A Study to Investigate MBS2320 Patients with IPF

Prior treatment

• Use of strong CYP3A4 inhibitors/inducers within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of strong CYP3A4 inhibitors/inducers that are prohibited for concomitant use.
• Use of uridine 5’-diphospho-glucuronosyltransferase (UGT)2B7 inhibitors within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of UGT2B7 inhibitors that are prohibited for concomitant use.
• Systemically administered CA inhibitors within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of CA inhibitors that are prohibited for concomitant use.
• A live virus vaccination within the 90 days prior to the baseline visit (1 year for Bacillus Calmette-Guerin vaccination) or intent to receive a live virus vaccination during the study or within 28 days after study completion
• Participation in another clinical study (including attending follow-up visits) or receipt of any investigational drug within a minimum of 90 days or 5 half-lives of the drug (whichever is longer) prior to the baseline visit.
• Previously received MBS2320.
• Donated blood in the 90 days prior to screening.
• Active infection that is clinically significant in the Investigator’s opinion, or any infection requiring hospitalization or treatment with intravenous antimicrobials ≤60 days of screening, or any infection requiring oral antimicrobial therapy ≤2 weeks of the baseline visit.
• Prior GI surgeries or any GI procedures/conditions that may cause concerns with absorption of the study drug.
• History of major surgery (requiring regional block or general anesthesia) within 3 months prior to screening or planned major surgery during the study.
• A significant history of alcoholism or drug/chemical abuse within 1 year prior to screening, as determined by the investigator.
• Participants with chronic obstructive pulmonary disease (COPD) or asthma that: • require >2 maintenance therapies • have experienced an exacerbation requiring hospitalization or systemic corticosteroids within 12 months prior to screening. Patients with COPD that have had an exacerbation treated with antibiotics are also excluded.
• Is receiving systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks of baseline.
• Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline.

Other illness

• Any current malignancy or a history of malignancy within the previous 5 years prior to screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
• Female participants of childbearing potential who do not agree to use a highly effective method of birth control (i.e., contraceptive measure with a failure rate of <1% per year) in conjunction with male contraception (i.e., a condom with spermicidal foam/gel/film/cream/suppository) from the time of the first dose until 90 days after the final dosing occasion.
• Risk factors for severe COVID-19, which in the opinion of the Investigator would put the participant at risk by participating in the study
• Significant history of drug allergy, including to MBS2320 or excipients, as determined by the Investigator.
• Allergic reaction, anaphylaxis, or other reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis or leukopenia) to sulfonamide drugs.
• History of opportunistic, chronic, or recurrent infections including untreated latent tuberculosis.
• Are uncontrolled in the opinion of the investigator.Positive serology results for hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb), hepatitis C (HCV) antibody with positive confirmatory test for HCV (e.g., polymerase chain reaction [PCR]), or human immunodeficiency virus (HIV) antibody at the screening visit. Note: Participants with a positive HbcAb and a negative HbsAg can be included in this the study if HbsAb is positive (considered immune after a natural infection). Participants with negative confirmatory test for HCV can be included in this clinical study.
• Applicable in France only: a. persons deprived of their liberty by judicial or administrative decision b. persons under psychiatric care without their consent (as per Articles L.3212-1, L.3213-1 and L.1121-8) c. persons admitted to a health or social institution for purposes other than research d. adults subject to a legal protection measure (guardianship, curatorship, etc.) e. persons unable to give their consent f. persons who are not affiliated to a social security scheme or who are beneficiaries of such a scheme.
• Any clinically significant neurological, GI, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, hematological, ophthalmic, or other major disorder which, in the opinion of the Investigator, would put the participant at risk by participating in the study (except for IPF or disorders associated with IPF that, in the Investigator’s opinion, do not constitute a risk when taking the study treatments and would not interfere with the study objectives).

