergy or sensitivity to the study drug or any excipients, including any
prior serious allergic reaction to iminosugars

- Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning

- Pregnant or breast-feeding

- Current/recent drug or alcohol abuse

- Treatment with any investigational product in the last 90 days before study entry

- Treatment in the previous 90 days with any drug known to have a well-defined potential
for toxicity to a major organ

- Presence of symptoms of gastrointestinal, liver or kidney disease, or other conditions
known to interfere with the absorption, distribution, metabolism, or excretion of
drugs