Inclusion Criteria:

Participants must meet all inclusion criteria to be eligible for trial participation.

1. Males or females ≥ 50 years of age at the time of signing the informed consent.
2. Diagnosis of HFpEF as defined by European Society of Cardiology or American College of Cardiology/American Heart Association criteria
3. NYHA Functional Class II or III
4. LVEF ≥ 50% demonstrated by echocardiography (ECHO) performed at Screening with evidence of heart failure
5. Elevated NT-proBNP at Screening
6. NordicPRO-C6™ ≥ 11 ng/mL at Screening.
7. Stable dose of all concomitant HF medications for at least 4 weeks prior to Screening.
8. Body weight of at least 110 lbs (50 kg) and body mass index (BMI) within the range ≥ 18 to < 45 kg/m2.
9. Males must agree to the contraception requirements and females must be of non-childbearing potential
10. Able to understand and willing to sign a written informed consent form (ICF).
11. Willing and able to comply with trial procedures and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

1. Female trial participant who is pregnant or breastfeeding.
2. Known hypersensitivity to VS-041.
3. Cardiovascular disease other than HFpEF
4. Active intercurrent illness such as acute bacterial or viral infection.
5. History of illicit drug or alcohol abuse or addiction that in the opinion of the PI could affect participation.
6. Active chronic viral infection such as Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) at Screening.
7. Acute decompensated HF within 30 days of Screening
8. Lung disease within 12 months prior to Screening
9. History of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
10. History of any other condition including psychiatric disorders that, in the opinion of the PI, may preclude the participant from following and completing the protocol.
11. Have participated within the last 6 months in a clinical study involving an investigational product.
12. Any other reason which, in the opinion of the PI, would prevent the participant from participating in the trial.