Phosphatase Inhibition by Intracoronary Gene Therapy in Subjects With Non-Ischemic NYHA Class III Heart Failure

Inclusion Criteria:

1. Subject must be age ≥18 years of age, at the time of signing the informed consent.

2. Chronic non-ischemic cardiomyopathy

3. 15% ≤ LVEF ≤ 35% by transthoracic echocardiography (TTE) at screening

4. 6MWT >50 meters

5. Medically stable, NYHA Class III HF for a minimum of 4 weeks while on appropriatemedical therapy (defined below) including, but not limited to:

6. Beta blocker therapy and ACE inhibitor or angiotensin receptor blocker (ARB) orsacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior toenrollment.May also receive aldosterone antagonist therapy. Doses of the above medicationsmust be stable for ≥ 30 days prior to enrollment; and

7. Cardiac resynchronization therapy (Zareba et al 2011), if clinically indicated,must have been implanted ≥ 90 days prior to enrollment. Internal cardioverterdefibrillator (ICD) must be implanted, if clinically indicated ≥ 30 days priorto enrollment.

8. Women of childbearing potential must use at least one of the following acceptablebirth control methods throughout the study and for 6 months after IP administration:

• Surgically sterile (bilateral tubal ligation, hysterectomy, bilateraloophorectomy) 6 months minimum prior to IP administration

• Intrauterine device in place for at least 90 days prior to receiving IP

• Barrier methods (diaphragm plus spermicide or condom) starting at least 30 daysprior to receiving IP

• Abstinence (the subject must be willing to remain abstinent from screening to 6months after receiving IP). Females are allowed to claim abstinence as theirmethod of contraception only when it is the preferred and usual lifestyle ofthe subject

• Surgical sterilization of the partner(s) (vasectomy) for >180 days prior to IPadministration

• Hormonal contraceptives starting > 90 days prior to IP. If hormonalcontraceptives are started less than 90 days prior to receiving IP, subjectsmust agree to use a barrier method (diaphragm plus spermicide or condom) fromscreening through 90 days after initiation of hormonal contraceptives

7. Males subjects capable of fathering a child:

• Must agree to use a condom and should also be advised of the benefit for afemale partner to use a highly effective method of contraception as a condommay break or leak when having sexual intercourse with a woman of childbearingpotential who is not currently pregnant from IP administration through 6 monthsafter the time of IP administration

• Must agree not to donate sperm for 6 months after time of receiving IP

• Documented evidence of vasectomy in males for 180 days minimum prior toreceiving IP is an acceptable form of contraception

• Males who claim abstinence as their method of contraception are allowed,provided they agree to use barrier methods should they become sexually activefrom screening through 6 months after receiving IP. Males are allowed to claimabstinence as their method of contraception only when it is the preferred andusual lifestyle of the subject

8. Appropriate candidate for protocol-specified intracoronary infusion in the judgmentof the infusing interventional cardiologist

Exclusion Criteria: Subjects are excluded from the study if any of the following criteria apply:

9. Chronic ischemic cardiomyopathy secondary to obstructive coronary artery disease

10. Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneouscardiac assist device therapy within 30 days prior to enrollment

11. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease,amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskineticLV aneurysm

12. Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior toscreening

13. Uncorrected Third degree heart block

14. Clinically significant myocardial infarction (MI) in the judgment of the subject'sphysician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months priorto enrollment

15. Prior heart transplantation, left ventricular reduction surgery (LVRS),cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device),surgically implanted LVAD or cardiac shunt

16. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reductionsurgery, heart transplant, conventional revascularization procedure, or valvularrepair within 3 months of IP dosing in judgement of investigator.

17. Known hypersensitivity to contrast dyes (not easily controlled by antihistamines)used for angiography; history of, or likely need for, high-dose steroid pretreatmentprior to contrast angiography.

18. Expected survival < 1 year in the judgment of the investigator

19. Active or suspected infection within 48 hours prior to intra-coronary infusion asevidenced by fever or positive culture

20. Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B orhepatitis C virus infection). If serology is positive and PCR is known to benegative, subject may be eligible (confirm with medical monitor).

21. Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) > 2x upper limit of normal (ULN) within 30 days priorto enrollment.

22. Chronic Kidney Disease Stage 5, dialysis dependent or eGFR<15 within 30 days priorto enrollment

23. Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μLwithin 30 days prior to enrollment

24. Anemia defined as hemoglobin <10 g/dL or transfusion dependent within 30 days priorto enrollment

25. Neutropenia defined as absolute neutrophils <1500 mm3 within 30 days prior toenrollment

26. Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency withan absolute neutrophil count <1000 cells/mm3

27. Previous participation in a study of gene transfer

28. Receiving investigational intervention or participating in another clinical studywithin 30 days of another investigational drug administration prior toadministration of AB-1002 that may impact the therapeutic potential of AB-1002.

29. Pregnancy or breastfeeding or plans to become pregnant within the next 12 months atthe time of screening

30. Subjects with any other condition which in the opinion of the investigator wouldpreclude participation in the study (including risk for non-compliance and anyintercurrent conditions that pose an undue medical hazard, or which could interferewith the interpretation of the study results)

31. Malignant neoplasm within 5 years of dosing, with the exception of those withnegligible risk of metastasis or death (such as adequately treated carcinoma insitus of the cervix, basal or squamous cell skin cancer, localized prostate canceror ductal carcinoma in situ)

32. Any documented history of non-compliance with medications, illicit drug use orlaboratory evidence of illicit drug use during screen period