Study to Evaluate Safety and Efficacy of Mirivadelgat in PH-ILD (Windward)

1. A clinical diagnosis of PH-ILD.
2. Participant voluntarily gives informed consent.
3. Male or female participants aged between 18 and 85 years at the time of signing informed consent.

4. Participants must agree to practice protocol-defined birth control during the study period, unless they meet criteria for not being of childbearing potential.

   • Male participants with female partners of childbearing potential must practice protocol- defined birth control for the duration of treatment and at least 96 hours after discontinuing the IP.
   • Female participants of childbearing of potential (including those \<1-year post-menopausal) must practice protocol-defined birth control during the conduct of the study and for 30 days after the last dose of IP (males only during exposure to IP).

   • Female participants not of childbearing potential (as defined below) are eligible for enrolment without contraception requirements:

     1. Post-menopausal women (at least 12 months with no menses without an alternative medical cause); in women \<45 years of age, a high follicle-stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy; OR
     2. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
     3. Have a congenital or acquired condition that prevents childbearing.
5. The participant has a confirmed diagnosis of any form of interstitial lung disease based on high-resolution computed tomography (HRCT) of the chest within 180 days prior to screening or at screening or a historical surgical biopsy (or other appropriate tissue sampling (e.g., cryobiopsy). The participant can have other findings (e.g., emphysema) if this is not the predominant feature on the scan.

6. Participants have undergone RHC during the screening period with the following documented parameters:

   • Pulmonary vascular resistance (PVR) ≥4 Wood units and
   • Pulmonary capillary wedge pressure (PCWP) of ≤12 mmHg [if PVR ≥4 Wood units to \<6.25 Wood units] or PCWP ≤15 mmHg [if PVR ≥6.25 Wood units] Note: If a reliable PCWP cannot be obtained, left ventricular end-diastolic pressure (LVEDP), measured via left heart catheterization (LHC), will be acceptable, with the same numerical thresholds as the PCWP criterion: LVEDP of ≤12 mmHg [if PVR ≥4 to \<6.25 Wood units], or LVEDP ≤15 mmHg
   • A mean pulmonary arterial pressure (PAP) of >20 mmHg.
7. Participants must have a 6-minute walk distance ≥100 meters and ≤500 meters at the Screening Visit (Visit 1).
8. Participants agree to a repeat RHC, Chest CT, and MRI prior to study completion.
9. Participants on chronic treatment for underlying lung disease (i.e., nintedanib or pirfenidone or immunosuppressive agents etc.) must be on a stable/optimized dose for ≥30 days prior to screening and have been receiving treatment for ≥90 days.
10. Participants on supportive medications (e.g., inhalers for asthma) must be on stable doses for ≥30 days prior to screening.
11. In the Investigator's opinion, the participant must be able to consent for themselves and communicate with local staff using interpreters if necessary. Participants must agree to attend all study visits and be contactable through a cellular device or landline.
12. Participants must have clinical laboratory values within normal ranges or \<1.5 times the upper limit of normal (ULN) as specified by the testing laboratory.

13. Participants must meet the following requirements for the pulmonary function test (PFT) at screening:

    • Forced vital capacity (FVC) \<90% of predicted
    • Diffusion capacity of carbon monoxide (DLCO) \<70% of predicted, or \<70% of predicted corrected for hemoglobin (Hb), if correction is required. (Correction applies if Hb value is ≥25% and ≤90% of normal.) Note: DLCO must be determined locally at screening, using American Thoracic Society (ATS) standards. Hemoglobin correction should reference ATS normal values: Men = 14.6 g/dL, Women = 13.4 g/dL.
14. Negative serology test for hepatitis B surface antigen and hepatitis C antibody at Screening Visit.

Exclusion criteria:

Medical Conditions

1. Participant has another concomitant diagnosis of pulmonary hypertension not otherwise considered to be PH-ILD. This would include and is not limited to the concomitant presence of thromboembolic disease, untreated/inadequately treated obstructive sleep apnea, human immunodeficiency virus (HIV), methamphetamine or anorexigenic drug use, and other conditions of the WHO Group 1, 2, 4, and 5 classifications.

2. Participant has evidence of clinically significant left-sided heart disease within 6 months of screening as defined by:

   • Left ventricular ejection fraction \<40% as assessed by echocardiography.
   • More than mild left-sided valvulopathy (e.g., worse than mild mitral stenosis or regurgitation and worse than mild aortic stenosis or regurgitation).
   • LVEDP or PCWP >15 mmHg (or >12 mmHg if PVR ≥4 to 6.25 Wood units).

