Overview

This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and potential efficacy of ENV-294 in adults with moderate to severe asthma who are receiving background treatment with inhaled corticosteroids (ICS) and long-acting beta₂-agonists (LABA).

Participants will take oral ENV-294 or placebo once daily for 12 weeks. The study includes a screening period of up to 28 days before randomization to confirm eligibility. Study visits and assessments will be conducted to monitor safety, measure drug levels in the blood, and evaluate effects on asthma control and lung function.

Eligibility

Inclusion Criteria:

• Able to read, understand, and sign an informed consent form before any study procedures.
• Male or female adults aged 18 to 75 years with a physician diagnosis of moderate to severe asthma for at least 12 months.
• Receiving stable treatment with an inhaled corticosteroid (ICS) plus a long-acting beta₂-agonist (LABA) for at least 2 months before screening.
• Pre-bronchodilator FEV₁ between 50% and 80% of predicted normal at screening and baseline.
• Demonstrated bronchodilator reversibility, defined as ≥12% and ≥200 mL improvement in FEV₁ (or ≥20% increase in peak expiratory flow) after short-acting bronchodilator use.
• ACQ-5 score ≥1.25 and ≤3.0 at screening and baseline.
• History of at least one asthma exacerbation in the past 12 months requiring systemic corticosteroids or hospitalization/emergency care.

Exclusion Criteria:

• Had a moderate or severe asthma exacerbation within 4 weeks before screening.
• Have a history of life-threatening asthma, including intubation or respiratory arrest.
• Have any other significant pulmonary disease (e.g., COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, tuberculosis, lung cancer, or eosinophilic syndromes).
• Had bronchial thermoplasty within 2 years before screening.
• Used biologic therapies for asthma (e.g., benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab, or tezepelumab) within 6 months or 5 half-lives prior to baseline.
• Require immunosuppressive medications or frequent systemic corticosteroids (more than 3 courses in the past 6 months).
• Are current smokers or former smokers with \>10 pack-year history or who quit within 6 months before screening.
• Have uncontrolled hypertension (systolic ≥160 mmHg or diastolic \>95 mmHg).
• Have significant hepatic impairment or any other condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.