Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure

72 subjects with ischemic cardiomyopathy. The Phase I portion (n=12 subjects) will be open
label. In the first cohort, six subjects will receive a single dose of 30 mg of JVS-100 with
a minimum of 3 days between each enrollment. After seven days following the enrollment of
the last patient of cohort 1, a safety assessment by the DSMC will be performed. Upon DSMC
approval, the second cohort of six subjects will receive a single dose of 45 mg of JVS-100
with a minimum of 3 days between each enrollment. After seven days following the enrollment
of the last patient of cohort 2, a safety assessment by the DSMC will be performed. Upon
DSMC approval, up to 60 subjects will be randomized (1:1:1) to receive a single dose of 30
mg or 45 mg of JVS-100 or matching placebo.

Inclusion Criteria:

- Willing and able to sign informed consent

- Greater than or equal to 18 years of age

- Poor quality of life as measured by the Minnesota Living with Heart Failure
Questionnaire (MLWHFQ)

- Impaired 6 Minute Walk test

- Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months

- Residual well-demarcated region of LV systolic dysfunction defined as at least 3
consecutive segments of abnormal wall motion by echocardiography read at the
echocardiography core laboratory

- LVEF less than or equal to 40% measured by echocardiography read at the
echocardiography core laboratory

- Subject receiving stable optimal pharmacological therapy defined as:

- ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose* for

- 30 days unless contraindicated

- Diuretic in subjects with evidence of fluid retention

- ASA unless contraindicated

- Statin unless contraindicated

- Aldosterone antagonist per physician discretion

- Subject must not have a permanent device placed in the coronary sinus at the time of
enrollment *As defined as no more than 50% change in dose

Exclusion Criteria:

- Planned revascularization within 30 days following enrollment

- Note: if an angiographic study has been performed within the last year and the
subject is enrolled, the angiography study report should be included as part of
the subject's file

- Estimated Glomerular Filtration Rate < 30 ml/min*

- Signs of acute heart failure within 24 hours of scheduled infusion

- History of aortic valve regurgitation classified as "moderate-severe" or worse

- Patients will be excluded who have:

- Known prior trauma to the coronary sinus

- In dwelling instrumentation that may hamper coronary venous catheterization,
including a biventricular pacing coronary sinus lead

- Mitral regurgitation defined as "severe" measured by echocardiography at the clinical
site

- Patients with planned mitral valve repair or replacement surgery

- Any patient with a history of cancer will be excluded unless:

- The cancer was limited to curable non-melanoma skin malignancies and/or

- The cancer was removed by a successful tumor resection, with or without
radiation or chemotherapy treatment, 5 years or more prior to enrollment in this
study without recurrence.

- Subjects with persistent (per ACC/AHA/EEC guidelines)53, defined as recurrent AF
episodes lasting longer than 7 days) or chronic atrial fibrillation will be excluded
unless:

- A stable, regular heart rate is maintained with a biventricular pacemaker

- A stable, regular heart rate is maintained with a univentricular pacemaker
pacing less than or equal to 40% of the time

- Inability to undergo 6 minute walk or treadmill exercise test

- Previous solid organ transplant

- Subjects with greater than 40% univentricular RV Pacing

- Subjects with uncontrolled diabetes defined as HbA1c >10 %

- Participation in an experimental clinical trial within 30 days prior to enrollment

- Life expectancy of less than 1 year

- Positive pregnancy test (serum βHCG) in women of childbearing potential and/or
unwillingness to use contraceptives or limit sexual activity as described in Section
8.2.1 below

- Unwillingness of men capable of fathering a child to agree to use barrier
contraception or limit sexual activity as described in Section 8.2.1 below

- Subjects who are breast feeding

- Subjects with a positive test results for hepatitis B/C and/or HIV will be excluded
unless:

- The subject is a carrier for hepatitis B/C but has never had an active flare

- Subjects with a history of Systemic Lupus Erythematosus (SLE) flare

- Total Serum Bilirubin >4.0 mg/dl

- Aspartate aminotransferase (AST) > 120 IU/L

- Alanine aminotransferase (ALT) > 135 IU/L

- Alkaline phosphatase (ALP): >300 IU/L

- Clinically significant elevations in PT or PTT relative to laboratory norms at day 0

- Critical limb ischemia that limits the patients from completing 6 minute walk or
treadmill testing

- Subjects with severe chronic obstructive pulmonary disease (COPD)

- Severe defined as having been hospitalized for COPD within the last 12 months

- Any subject requiring home oxygen use for treatment of the symptoms of COPD

- History of drug or alcohol abuse within the last year

- A subject will be excluded if he/she is unfit for the trial based on the discretion
of the site Principal Investigator