A Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A Inhalation Solution in the Treatment of Bronchiolitis Obliterans Syndrome in Patients Post Double Lung Transplant

Regardless of treatment allocation, all patients will continue to receive their SoC regimen
for maintenance of the lung allograft. Eligible patients for the clinical trial must have a
tacrolimus-based triple-drug therapy in combination with mycophenolate mofetil or its
equivalent and a corticosteroid.

A total of 11 visits will be performed during the clinical trial. After informed consent has
been obtained, a Screening Visit will be carried out in order to check general eligibility
for participation. At the Randomization Visit, inclusion and exclusion criteria will be
re-checked and spirometry performed. During the 48-week treatment period, visits are
scheduled every 4-8 weeks. If a patient has an event that meets one of the criteria for
progression of BOS, he/she will return to the clinic within 2-weeks for an unscheduled visit
to have spirometry and other procedures performed.

Inclusion Criteria:

1. Adult patients of ≥ 18 years.

2. Patients with diagnosis of BOS Grade 0-p with screening FEV1 between 85-81% of
personal best FEV1 value post-transplant plus risk factors as defined below, OR BOS
Grade 1 with screening FEV1 between 80-66% of personal best FEV1 value
post-transplant. Patients with diagnosis of BOS Grade 0-p must have >/=2 of these risk
factors for BOS:

- Primary graft dysfunction (PGD)

- Acute cellular rejection

- Lymphocytic bronchiolitis

- Humoral rejection (e.g. de novo anti-human leukocyte antigen antibodies)

- Gastro-oesophageal reflux and microaspiration

- Infection (Viral, Bacterial, Fungal)

- Persistent neutrophil influx and sequestration (bronchoalveolar lavage
neutrophilia)

- Autoimmunity (collagen V sensitization)

3. Patients with an FEV1/FVC ratio of < 0.8.

4. Patients in whom the diagnosis of BOS has been confirmed by the elimination of other
possible causes of obstructive lung disease.

5. Patients with a diagnosis of BOS 0-p or BOS 1 made at least 1 year after transplant
surgery and within 6 months prior to the Screening Visit.

6. Patients receiving a tacrolimus-based basic immunosuppression regimen in combination
with MMF (or equivalent) and corticosteroids. This basic immunosuppression regimen
must be stable (without changes to doses) for at least 4-weeks prior to Randomization.

7. Patients must consent to retrieve prespecified data from the historic medical record
(e.g., information related to the transplant surgery; spirometry data; medication
use).

8. Patients must be receiving prophylaxis against Cytomegalovirus (CMV) and Pneumocystis
pneumonia.

9. Patients capable of understanding the purposes and risks of the clinical trial, who
have given written informed consent and agree to comply with the clinical trial
requirements/visit schedules, and who are capable of aerosol inhalation.

10. Women of childbearing potential must have a negative serum pregnancy test within 7
days prior to randomization and must agree to use one of the methods of contraception
listed in Appendix II of the protocol for their duration of clinical trial
participation.

11. Patients have no concomitant diagnoses that are considered fatal wtihin one year (12
months).

Exclusion Criteria:

1. Patients with confirmed other causes for loss of lung function, such as infection,
acute rejection, restrictive allograft syndrome (RAS), etc.

2. Patients with Cystic Fibrosis.

3. Patients with donor-specific antibody (DSA) positivity at the Screening Visit.

4. Active bacterial, viral, or fungal infection not successfully resolved at least 4
weeks prior to the Screening Visit.

5. Mechanical ventilation within 12 weeks prior to Randomization.

6. Patient has baseline resting oxygen saturation of < 89% on room air or use of
supplemental oxygen.

7. History or presence of bronchial strictures or airway stents or airways requiring
balloon dilatations to maintain patency.

8. Known hypersensitivity to L-CsA or to cyclosporine A.

9. Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/ dL, or
requiring chronic dialysis.

10. Patients with liver disease and serum bilirubin > 3-fold upper normal value or
transaminases > 2.5 upper normal value.

11. Patients with a history of malignancy, including post-transplant lymphoproliferative
disorder, with the exception of treated, localized basal and squamous cell carcinomas.

12. Pregnant women or women who are unwilling to use appropriate birth control to avoid
pregnancy over the course of the clinical trial.

13. Women who are currently breastfeeding.

14. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to
the Screening Visit. This is defined as any treatment that is implemented under an
Investigational New Drug (IND) or compassionate use.

15. Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS
within 2 months prior to Randomization.

16. Patients who are currently participating in an interventional clinical trial.

17. Psychiatric disorders or altered mental status precluding understanding of the
informed consent process and/or completion of the necessary procedures.

18. Any co-existing medical condition that in the Investigator's judgment will
substantially increase the risk associated with the patient's participation in the
clinical trial.