Study Assessing PTI-428 Safety, Tolerability, and Pharmacokinetics in Subjects With Cystic Fibrosis

PART A The SAD treatment group is comprised of 3 cohorts where subjects will be randomized to
either PTI-428 or placebo. Following the conclusion of at least 3 SAD treatment groups, a set
of adult subjects diagnosed with CF will participate in an assigned MAD treatment group. The
MAD treatment group is comprised of 3 cohorts. MAD Cohort 1 will enroll adult subjects with
CF currently on stable ORKAMBI® background therapy for a minimum of 3 months at the time of
randomization. MAD Cohorts 2 and 3 will enroll adult subjects with CF who are not currently
on any background therapies. Subjects in all MAD cohorts will be randomized to either PTI-428
or placebo. Each dose will be administered once daily (QD) for a total of 7 Days.

PART B Following the conclusion of MAD Cohort 1, a set of adult subjects diagnosed with CF
currently on stable ORKAMBI® background therapy for a minimum of 3 months will participate in
Part B. The Part B Phase II treatment group is comprised of 2 cohorts where subjects will be
randomized to either PTI-428 or placebo. Each dose will be administered QD for a total of 28
days.

PART C Following the conclusion of Part B Phase II, a set of adult subjects diagnosed with CF
will participate in Part C. The Part C Phase II treatment group is comprised of 3 cohorts.
Part C Cohort 1 will enroll adult subjects with CF who are eligible to take, but not
currently taking, ORKAMBI® in accordance with the approved label. Part C Cohort 2 will enroll
adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3
months at the time of randomization. Part C Cohort 3 will enroll adult subjects with CF who
are not currently on any background therapies and are pancreatic sufficient. Each PTI-428 or
placebo dose will be administered QD for a total of 28 days.

Inclusion Criteria:

- Confirmed diagnosis of CF.

- Forced expiratory volume in 1 second (FEV1) 40-90% predicted.

- Non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for
the duration of the study.

Exclusion Criteria:

- Participation in another clinical trial or treatment with an investigational agent
within 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.

- History of cancer within the past five years (excluding cervical CIS with curative
therapy for at least one year prior to screening and non-melanoma skin cancer).

- History of organ transplantation.

- Any sinopulmonary infection or CF exacerbation requiring a change or addition of
medication (including antibiotics) within 1 month of Study Day 1 or any other
clinically significant infection as determined by the investigator within 1 month of
Day 1.

- History of alcohol or drug abuse or dependence within 12 months of screening as
determined by the Investigator.

- Male and female of child-bearing potential, unless they are using highly effective
methods of contraception during participation in the clinical study and for 4 weeks
after termination from study.

- Pregnant or nursing women.