As of July 23, 2015, there are three completed studies and multiple ongoing studies

being conducted with AAA. To date, approximately 890 adults have enrolled in early
development clinical trials with AAA with approximately 567 receiving single or
multiple doses of active drug. Dose levels used range from 0.1 mg/kg to 1.0 mg/kg as
i.v. infusions and 0.5 mg/kg s.c. injections.
The first-in-human study (ABC123456) was initiated in March 2008 and assessed
safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AAA in
cohorts of healthy adult volunteers. Since the start of the first study, numerous studies
have been undertaken to determine the safety and tolerability, PK and efficacy of
AAA in a variety of populations, including seven proof of concept (PoC) studies in
recovery from disuse, sporadic inclusion body myositis (sIBM), sarcopenia with
mobility limitations, and cachexia of cancer and chronic obstructive pulmonary
disease (COPD).
Study results to date indicate AAA has a good safety profile; is generally well
tolerated; has a predictable nonlinear kinetics caused by TMDD; and reliably
increases muscle volume and decreases limb adipose tissue within four weeks of
administration in both healthy volunteers and patients. Based on preclinical,
toxicology and clinical findings to date the benefit-risk profile remains positive and
provides evidence for continued development in patients with uncontrolled skeletal
muscle loss who would benefit from increased lean tissue.

 Definition of Severity of AE
The severity of the AE will be characterized as “mild, moderate or severe” according
to the following definitions:
• Mild events are usually transient and do not interfere with the subject’s daily
activities.
• Moderate events introduce a low level of inconvenience or concern to the
subject and may interfere with daily activities.
• Severe events interrupt the subject’s usual daily activity.