Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults

An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the
safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF.
All patients will remain on their CF standard-of-care treatments over the trial duration.

The goal for the treatment with LAU-7b in CF is to preserve lung function by reducing the
persistent inflammation in the lung and to improve its capacity to defend against resistant
bacteria such as Pseudomonas aeruginosa.

The treatment regimen will consist of 6 consecutive "dosing cycles" of 21 days each, spaced
by study drug-free periods of 7 days. A total of 136 eligible adult patients with CF will be
randomized to receive 300 mg LAU-7b or placebo in a 1:1 ratio. The participation in the study
will last about 7 months.

Inclusion Criteria:

- Screening FEV1 between 40% and 100% predicted value for age, gender and height, in
patients capable of properly performing the test;

- History of pulmonary exacerbation, defined as at least one (1) pulmonary exacerbation
in the year prior to Screening which resulted in documented intravenous antibiotics;

- Patients are eligible independently of their history of pulmonary Pseudomonas
aeruginosa (PsA) infection and their PsA status at screening;

- If taking Kalydeco® (ivacaftor), Orkambi® (ivacaftor/lumacaftor) or Symdeko®
(ivacaftor/tezacaftor), patients must be taking it for a minimum of 3 months prior to
screening, and deemed to tolerate it;

- No change in CF and allowed systemic chronic therapy for a minimum of 1 month prior to
screening;

- Female patients of child bearing potential should be on highly effective contraceptive
methods during the study;

- Male patients with spouse or partner of child bearing potential, or pregnant, are
eligible if they use an appropriate method of contraception.

Exclusion Criteria:

- Pregnancy: due to the potential teratogenic effects of retinoids, pregnant women are
NOT eligible;

- Breast milk feeding by study patient is NOT allowed;

- Clinically abnormal renal function: serum creatinine > 132 μM (1.5 mg/dL);

- Clinically abnormal liver function: Total bilirubin >1.5 x ULN (in the absence of
demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate
aminotransferase (AST) > 2.5 x ULN;

- Patients with plasma retinol levels below 0.7 µM;

- Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal,
ophthalmological condition;

- Presence of serious dermatological conditions at entry, including inflammatory or
xerotic skin pathologies such as psoriasis or ichthyosis;

- Intake of chronic systemic steroids in the month prior to screening and during the
study;

- History of acute infections (viral/bacterial/fungal) within 1 month prior to
screening, whether or not treated and resolved;

- Presence of infection with Burkholderia cepacia (including all species within the
Burkholderia cepacia complex group, and Burkholderia gladioli) in the 12 months prior
to screening;

- Patients with a confirmed diagnosis (as per the Cystic Fibrosis Foundation diagnostic
criteria) of Allergic BronchoPulmonary Aspergillosis (ABPA) and actively being treated
with corticosteroids and/or anti fungal agents.