A Study of ROC-101 in Patients With Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated With Interstitial Lung Disease (ILD-PH) (ROCSTAR STUDY)

Key Inclusion Criteria:

1. Must be age 18 or older at the time of signing the informed consent form (ICF). Theparticipant must understand and voluntarily sign an ICF prior to any study-relatedprocedures

2. Documented findings on a right heart catheterization (RHC) consistent with adiagnosis World Health Organization (WHO) Group 1 PAH or WHO GROUP 3 PAH

3. Symptomatic Pulmonary Hypertension (PH) classified as WHO Functional Class II or IIIsymptoms

4. PAH participants: Pulmonary Vascular Resistance (PVR) of ≥ 5 Wood units, PulmonaryCapillary Wedge Pressure (PCWP) ≤ 15 mmHg and Mean Pulmonary Arterial Pressure (mPAP) > 20 mm Hg and ILD-PH participants: PVR of ≥ 3 Wood units, PCWP ≤ 15 mmHg andmPAP > 20 mm Hg

5. Participants on stable background therapy for PAH or ILD-PH.

6. Females of childbearing potential (as defined in protocol) must agree to use highlyeffective contraception (as defined in the protocol)

7. Male participants must follow protocol-specified contraception guidance.

8. Participants must be able to communicate well with Investigators, understand thestudy procedures in the ICF and are agreeable to complete the study in accordancewith the protocol.

9. Must be able to swallow tablets.

10. Pulmonary function tests (PFT): PAH participants at Screening as follows:

11. Forced Vital Capacity (FVC) > 70% predicted; or if between 60% to 70%predicted, or if not possible to be determined, confirmatory High-ResolutionComputed Tomography (HRCT) indicating no more than mild (<10% fibrosis) ILD;and

12. The ratio of FEV1 (first second)/FVC > 0.70 of predicted. ILD-PH participants at Screening as follows:

13. PFTs consistent with their ILD diagnosis and showing FEV1/ FVC ratio > 65% andHRCT > 10% fibrosis, based on the proportion of lung parenchyma affected byfibrotic changes.and,

14. Minimum FVC of 50% and diffusing capacity for carbon monoxide (DLCO) (correctedfor Hb g/dl) >25%

15. In PAH participants, i.e., Cohorts 1 and 2 only, ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram [CTPA] or pulmonaryangiography result), any time prior to Screening or conducted during the ScreeningPeriod, with a normal or low probability result that is not clinically significant

16. Acceptable Electrocardiogram (ECG) findings as assessed by the Investigator orqualified designee at the Screening Visit and at the Baseline Visit (Day 1),including each criterion as listed below:

• Normal sinus rhythm (HR) between 40 and 100 beats per minute, inclusive);

• Corrected QT Interval (QTcF) interval ≤ 450 msec (males) and ≤ 460 msec (females);

• QRS interval ≤ 120 msec; if > 120 msec, result will be confirmed by a manualover read

13. Body weight at the Screening visit and at Baseline (Day 1) is greater than 50.0 kgand the body mass index (BMI) is in the range of 19.00 to 36.00 kg/m2, inclusive

14. 6MWD ≥ 100 and ≤ 550 meters repeated twice, once during Screening Period and once atthe Baseline Visit (Day 1) and both values within 15% of each other, allowing for athird repeat if > 15% difference, calculated from the higher/highest value

Key Exclusion Criteria:

1. Diagnosis of PH WHO Groups 2, 4, or 5

2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension,schistosomiasis-associated PAH and pulmonary veno-occlusive disease and/or pulmonarycapillary hemangiomatosis

3. Positive blood test for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCVAb) (unless participants have had treatment for HCV and have anegative HCV ribonucleic acid [RNA] polymerase chain reaction [PCR]) or HIV antibody

4. Participants with known hypersensitivity to ROC-101 or any components of itsformulations

5. History of malignancy within the last 5 years, with the exception of fully excisedor treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cellcarcinomas of the skin

6. History of clinically significant (as determined by the Investigator) non-PAHrelated cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic,pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or otherdiseases that may limit participation in the study

7. Participation in another clinical trial involving intervention with anotherinvestigational drug, approved therapy for investigational use, or investigationaldevice within 4 weeks prior to Baseline Visit (unless it is in the follow-up periodof an interventional study), or if the half-life of the previous product is known,within 5× the half-life prior to Baseline Visit (Day 1), whichever is longer

