Biomarker Modulation and the Inhibition of NKT1 Cells by Oral GRI-0621 in Patients With IPF

Inclusion Criteria:

1. Male or female subjects 40 through 85 years of age, inclusive.

2. Confirmed diagnosis of IPF with clinical features consistent with the currentclinical practice guidelines for IPF.

3. FVC > 50% predicted value within 4 weeks of Screening.

4. FEV1/FVC ratio > 0.65 within 4 weeks of Screening.

5. Diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOc) > 30%predicted value within 4 weeks of Screening.

6. Life expectancy of at least 12 months.

7. Willing and able to follow the study required visits and assessments. For Sub-Studysubjects, willing and able to undergo BAL procedures at Screening and at Week 12.

8. Willing and able to provide written informed consent prior to study-relatedprocedures.

Exclusion Criteria:

1. Initiation of any approved or investigational IPF therapy or oral corticosteroids (> 10 mg/day) within 4 weeks of Screening. Subjects already on approved IPF therapiesmust remain on their current medication from Screening until the last study visit.

2. High resolution computerized tomography (HRCT) pattern showing emphysema more thanthe extent of fibrosis of the lung area within 12 months of Screening.

3. Acute exacerbation of IPF within 6 months of Screening (Collard et al., 2016).

4. Requiring supplemental O2 > 4 liters/min to maintain peripheral arterial O2saturation (SpO2) > 88% at rest. O2 saturation at screening or baseline that is < 88% at rest.

5. Any condition with unacceptable risk for bronchoscopy (for Sub-Study subjects only).

6. Current or recent history of clinically significant medical condition, laboratoryabnormality, or illness that could place the subject at risk or compromise thequality of the study data as determined by the Investigator.

7. Significant coronary artery disease (i.e., myocardial infarction within 6 months orunstable angina within 1 month of Screening).

8. An upper or lower respiratory tract infection, presence of or suspected emphysema,within 4 weeks of Screening.

9. Eye exam indicating night blindness within 6 months of Screening, or at Screening.

10. Bone Mineral Density t-score of -4.0 (severe osteoporosis) within 6 months ofScreening, or at Screening.

11. Screening QT of >450 for men and >470 for women.

12. History of renal impairment as deemed clinically relevant by the investigator OReGFR <60ml/min/1.73m2 within 60 days of Screening and a Screening eGFR of <60ml/min/1.73m2.

13. History of hepatic impairment as deemed clinically relevant by the investigator ORALT or AST >2 x ULN OR moderate and severe hepatic impairment as defined using theChild-Pugh scoring system (i.e., Child-Pugh B and C).

14. A history of hypertriglyceridemia (documented TG of >2.0mmol/L at Screening); ahistory of pancreatitis from any cause; uncontrolled dyslipidemia with LDL-c >4.9mmol/L and an HDL-c <1.3 mmol/L for women and <1.0 for men, despite optimizedtreatment.

15. Use of moderate or strong inhibitors of CYP2C8 (e.g. gemfibrazol, trimethoprim,clopidogrel) or inducers of CYP2C8 (e.g. rifampin) from 7 days or 5 half-lives,whichever is longer, before the first administration of GRI-0621 until cessation ofGRI-0621 administration.

16. Subjects who report any active suicidal ideation (SI) or behavior (SB) (i.e.Columbia Suicide Severity Rating Scale (C-SSRS) scores 4 or greater for SI and anypositive scores for SB) during Screening or any past history thereof.

17. Current smoker (i.e., use of tobacco products within the last 3 months) ofScreening.

18. Current or recent history of drug or alcohol abuse within 12 months of Screening.

19. Participation in any other investigational drug study within 4 weeks of Screening orwithin 5 times the elimination half-life of an investigational drug.

20. Females who are pregnant or breastfeeding, or if of child-bearing potentialunwilling to practice two highly effective forms of contraception for at least 1month prior to initiation of the study drug, during the study, and for 1 month afterdiscontinuing the study drug (e.g., abstinence, intrauterine device or system,combination of barrier and spermicide, hormonal contraceptive, surgicalsterilization, or male partner sterilization).

21. Males, if sexually active, unwilling to practice two highly effective forms ofcontraception during the study (e.g., condom, or surgical sterilization).

22. History of hypersensitivity or intolerance to oral tazarotene.