Allogeneic Human Cells (hMSC)in Patients With Idiopathic Pulmonary Fibrosis Via Intravenous Delivery (AETHER)

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and debilitating lung disease
characterized by interstitial fibrosis with decreasing lung volumes and pulmonary
insufficiency eventually resulting in death. Patients with Idiopathic Pulmonary Fibrosis
(IPF) typically present with complaints of sub acutely progressive dyspnea and non-productive
cough, often accompanied by digital clubbing. Due to the insidious onset of symptoms,
however, most patients are diagnosed at late stages of the disease after significant fibrosis
has occurred. Physical exam is characterized by hypoxemia, "dry" inspiratory crackles on
auscultation, and occasional digital clubbing (6). Pulmonary function tests (PFTs) usually
reveal restrictive lung physiology with progressive decline of forced vital capacity (FVC),
diffusion capacity (DLCO) and six-minute walk distances. Diagnosis is established by the
pathologic finding of usual interstitial pneumonia (with sub epithelial fibroblastic foci) by
open lung biopsy (7), and/or by high resolution CT (HRCT) demonstrating the characteristic
findings of peripheral/basal sub pleural reticulonodular changes with fibrosis, honeycombing,
and traction bronchiectasis (8, 9).

The prognosis for patients with Idiopathic Pulmonary Fibrosis (IPF) is uniformly poor. The
natural history of the disease is characterized by inexorable progressive decline
interspersed with "exacerbations" or periods of accelerated disease which are often fatal
(5). There are no FDA approved treatment options for patients with Idiopathic Pulmonary
Fibrosis (IPF) and thus no standard of care. In cases of patients under the age of 60 with
limited comorbid disease, lung transplant may be offered. Patients with Idiopathic Pulmonary
Fibrosis (IPF) receive empiric treatment, supportive care alone, and more recently, are
offered enrollment in clinical trials.

The pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) is characterized by epithelial cell
injury and activation with interstitial inflammation, fibroblast proliferation with
extracellular matrix collagen deposition, and eventual loss of function. Because mesenchymal
stem cells are known to home to sites of injury, inhibit inflammation, and contribute to
epithelial tissue repair, their use has been suggested as a novel therapy for the treatment
of Idiopathic Pulmonary Fibrosis (IPF).

Inclusion Criteria:

- Provide written informed consent.

- Subjects age equal to or greater than 40 and equal to or less than 90 years at the
time of signing the Informed Consent Form.

- Have a clinical diagnosis of Idiopathic Pulmonary Fibrosis (IPF) prior to screening

- Forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity (DLCO) ≥30%
(corrected for hemoglobin but not alveolar volume).

- RVSP equal to or less than 50 mmHg, as documented by Doppler echo or right heart
catheterization.

- Female subjects must be surgically sterile or post-menopausal (greater than 1 year).

Exclusion Criteria:

- HRCT and/or surgical lung biopsy results inconsistent with the diagnosis of IPF.

- Infiltrative lung disease of any type other than Idiopathic Pulmonary Fibrosis (IPF),
lungs disease related to fibrogenic agents, toxins, drugs or other exposures,
granulomatous lung disease, pulmonary vascular disease, or known connective tissue
disease.

- Inability to perform any of the assessments required for endpoint analysis (report
safety or tolerability concerns, perform pulmonary function tests or high resolution
CT (HRCT), undergo blood draws, read and respond to questionnaires.

- Currently receiving (or received within four weeks of screening) any medication,
treatment, or experimental agents for the treatment of Idiopathic Pulmonary Fibrosis
(IPF), except for patients receiving non drug therapies will include oxygen saturation
therapy (oxygen supplementation) and pulmonary rehabilitation.

- Active listing (or expected future listing) for transplant of any organ.

- Clinically important abnormal screening laboratory values, including but not limited
to: hemoglobin <8 g/dl, white blood cell count <3000/mm3, platelets <80,000/mm3, INR >
1.5, aspartate transaminase, alanine transaminase, or alkaline phosphatase > 3 times
upper limit of normal, total bilirubin > 1.5 mg/dl.

- Serious comorbid illness that, in the opinion of the investigator, may compromise the
safety or compliance of the patient or preclude successful completion of the study.
Including, but not limited to: HIV, advanced liver or renal failure, class III/IV
congestive heart failure, myocardial infarction, unstable angina, or cardiac
revascularization within the last six months, or severe obstructive ventilatory
defect.

- Any other condition that, in the opinion of the investigator, may compromise the
safety or compliance of the patient or preclude successful completion of the study.

- Have known allergies to penicillin or streptomycin.

- Be an organ transplant recipient.

- Have a clinical history of malignancy within 5 years (i.e., patients with prior
malignancy must be disease free for 5 years), except curatively- treated basal cell
carcinoma, squamous cell carcinoma, or cervical carcinoma.

- Have a non-pulmonary condition that limits lifespan to less than 1 year.

- Have a history of drug or alcohol abuse within the past 24 months.

- Be serum positive for Human immunodeficiency virus (HIV), hepatitis BsAg or Viremic
hepatitis C.

- Be currently participating (or participated within the previous 30 days) in an
investigational therapeutic or device trial.

- Be a female who is pregnant, nursing, or of childbearing potential while not
practicing effective contraceptive methods. Female patients must undergo a blood or
urine pregnancy test at screening and within 36 hours prior to injection.

- Female subjects must have a FSH less than 25.8 IU/L

- Subject with hypersensitivity to dimethyl sulfoxide (DMSO)

- Saturated oxygen (SpO2 of less than 93% (room air [sea level] at rest). SpO2 of less
than 88% (room air [>5,000 feet above sea level (1524 meters) at rest).