8. Major surgery within 8 weeks prior to Baseline Visit (Day 1) or major surgeryscheduled or planned in the main study. Participants must have completely recoveredfrom any previous surgery prior to the Screening Visit

9. Prior heart or heart-lung transplants, or a participant listed for heart and/or lungtransplantation or prior pneumonectomy

10. Pregnant or breastfeeding females

11. Males who do not agree to protocol contraception guidelines

12. Uncontrolled systemic hypertension as evidenced by sitting SBP > 160 mm Hg orsitting diastolic BP > 100 mm Hg during Screening Visit and Baseline Visit (Day 1)after a period of rest

13. Systolic BP < 90 mm Hg during Screening Visit or at Baseline Visit (Day 1)

14. History of known pericardial constriction or a clinically significant (more thantrace or trivial [i.e., ≥10 mm]) pericardial effusion seen in diastole or in bothsystole and diastole on echocardiogram (ECHO) historically and confirmed onscreening ECHO

15. RHC contraindicated during the study per Investigator

16. Cerebrovascular accident within 3 months (120 days) of start of Screening

17. History of restrictive or constrictive or congestive cardiomyopathy

18. Left ventricular ejection fraction (LVEF) < 50% on historical echocardiogram (ECHO)performed within 6 months prior to start of Screening period (and confirmed duringthe Screening ECHO) or grade 2 or higher diastolic dysfunction

19. Any current symptomatic coronary disease (myocardial infarction, percutaneouscoronary intervention, coronary artery bypass graft surgery, or cardiac anginalchest pain in the past 6 months (180 days) prior to start of Screening)

20. History of acutely decompensated left heart failure or right heart failure within 90days prior to Baseline, as per Investigator assessment

21. Significant (≥ 2+ [or > mild] regurgitation) mitral regurgitation or aorticregurgitation valvular disease, or more than mild mitral stenosis or aortic stenosisvalvular disease as seen on Screening ECHO

22. Started or stopped receiving any general supportive therapy for PH (e.g., oxygen,anticoagulants, digoxin) within 30 days prior to start of Screening

23. Use of supplemental oxygen > 10 liters/minute and SaO2 < 90% while receiving typicaloxygen supplementation

24. Received intravenous (IV) inotropes (e.g., dobutamine, dopamine, norepinephrine,vasopressin) within 30 days prior to start of Screening

25. History of atrial septostomy within 180 days prior to start of Screening

26. History of portal hypertension or chronic liver disease, defined as mild to severehepatic impairment (Child-Pugh Classes A to C)

27. Untreated, severe (defined as apnea hypoxia index of > 30) obstructive sleep apnea

28. Active daily smoker of cannabis or tobacco

29. Current alcohol abuse or current illicit drug use

30. WHO Group 3 due to severe chronic obstructive pulmonary disease (COPD) or chronicpulmonary fibrosis and emphysema (CPFE) or PFT with FVC < 50% or FEV1/FVC < 65% orDLCO < 25% (corrected for Hb g/dl)

31. Presence of lab abnormalities at Screening

32. History of greater than severe renal disease, including any episode of acute renalfailure, with or without a prior history of renal disease in which acute dialysis (e.g., intermittent hemodialysis or continuous veno-venous hemofiltration) wasrequired

33. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 daysprior to Baseline or planned initiation during the study (participants who arestable in the maintenance phase of a program and who will continue for the durationof the study are eligible)

34. Participants who plan to continue, or start during the study, medications which aresensitive cytochrome (CYP) 2D6 substrates with a narrow therapeutic index, such asnortriptyline, venlafaxine, and amitriptyline or CYP1A2 substrates with a narrowtherapeutic index

35. History or presence of impaired cardiac function

36. Participants who plan to donate blood after signing consent for the study and for 28days after their last dose of study drug

Key Inclusion Criteria for Extension Period:

1. Participants must complete the main study period (defined as completion ofassessments through the Week 24 visit)

2. Women of child-bearing potential (WOCBP) must have negative pregnancy test

3. All participants must comply with contraceptive guidance until 28 days after lastdose of study drug for WOCBP and 90 days after the last dose of study drug for males

Key Exclusion Criteria for Extension Period:

1. Participant withdrew from main study period due to an AE related to study drug

2. Female participant who is pregnant, breastfeeding, or intends to conceive during thelong-term extension period

3. Males who do not agree to follow protocol contraception guidelines

4. Any condition that in the opinion of the investigator may pose a risk to theparticipant, interferes with the participant's participation or confoundsassessments of the participant