TX000045-003 is a double-blind, randomized, parallel group, placebo-controlled, proof- of-concept (POC) study, evaluating 2 dose regimens of TX000045 over the course of a 24-week treatment period (the APEX study).

This study will enroll approximately 191 participants and eligible patients will be randomized to one of 3 treatment arms:

• Arm 1: Treatment Group 1: Placebo delivered subcutaneously (SC) every 2 weeks (Q2W) for 24 weeks
• Arm 2: Treatment Group 2: TX000045 SC at Dose A Q2W for 24 weeks
• Arm 3: Treatment Group 3: TX000045 SC at Dose B Q2W alternating with Placebo Q2W for 24 weeks

Inclusion Criteria:

1. Is a male or female of non-childbearing potential between the ages of 18 and 83 years.
2. Has a diagnosis of PH-HFpEF based on baseline echocardiogram and right heart catheterization (RHC).
3. Has NYHA functional class II- III heart failure.
4. Has 6MWT distance from 100 to 450m.
5. Chronic medication for heart failure or cardiovascular disease is at a stable dose prior to screening.
6. Is able to understand and provide documented consent for participation.

Exclusion Criteria:

1. Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.

2. Current or recent hospitalization prior to screening.

3. Recently received vasoactive drugs, pulmonary arterial hypertension-specific therapies, or a relaxin receptor agonist.

4. Initiated a new exercise program for cardiopulmonary rehabilitation or plans to initiate such a program during the study.

5. Has a body mass index <18 kg/meter square or >45 kg/ meter square.

6. Was previously administered TX000045, relaxin, or a relaxin fusion protein.

7. Historical or current evidence of a clinically significant disease or disorder such as significant lung disease, cardiovascular comorbitiies, liver disease, infectious disease, or malignancy.

8. Has any of the following clinical laboratory values during screening:

   1. Serum alanine aminotransferase or aspartate aminotransferase levels > 3 x the upper limit of normal (ULN) or total bilirubin > 3 x ULN;
   2. eGFR <30 mL/min/1.73 m2;
   3. HbA1c (glycosylated hemoglobin) >9%;
   4. Platelet count <50,000/millimeter cube;
   5. Hemoglobin <10.0g/dL;

9. History of hypersensitivity or reactions to drugs with a similar chemical structure or class to TX000045.

10. Is pregnant or breastfeeding.

11. Has a history of cancer within 5 years of screening other than basal cell carcinoma, cervical carcinoma, or squamous cell carcinomas of the skin.

12. Has a history of drug or alcohol abuse.

13. Was recently dosed in any clinical research study.