Study Assessing Left Ventricular Administration of a Genetic Medicine Directing Organ Regeneration in Heart Failure

Inclusion Criteria:

To participate, a subject MUST:

1. Be ≥ 18 and < 80 years of age;

2. Have medically stable heart failure of ischemic etiology, secondary to MI with NYHAclass II or III symptoms for at least 12 months before the initiation of screeningprocedures;

3. Have a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 40% by cMRI atscreening and baseline;

4. The subject is not a candidate for either percutaneous coronary intervention (PCI)or coronary artery bypass graft (CABG) surgery as determined by the principalinvestigator (or designee) in consultation with an interventional cardiologistduring the screening period;

5. Be on stable, outpatient, maximally tolerated guideline directed medical therapy (GDMT) for HF for 6 weeks, unless contraindicated, and remain stable during thescreening period;

6. Left ventricular (LV) end diastolic wall thickness of at least 8mm at the potentialmyocardial site for injection;

7. Be a candidate for cardiac catheterization;

8. Agree to protocol defined requirements for contraception;

9. Provide written informed consent.

Exclusion Criteria:

To participate, a subject MUST NOT HAVE:

1. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2)severe valvular (any valve) insufficiency/regurgitation within 12 months of consent;

2. Aortic stenosis with valve area ≤ 1.5cm2;

3. Prior heart transplant, history of LV reduction surgery, cardiomyoplasty, passiverestraint device

4. Had an acute myocardial infarction within the prior 30 days before initiation ofscreening;

5. Unstable angina pectoris within 30 days before initiation of screening procedures;

6. Idiopathic, valvular, peri/post-partum cardiomyopathy or other cardiomyopathy ofnon-ischemic etiology;

7. Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial constriction;amyloidosis; or uncorrected thyroid disease;

8. A history of ischemic or hemorrhagic stroke within 90 days of screening;

9. Liver dysfunction, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase)greater than 3 times upper limit of normal;

10. A baseline eGFR <35 mL/min/1.73m2;

11. Diabetes with poorly controlled blood glucose levels (HbA1c > 10%);

12. A hematologic abnormality during baseline testing;

13. Coagulopathy (INR > 1.5) not due to a reversible cause (e.g., warfarin and/or FactorXa inhibitors); Subjects who cannot be withdrawn from anticoagulation will beexcluded;

14. An underlying autoimmune disorder or current immunosuppressive therapy;

15. A contrast allergy that cannot adequately be managed by premedication;

16. Received cell-based therapy from any source;

17. Received any viral vector mediated gene therapy;

18. Evidence of active systemic infection at time of study product delivery;

19. HIV and/or active HBV, HCV or Covid-19 infection at screening or baseline;

20. Presence of LV thrombus;

21. Presence of a pacemaker or ICD generator with any of the followinglimitations/conditions:

22. manufactured before the year 2000

23. leads implanted < 6 weeks prior to screening

24. non-transvenous epicardial leads

25. subcutaneous ICDs

26. any other condition that, in the judgment of device-trained staff, would deeman MRI contraindicated;

27. A cardiac resynchronization therapy (CRT) device implanted < 3 months prior toconsent;

28. Other MRI contraindications

29. Mobitz II or higher degree atrioventricular block without a functioning pacemakerwithin 3 months of consent;

30. A history of drug abuse or alcohol abuse, or documented medical, occupational, orlegal problems arising from the use of alcohol or drugs within the past 24 months;

31. Cognitive or language barriers that prohibit obtaining informed consent or any studyelements;

32. Participation (currently or within the previous 30 days) in a cardiac relatedinvestigational therapeutic (including stem cell and gene-based therapies) or devicetrial;

33. Pregnancy, lactation, plans to become pregnant in the next 12 months, or isunwilling to use acceptable forms of birth control during study participation;

34. Expected survival < 1 year in the judgment of the investigator;

35. Active malignancy within the past 3 years (exceptions: localized prostate cancer,cervical or breast cancer in situ, or nonmelanoma skin cancer that has beendefinitively treated);