Study of Dapansutrile Capsules in Heart Failure

Inclusion Criteria:

1. Male and female subjects 18 years old or older

2. Symptomatic stable HF (NYHA class II-III) with reduced left ventricular ejectionfraction (LVEF≤40%, measured within 6 months of enrollment - no changes in cardiacmedications or new device implantation within past 2 months)

3. Peak exercise limited by shortness of breath and/or fatigue associated with arespiratory exchange ratio (RER) > 1.00 (reflecting maximal aerobic effort)

4. Reduced peak aerobic exercise capacity (peak VO2) to less than 80% of predicted valueby age/gender at Baseline

5. Plasma CRP or hsCRP levels > 2 mg/L at Screening

6. Acceptable overall medical condition to be safely enrolled in and to complete thestudy (with specific regard to cardiovascular, renal and hepatic conditions) in theopinion of the Principal Investigator

7. Ability to provide written, informed consent prior to initiation of any study-relatedprocedures, and ability, in the opinion of the Principal Investigator, to understandand comply with all the requirements of the study

Exclusion Criteria:

1. Women of childbearing potential, or men whose sexual partner(s) is a woman ofchildbearing potential who:

2. Are or intend to become pregnant (including use of fertility drugs) during thestudy

3. Are nursing

4. Are not using an acceptable, highly effective method of contraception until allfollow-up procedures are complete. (Acceptable, highly effective forms ofcontraception are defined as: oral contraception, intrauterine device, systemic [injectable or patch] contraception, double barrier methods, naturally orsurgically sterile, strict abstinence or partner has been sterilized. Ifhormonal-based birth control is being used, subject or subject's sexualpartner(s) must be on a stable-dose for ≥ 3 months prior to the Baseline visitand maintained at the same dosing level throughout the study.)

5. Abnormal blood pressure or heart rate response, angina or ECG changes (ischemia orarrhythmias) occurring during CPX

6. Presence or known history of autoimmune conditions (e.g., systemic lupuserythematosus, hypophysitis, etc.)

7. History or evidence of active tuberculosis (TB) infection at Baseline visit or one ofthe risk factors for tuberculosis such as but not limited or exclusive to:

8. History of any of the following: residence in a congregate setting (e.g., jail orprison, homeless shelter, or chronic care facility), substance abuse (e.g.,injection or non-injection), health-care workers with unprotected exposure tosubjects who are at high risk of TB or subjects with TB disease before theidentification and correct airborne precautions of the subject or

9. Close contact (i.e., share the same air space in a household or other enclosedenvironment for a prolonged period (days or weeks, not minutes or hours)) with aperson with active pulmonary TB disease within the last 12 months.

10. Use of any prohibited concomitant medications/therapies over the periods defined inSection 5.6.3 or planned use of any prohibited concomitant medications/therapiesduring the Treatment Period

11. Any other concomitant medical or psychiatric condition(s), disease(s) or priorsurgery(ies) that, in the opinion of the Principal Investigator, would impair thesubject from safely participating in the trial and/or completing protocolrequirements, including but not limited to:

12. physical inability to walk on a treadmill

13. decompensated HF (edema, NYHA IV)

14. significant ischemic heart disease, angina

15. arterial hypotension (blood pressure [BP] systolic < 90 mmHg)

16. arterial hypertension (resting BP systolic > 160 mmHg)

17. atrial fibrillation with rapid ventricular response

18. severe valvular disease

19. severe chronic obstructive or restrictive pulmonary disease

20. moderate-severe anemia (Hgb < 10 g/dL)

21. severe diabetic neuropathy or myopathy

22. Active or recent (within 2 weeks) infection prior to the Baseline visit

23. History of or known positive for HIV, Hepatitis B surface antigen or antibodies toHepatitis C Virus

24. Known history of renal impairment and/or creatinine clearance less than 50 mL/mincalculated by Cockcroft-Gault method

25. Active malignancy or recent malignancy with chemotherapy treatment within the past 6months

26. Enrollment in any trial and/or use of any investigational product or device within theimmediate 30-day period prior to the Baseline visit

27. Previous exposure to the investigational product