Safety and Efficacy of P-188 NF in DMD Patients

Based on a large number of studies conducted in pre-clinical models of muscular dystrophy and
heart failure, this study is being undertaken to explore the safety and efficacy of
Carmeseal-MD™ (P-188 NF) on endpoints associated with cardiovascular, pulmonary and
musculoskeletal function. These preclinical studies indicate that Carmeseal-MD™ acts to
stabilize fragile cell membranes thus maintaining cell function and preventing fibrosis,
necrosis and apoptosis in animal models of muscular dystrophy.

This is a single arm, open label trial that is designed to provide a first evaluation of
Carmeseal-MD™ in non-ambulatory patients with DMD. It assigns up to ten (10) patients to
receive a fixed dose of 5 mg of P-188 NF per Kg patient body weight (adjusted individually
for each patient at baseline visit) injected subcutaneously once-a-day for 52 weeks. The
first 3 enrolled subjects (Group 1) will be at least 18 years of age and up to 25 years of
age. Enrollment of Group 2 will begin after a review of Group 1 safety data through 28 days
of dosing of Carmeseal-MD™. Group 2 will include subjects that are at least 12 years of age
and up to 25 years old. Evaluations will be for Carmeseal-MD™ administered in addition to the
current standard of care therapies and interventions such as corticosteroids, ACE inhibitors,
ARBs, beta blockers, bronchodilator medications and airway clearance, cough assist and
non-invasive ventilation devices.

The major hypothesis for the trial is that measures of function of skeletal and cardiac
muscle that decline over the course of the disease will either remain stable or improve with
P-188 NF treatment when a decline would be expected. To assess these possible beneficial
effects, comparisons are planned between pre- and post-treatment on measures of function for
the various body systems affected by DMD.

Inclusion Criteria:

- Male

- 12 - 25 years of age

- Have phenotypic evidence of DMD

- Have documentation of the presence of a deletion, duplication or point mutation in the
dystrophin gene

- Willingness to receive daily subcutaneous (SC) injections of up to 3 mL

- Have LVEDV that is ≥100% of normal corrected for body mass when measured by cardiac
MRI

- Have impaired respiratory function (percent predicted PEF ≤80%)

- Have ability to perform PEF within 15% of first assessment

- Have mild to moderate fibrosis of the heart as assessed by MRI

- Have left ventricular ejection fraction fractions of <50%

- Have been non-ambulatory for at least six months

- Be on corticosteroids, with a stable treatment regimen for at least six months

- Have been on a stable treatment regimen for cardiac dysfunction for at least 3 months
prior to baseline (ACE inhibitors, beta blockers and/or ARBs)

- Have clinically acceptable screening values, including serum creatinine levels blood
urine nitrogen, cystatin C

- Have willingness and ability to comply with scheduled visits, drug administration,
drug administrative plan, study procedures, laboratory tests, and treatment
restrictions

- Be likely to survive for the duration of the treatment in the investigator's opinion

- Have ability to provide written informed consent (parent/guardian consent if
applicable)/assent (if <18 years of age).

Exclusion Criteria:

- Exposure to another investigational drug within 90 days prior to start of study
treatment

- Have DMD-related hypoventilation for which daytime assisted ventilation is needed

- Unable to perform pulmonary function testing

- Have respiratory failure

- Unable or unwilling to undergo scan with gadolinium as contrast agent

- Unable or unwilling to undergo echocardiography

- Have severe fibrosis of the heart as assessed by MRI

- Used carnitine, creatine, glutamine, oxatomide, coenzyme Q10 or vitamin E or any
herbal medicines with 30 days prior to baseline

- Have a history of major surgical procedure within 30 days prior to start of study
treatment

- Have ongoing immunosuppressive therapy (other than corticosteroids)

- Are participating in a therapeutic clinical trial

- Are on any concomitant medication with a depressive or stimulating effect on
respiration or the respiratory tract

- Have a diagnosis of chronic lung disease

- Chronic use of beta-2 agonists or any other bronchodilating medication (chronic use is
daily intake for more than 14 days within the last 6 months)

- Have moderate or severe hepatic impairment or moderate to severe renal impairment

- Have expectation of major surgical procedure during the conduct of the study

- Have prior or ongoing medical conditions that makes it unlikely that the course of
treatment or follow-up would be completed, or could impair the assessment of the
treatment results

- Have ever previously received P-188 NF as a therapeutic agent