Multiple Ascending Dose Study of TRN-157 in Stable Mild and Moderate Asthmatics

Inclusion Criteria:

Patients who meet the following criteria will be considered eligible to participate in the
study:

- The patient is ≥ 18 and < 70 years of age, and gives informed consent

- Clinical diagnosis of mild to moderate asthma of at least 6 months duration and age
of onset < 50 years

- Presently using ICS at moderate doses (equivalent to 200-800 µg of budesonide or
88-500 µg of fluticasone daily)

- ≥ 12% and ≥ 200 mL improvement in FEV1 to 4 puffs albuterol by metered-dose inhaler
(MDI) at screening visit

- Patient is willing to use acceptable form of birth control during trial and for one
month thereafter

- Ability to measure morning (AM) peak expiratory flow (PEF) on schedule using
electronic peak flow meter (EPFM) and to complete the study diary correctly at least
70% of the time during the run-in period

- After 7 day withdrawal from LABA therapy and overnight withdrawal from SABA therapy
(except rescue medication), patient has between 55% - 80% of predicted FEV1 at CV2

Exclusion Criteria:

A patient meeting any of the following criteria is not eligible for enrollment in the
study:

- A clinical diagnosis of chronic obstructive pulmonary disease (COPD), chronic
bronchitis, bronchiectasis, or other significant pulmonary disease other than asthma

- History of upper or lower respiratory infection within 4 weeks of screening

- History of asthma exacerbation requiring oral or systemic corticosteroids or hospital
admission within 6 months of screening

- History of myocardial infarction, or cardiac conduction abnormalities, including but
not limited to atrial fibrillation, and paroxysmal atrial tachycardia

- Hospitalization due to cardiac failure within the last 6 months

- History of narrow angle glaucoma or obstructive uropathy

- Current smokers or vapers, or former smokers with > 10 pack-year (self-reported)
history of smoking

- Patients who presently use the following medications will not be eligible for
participation:

- Long-acting muscarinic receptor antagonist (LAMA)

- LABA (but may be withdrawn and converted to SABA x 7 days prior to entry)

- Leukotriene pathway blockers

- Anti-IgE antibody (Xolair) within last 6 months prior to CV1

- Phosphodiesterase 4 (PDE4) inhibitors (e.g., Roflumilast)

- Cromolyn

- Methylxanthines (e.g., aminophylline and theophylline)

- 5-Lipoxygenase inhibitor (e.g., Zileuton)

- Allergies to LAMA therapies

- History of life-threatening asthma exacerbation requiring ICU admission, mechanical
ventilation, or tracheostomy