Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)

This is a randomized, placebo-controlled, double-blind phase 2 trial evaluating approximately
76 subjects with symptomatic AERD on the safety and efficacy of 8 weeks of oral ifetroban
treatment. Eligible AERD subjects will be randomized to receive 8 weeks of either oral
ifetroban daily or matching placebo followed by a 2-week post-treatment period.

Inclusion Criteria:

1. History of physician-diagnosed asthma

2. History of nasal polyposis

3. History of at least two reactions to oral aspirin or other nonselective cyclooxygenase
inhibitor with features of lower airway involvement (cough, chest tightness, wheezing,
dyspnea), or one reaction that was life-threatening and required hospitalization, or a
diagnosis of AERD by a physician-conducted challenge to aspirin in the last five years
before starting treatment.

4. Stable asthma (post-bronchodilator FEV1 of ≥ 60%, no glucocorticoid burst for at least
two weeks prior to starting treatment, no hospitalizations or emergency room visits
for asthma at least three months prior to starting treatment and not on a dose >1000
µg fluticasone or equivalent daily).

5. ≥ 18 years of age

6. Exhibit symptomatic AERD within three weeks of starting treatment by demonstrating a
score of at least 20 on the Sino-nasal Outcome Test (SNOT) - 22.

Exclusion Criteria:

1. Current smoking, defined as daily tobacco smoking in the last six months and at least
one instance of tobacco smoking in the last three months.

2. Current pregnancy or breastfeeding

3. Use of oral or systemic steroids (e.g. prednisone or equivalent) > 20 mg daily in the
last four weeks before starting treatment.

4. Daily use of long-acting antihistamines in the last two weeks before starting
treatment.

5. Less than 12 months of allergy shots (maintenance dose of allergy shots are allowed if
treatment duration exceeds 12 months). Less than 1 month of 5-lipoxygenase inhibitors
(e.g. zileuton) and/or leukotriene receptor antagonists (e.g. montelukast).

6. Any use of nonsteroidal anti-inflammatory drugs (NSAIDs) or any drug that inhibits the
cyclooxygenase enzyme in the last two weeks before starting treatment.

7. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs in the
last two weeks before starting treatment.

8. Any immunosuppressive treatment including but not limited to methotrexate,
cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine,
hydroxychloroquine, azathioprine, and cyclophosphamide in the last two weeks before
starting treatment (maintenance dose of allergy shots are allowed if treatment
duration exceeds 12 months). Biologics/immunotherapies such as Xolair or Nucala are
permitted if duration exceeds three months.

9. Endoscopic sinus surgery / polypectomy within the past three months

10. Previously treated in a clinical trial with ifetroban within the past three months.

11. Previously treated with other investigational drugs within eight weeks or five
half-lives, whichever is longer, before screening

12. Conditions/concomitant disease which make them unevaluable for the efficacy endpoints