3. Participants must NOT have 3 or more of the following left ventricular disease/dysfunction risk factors at screening:

   • Body mass index (BMI) ≥30 kg/m2.
   • Uncontrolled diabetes, as evidenced by HbA1C >9.5%, or urine glycosuria >1.0 g/dl, or presence of diabetic ketoacidosis.

   • History of significant coronary disease within 6 months of screening as demonstrated by any of the following:

     1. History of myocardial infarction or acute coronary syndrome (unstable angina), or
     2. Percutaneous coronary intervention or percutaneous transluminal angioplasty, or previous coronary artery bypass graft, or
     3. Evidence of coronary artery disease (>50% stenosis in at least one major coronary artery) or abnormal nuclear stress test.
4. The participant is receiving ≥10 L/min of oxygen supplementation by any mode of delivery at rest.
5. The participant has received any PH-approved therapy, including soluble guanylate cyclase inhibitors, endothelin receptor antagonists, or parenteral or oral prostacyclin therapy (excluding vasoreactivity testing) within 60 days of randomization or 5 half-lives. Use of phosphodiesterase type 5 inhibitors and inhaled prostacyclin (e.g., inhaled treprostinil) on stable doses for ≥30 days prior to screening will be allowed irrespective of local approval (as per ESC/ERS 2022).
6. Use of any inhibitors and inducers of cytochrome P450 3A4 (CYP3A4) (e.g., boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, telithromycin, troleandomycin, voriconazole, clarithromycin, idelalisib, nefazodone, nelfinavir, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort). For a comprehensive list, please refer to the FDA's Examples of Drugs that Interact with CYP Enzymes and Transporter Systems (FDA 2025).
7. Recent exacerbation of underlying lung disease or active pulmonary/upper respiratory tract infection within 4 weeks of randomization.
8. Any current active malignancy (this does not include localized cancers such as basal or squamous cell carcinoma of the skin). Any history of malignancy that is likely to result in mortality or require significant medical or surgical intervention within the following year.
9. Chronic kidney disease Stage IV or greater (i.e., eGFR ˂30 mL/min/1.73m2) or evidence of acute kidney injury.
10. The participant has a history of congenital heart disease, irrespective of any prior treatment or surgical intervention
11. Use of tobacco, e-cigarette, nicotine, or marijuana products or a significant history of drug or alcohol abuse within 6 months of screening.
12. Acute pulmonary embolism within 90 days of screening.
13. Participation in pulmonary rehabilitation within 90 days of screening. However, participants who were on stable pulmonary rehabilitation for more than 90 days before screening may be considered for the study, provided they meet all other inclusion criteria.
14. Prior or concurrent use of any investigational drug/device/therapy or participation in any investigational study with therapeutic intent within 30 days or 5 half-lives, whichever is longer, before the first dose of the IP.
15. BMI ≥40 kg/m2.
16. Uncontrolled hypertension as evidenced by systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg during the screening period. Participants who fail screening due to high blood pressure can be re-screened once after their antihypertensive medications have been adjusted and their doses have been stable for at least 4 weeks.
17. Concomitant disease that confers a life expectancy of \<6 months at screening.
18. The Investigator judges that the participant will be unable to fully participate in the study and complete it for any reason, including inability to comply with the study procedures and treatment of addiction or any other relevant medical or psychiatric conditions.
19. High likelihood of lung transplantation (in the opinion of the Investigator) within 4 months after randomization.
20. History of liver dysfunction, including participants with moderate (Child-Pugh B) or severe (Child-Pugh C) impairment or disordered coagulation.
21. Female participants who are pregnant or breastfeeding.
22. Worse than mild untreated sleep apnea (5-14.9 events/hour). Treated sleep apnea is permitted.

23. Participants with a prior diagnosis of connective tissue diseases, e.g., systemic sclerosis (scleroderma), systemic lupus erythematosus, Sjogren's disease, polymyositis/dermatomyositis/antisynthetase syndrome, or rheumatoid arthritis.

    Other Exclusions

24. History of allergic or anaphylactic reaction to mirivadelgat or to any component of the excipient.

25. Previous exposure to mirivadelgat.

    Diagnostic Assessments

26. The following laboratory parameters are excluded:

    • Hemoglobin \<10 g/dL (100 g/L).
    • White blood cells (WBC) \<3000/µL (\<3000/mm3).
    • Platelet count \<70,000/µL (70,000/mm3).
    • Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 or evidence of acute kidney injury.