Treprostinil Therapy For Patients With Interstitial Lung Disease And Severe Pulmonary Arterial Hypertension

Patients with pulmonary hypertension complicating pulmonary fibrosis are at increased risk of
death. There are no therapies proven to be effective in this population, targeting the
pulmonary hypertension. The purpose of this study is to evaluate parenteral treprostinil in
an open-label fashion in patients with pulmonary fibrosis and an advanced PH phenotype.

Inclusion Criteria:

Eligible subjects must have IPF and severe PAH documented on standard of care right-heart
catheterization (RHC) and planned to receive therapy with treprostinil as recommended by
the treating physician.

1. All subjects must have high resolution CT scan (HRCT) diagnostic of IPF (performed as
part of standard of care evaluation) or if available, biopsy proven histological usual
interstitial pneumonia (UIP).

2. Severe pulmonary arterial hypertension defined as a resting mean pulmonary artery
pressure (mPAP) > 35 mm Hg; AND pulmonary vascular resistance (PVR) > 3 woods-units;
AND pulmonary capillary wedge pressure (PCWP) < 18 mm Hg by right-heart
catheterization (RHC) performed as part of standard of care evaluation.

3. All subjects must be planned to receive treprostinil therapy as recommended by their
treating physician.

Exclusion Criteria:

1. Acute or chronic impairment other than dyspnea (e.g. angina pectoris, intermittent
claudication) limiting the ability to perform standard of care six-minute walk tests
(6MWT).

2. Six-minute walk distance (6MWD) < 50 meters at screening or baseline standard of care
evaluations

3. Standard of care pulmonary function test (PFT) showing forced expiratory volume in one
second (FEV1)/ forced vital capacity (FVC) ratio < 0.65

4. Standard of care pulmonary function test (PFT) showing a residual volume >120%
predicted

5. Standard of care high-resolution chest computed tomography (HRCT) showing emphysema
extent > 30%

6. Any investigational therapy as part of a clinical trial for any indication with 30
days before screening

7. Change in dose of treatment for IPF - investigational agent (gamma interferon-1b,
pirfenidone, etanercept, and any other investigational agent intended to treat IPF),
corticosteroids, or cytotoxic agents, within 30 days before screening. That is,
subjects can be on any of these agents provided the dose is stable for at least 30
days prior to enrollment.

8. Current treatment for pulmonary hypertension with other prostaglandins (epoprostenol
or iloprost)

9. Change in dose of treatment for PAH - (bosentan, sitaxsentan, ambrisentan, tadalafil,
sildenafil, vardenafil, calcium channel blockers, nitrates, digitalis), within 30 days
before screening. That is, subjects can be on any of these agents provided the dose is
stable for at least 30 days prior to enrollment

10. Pulmonary rehabilitation initiated within 30 days of baseline.