An Open Label Trial Evaluating the Safety, Tolerability, Efficacy and Pharmacokinetic Profile of Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients

Inclusion Criteria:

1. Provide written informed consent to participate and is willing and able toparticipate in the study and abide by study restrictions in the judgement of theInvestigator.

2. Males or females aged 18 or over at time of screening.

3. Continuous non-smoker who has not used nicotine-containing products (includinge-vaping) for at least 12 weeks prior to the first dosing and throughout the study,based on patient's self-reporting and urine cotinine levels at screening and Day 1.

4. Have undergone bilateral allograft lung transplantation at least six months prior toenrolment and meet all of the following:

5. Receiving oral immediate-release or oral extended-release (not intravenous [IV]or sublingual) tacrolimus immunosuppression at a stable dose for 3 weeks priorto first dosing according to institutional standards as part of animmunosuppressive regimen along with mycophenolate mofetil or azathioprine andcorticosteroids

6. Demonstrating elevated markers of renal dysfunction: blood serum creatinine > 124 μmol/L (0.14 mg/dL) or estimated glomerular filtration rate (eGFR) < 45

7. Stable to enable routine post-treatment bronchoscopy with BAL and EBB. Biopsyis not required in patients with significant increased risk of bleeding afterSponsor Medical Monitor approval.

8. Screening FEV1 and forced vital capacity (FVC) values ≥ 40% predicted (toassure viable graft)

9. Females (women) of child-bearing potential (WOCBP) are defined as those who haveexperienced menarche and who have not undergone surgical sterilization (hysterectomyor bilateral oophorectomy) and who are not post-menopausal. WOCBP must have anegative serum pregnancy test at Screening and a negative urine pregnancy test atDay 1 and must agree to practice contraception as defined below if sexually activewith males. In addition, no WOCBP may be planning a pregnancy during the studyperiod.

10. Female subjects who are WOCBP must agree to use highly effective contraceptivemethods or abstinence for the duration of time on the study and continue to useacceptable contraceptive methods for 3 months after administration of the lastdose of study treatment. Highly effective contraception is defined as use ofthe 2-barrier method (e.g., female diaphragm and male condom), 1 barrier methodwith spermicide, intrauterine device, or hormonal contraceptives (e.g., implantor oral). If the subject is using a hormonal form of contraception, use musthave been stable for at least 4 weeks prior to screening.

11. Abstinence will be acceptable only if it is in line with the preferred andusual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation)and withdrawal are not acceptable methods of contraception.

12. Post-menopausal females are eligible if they meet the definition of menopause (at least 12 months of amenorrhea in the absence of other biological causes)and for females < 55 years of age, must also have a documented serum folliclestimulating hormone (FSH) level of > 40mIU/mL at Screening.

13. Male subjects with female partners of childbearing potential must be congenitallysterile or surgically sterile (vasectomy with confirmation of aspermia) or agree touse 2 effective methods of contraception including 1 barrier method (e.g., condomwith spermicide and contraception by female partner) for the duration of time on thestudy and for 3 months after administration of the last dose of study treatment. Useof a condom is required by men during intercourse with a male or female partner toprevent potential delivery of the drug via seminal fluid during the study until theend of treatment visit.

14. If male, must agree not to donate sperm from the first dosing until 90 days afterthe last dosing.

15. Able to successfully perform spirometry, use the inhalation device, and comply withstudy restrictions and visit schedule.

Exclusion Criteria:

1. Active antibody-mediated rejection (AMR) or any other evidence of acute rejection

2. Active bacterial, viral or fungal infection not successfully resolved at least 4weeks prior to study entry.

3. Presence of uncontrolled gastro-esophageal reflux disease (GERD)

4. History or presence of hypersensitivity or idiosyncratic reaction to tacrolimus orany calcineurin inhibitor.

5. Received a treatment with other investigational drug within 5 times the eliminationhalf-life, if known (e.g., a marketed product) or within 30 days (if the eliminationhalf-life is unknown), whichever is longer, prior to Study Day 1 dosing.

6. Positive for hepatitis B surface antigen (HBsAg) PCR, hepatitis C PCR, and humanimmunodeficiency virus (HIV) I and II antibodies, tuberculosis (TB), or COVID-19 atScreening.

7. Patients who have taken any of the following prohibited medications within 30 daysof the first dose or who are expected to require these medications during the study:

8. Cyclosporin

9. Any form of sirolimus or everolimus

10. Allergy or sensitivity to lactose or milk products.

11. Clinically significant hepatic impairment defined as 5 times the upper limit ofnormal (ULN) for ALT and AST.

12. Patients receiving haemodialysis or peritoneal dialysis

13. Active post-transplant lymphoproliferative disorder (PTLD) related to Epstein-BarrVirus (EBV) infection.

14. Subjects with significant electrocardiogram (ECG) abnormalities at screening,including a QT interval corrected by the Fridericia correction formula that is ≥ 440msec in men and ≥ 460 msec in women.

15. Demonstrates an inability to operate the inhalation device after training.