Lab values

• Abnormality in heart rate, blood pressure or 12-lead ECG at screening that in the opinion of the Investigator increases the risk of participating in the study. Specific 12-lead ECG exclusion criteria are participants with QT corrected using Fridericia’s formula (QTcF) of >450 ms (males) or >460 ms (females) and participants with PR interval of >220 ms at screening (1 repeat assessment is allowed).
• Screening laboratory values meeting the following criteria: • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 ×ULN or total bilirubin >1.5 × ULN; • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula ≤60 mL/min/1.73 m²; • Total white blood cell count <3,000/µL; • Absolute neutrophil count <1,500/µL; • Platelet count <100,000/µL; • Absolute lymphocyte count <800/µL; • Hemoglobin <9 gm/dL. • Serum bicarbonate ≤20 mmol/L or ≥29 mmol/L. Note: One repeat assessment of any screening laboratory test is acceptable as long as, in the Investigator’s opinion, this does not constitute a risk when taking the study medication and would not interfere with the study objectives.

Other

• Emphysema ≥50% on hrCT or the extent of emphysema is greater than the extent of fibrosis according to the central reviewer’s assessment from the most recent hrCT or if reported by the local reviewer.
• Has a known post bronchodilator (short acting beta agonist [SABA] – albuterol or salbutamol) increase in FEV1 of >10% and in FVC of >7.5%
• Current use of tobacco products and/or vaping.
• Male participants who have not undergone a vasectomy and do not agree to use appropriate contraception (i.e., a condom with spermicidal foam/gel/film/cream/suppository) with their partners of childbearing potential or partners sterilized by tubal ligation, or who do not agree to use an additional highly effective method of contraception with their partners of childbearing potential.
• Male participants who do not agree to refrain from donating sperm from the time of the first dose until 90 days after the final dosing occasion.
• Participants who are breastfeeding or lactating.
• Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
• Have experienced clinically significant metabolic acidosis in the past.
• Baseline resting oxygen saturation is <89% on room air or supplemental oxygen up to a maximum of 4 L/min.
• Unable to refrain from use of the following: • Short acting bronchodilators (e.g., salbutamol/albuterol, ipratropium) on the day of and within 8 hours of pulmonary function tests (PFTs), DLCO, and 6MWTassessments. • Long-acting bronchodilators with twice daily administration (e.g., salmeterol, formoterol, aclidinium) on the day of and within 12 hours of PFTs, DLCO, and 6MWT assessments. • Ultra-long-acting bronchodilators with once daily administration (e.g., tiotropium, vilanterol) on the day of and within 24 hours of PFTs, DLCO, and 6MWT assessments.

• Participant must be 40 years or older at the time of signing the informed consent.
• Has a life expectancy of at least 12 months (in the opinion of the investigator).
• According to the investigator’s best judgment, can comply with the requirements of the protocol
• Diagnosis of IPF based on: a. ATS/ERS/JRS/ALAT guidelines (Raghu, 2022) as confirmed by the investigator based on chest high-resolution computed tomography (hrCT) scan taken within
• Has an FVC ≥45% of predicted.
• Has a DLCO corrected for hemoglobin ≥25% and ≤80% of predicted.
• Minimum distance on 6MWT of 150 meters.
• Has a FEV1/FVC ratio >0.70.
• If on anti-fibrotics, only the approved treatments of nintedanib or pirfenidone are allowed. Participants must be on a stable dose for at least 8 weeks prior to Visit 1 and during Screening and are predicted to remain stable during the course of the study. A combination of both pirfenidone plus nintedanib is not allowed. Where approved, patients not currently receiving treatment with pirfenidone or nintedanib therapy should have a valid reason: this includes contraindication to therapy (including concerns around DDI), previous treatment discontinued due to lack of response or tolerability, not meeting national or regional eligibility criteria for anti-fibrotic treatment, or patient choice.
• Male and female participants using contraception in line with local regulations regarding the methods of contraception for those participating in clinical studies (Appendix 4).
• Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.