Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis

Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),
multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy
adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and
will be followed for 7 days post dose.

The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be
randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7
days after receiving the last dose.

Following the conclusion of the respective SAD level dose groups the food effect portion of
the study will be initiated and subjects will be randomized to receive an initial single dose
of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an
overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal
(fed group). After a 10 day washout period, subjects will cross over to the opposite group
and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following
dosing.

Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of
PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive
days.

Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK
of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects
will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo
co-administered with PTI-801+PTI-428 or matching placebos.

Part 1 and Part 2 Inclusion Criteria:

1. Adults aged 18 to 55 years old, inclusive, at the time of informed consent

2. Body mass index ≥18 and <30 kg/m2

3. Subject must be a non-smoker and non-tobacco user for a minimum of 30 days prior to
screening and for the duration of the study.

4. Subject understands the full nature and purpose of the study, including possible risks
and side effects, and is willing and able to comply with all compulsory study
procedures and provides informed consent/permission prior to any study procedures
being performed.

5. Females of childbearing potential and males capable of fathering a child must meet the
contraception requirements

Part 1 & Part 2 Exclusion Criteria:

1. History or current evidence of any clinically significant cardiac, endocrinologic,
hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic,
dermatologic, psychiatric, renal, or other major disease, as determined by the
investigator

2. Prolonged QT interval with Fridericia's correction >450 msec at screening

3. Abnormal liver function as defined by aspartate transaminase (AST), alanine
transaminase (ALT), or bilirubin >1.5× the upper limit of the normal range

4. Abnormal renal function at screening defined as creatinine clearance <90 mL/min using
the Cockroft-Gault equation

5. Clinically significant screening results that would exclude subject from the study
(e.g., medical histories, PE, ECGs, vital signs, and laboratory profiles) as deemed by
the investigator

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

7. History of cancer within the past 5 years (excluding non-melanoma skin cancer)

8. History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

9. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine
cotinine is the detection mechanism for nicotine], opiates, barbiturates,
amphetamines, and benzodiazepines) or positive alcohol test at screening

10. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C virus antibody (HCVAb)

11. Clinically significant infection within 3 months of screening as determined by the
investigator

12. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or
any components thereof

13. Has donated blood within 3 months of screening or plans to donate blood within 3
months of study completion

14. Pregnant or nursing women

15. Any conditions that, in the opinion of the investigator, would make the subject
unsuitable for enrollment or could interfere with the subject's participation in or
completion of the study

16. Use of prohibited medications within 14 days prior to dosing of study drug

Part 3 CF Inclusion Criteria:

1. Confirmed diagnosis of CF with the F508del/F508del genotype

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

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

Part 3 CF Exclusion Criteria:

1. Participation in another clinical trial or treatment with an investigational agent
within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

2. History of cancer within the past 5 years (excluding cervical cancer in situ with
curative therapy for at least one year prior to screening and non-melanoma skin
cancer)

3. History of organ transplantation

4. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically
significant infection or illness (as determined by the investigator) requiring an
increase or addition of medication, such as antibiotics or corticosteroids, within 14
days of Day 1

5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,
azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy
(excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1

6. History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

7. Pregnant or nursing women

8. Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of
study drugs