Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil

One of the greatest impediments to patient treatment satisfaction with current inhaled
treprostinil therapy is inconvenience. Currently, PAH patients using inhaled treprostinil may
require more than 36 breaths per day using a nebulizer requiring daily set up and cleaning.
The use of a discrete, hand-held dry powder inhaler to deliver treprostinil to the lungs
could represent a major improvement in convenience and patient satisfaction, thereby
improving the quality of life for PAH patients. Liquidia is pursuing approval of LIQ861, an
inhalation dry powder formulation of treprostinil that is produced using Liquidia's PRINT®
Technology (Particle Replication in Nonwetting Templates), as an alternative to current
inhaled treprostinil therapy for the treatment of patients with PAH (WHO Group 1).

Inclusion Criteria:

- signed informed consent by patient prior to study enrollment

- 18 years of age or older

- If female of childbearing potential, a negative pregnancy test at the Baseline Visit
and agrees to practice adequate birth control throughout the duration of the study. If
the patient is postmenopausal or has documented surgical sterilization, a pregnancy
test and birth control is not necessary.

- The patient has been diagnosed with PAH belonging to the following subgroups of the
updated Nice Clinical Classification Group 1 (Simonneau, Gatzoulis et al. 2013), which
include:

1. Idiopathic PAH (1.1), or

2. Heritable PAH (1.2), or

3. Drug and toxin induced PAH (1.3), or

4. PAH associated with connective tissue disease (1.4.1), HIV infection (1.4.2), or
congenital heart disease (1.4.4) with simple systemic-to-pulmonary shunt at least
1 year after surgical repair

- The patient has been diagnosed with PAH and is NYHA Functional Class II - IV at
Screening.

1. has documented stable doses of approved inhaled therapy for at least 3 months
prior to screening and is willing and able to transition from their prescribed
dose of inhaled therapy to study drug, or

2. has documented stable doses of no more than two approved oral therapies for at
least 3 months prior to screening and is willing and able to add LIQ861 to their
treatment regimen.

- The patient can complete a baseline six-minute walk distance (6MWD) ≥ 150 m.

- The patient has had evidence of FEV1 ≥ 60% and FEV1/FVC ratio ≥ 60% during the 6-month
period prior to enrollment.

Exclusion Criteria:

- The patient's clinical condition is such that, in the opinion of the Investigator,
they are not expected to remain clinically stable for the duration of the study.

- Patients with PH in the Updated Nice Classification Groups 2-5, or PAH Group 1
subgroups not covered by the inclusion criteria (e.g., associated with portal
hypertension [1.4.3] or with schistosomiasis [1.4.5]).

- The patient is currently taking oral prostacyclin analogues or agonists, including
treprostinil and selexipag.

- The patient has had any PAH medication (except for anticoagulants) discontinued within
14 days of Baseline.

- The patient has had a new type of chronic therapy (including but not limited to
oxygen, a different class of vasodilator, diuretic, digoxin, and digitalis) for
pulmonary hypertension added within 30 days of Baseline.

- The patient has uncontrolled systemic hypertension as evidenced by persistent systolic
blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100
mmHg.

- The patient has a history of hemodynamically significant left-sided heart disease
including, but not limited to: aortic or mitral valve disease, pericardial
constriction, restrictive or congestive cardiomyopathy, or coronary artery disease
(CAD).

- The patient has had an atrial septostomy.

- The patient has any serious or life-threatening disease other than conditions
associated with PAH (e.g. malignancy requiring aggressive chemotherapy, end stage
renal disease, etc.).

- The patient is taking any excluded medications listed in the Investigator's Brochure,
namely inhibitors and inducers of CYP2C8

- The patient has a hypersensitivity or allergy to any of the ingredients of LIQ861 or
other clinically relevant allergies (clinical relevance per Investigator judgment).

- The patient has had a pulmonary infarction (defined as infarction in more than one
lung segment documented by V/Q scan or pulmonary angiography) within two weeks of
Screening.

- The patient has had a stroke or transient ischemic attack (TIA) within six months of
Screening.

- The patient has evidence of an active uncontrolled sepsis or systemic infection during
Screening.

- The patient is pregnant or lactating.

- The patient has any musculoskeletal disease or any other disease that would limit
ambulation.

- The patient has participated in an investigational product or device study within the
30 days prior to Screening.

- The patient has current evidence of drug abuse in the opinion of the Investigator.

- The patient has severe hepatic impairment as evidenced by any history of ascites AND
encephalopathy.

- The patient has severe renal impairment (eGFR < 35).

- The patient is taking inhaled treprostinil doses of greater than 90 μg (more than 15
breaths).

Additional Exclusion Criteria for PK Sub-Study:

- The patient meets any of Primary Exclusion Criteria #1 - 19.

- The patient has moderate or severe renal impairment (eGFR < 60).

- The patient is taking inhaled treprostinil doses of greater than 72 μg (more than 12
breaths).