Study of ENV-294 in Adults With Moderate-to-Severe Atopic Dermatitis

Incidence and Severity of Adverse Events

1\. Number and seriousness of adverse events (AEs), serious adverse events (SAEs), and adverse events leading to discontinuation of study drug.

Time frame: Baseline to Week 12 (Day 85)

To evaluate how well ENV-294 works in participants with atopic dermatitis during 12 weeks of treatment.

1\. Percentage of participants with at least 75% reduction from Baseline in Eczema Area and Severity Index (EASI) score at Week 12.

Time frame: Baseline to Week 12 (Day 85)

To evaluate pharmacokinetics (PK) using limited blood samples during the 12-week treatment period.

Observed concentration values of ENV-294 at the times blood samples are collected during the 12-week treatment period.

Time frame: Baseline through Week 12 (Day 85)

Observed values, change from baseline, and percent change from baseline in heart rate (beats per minute) as a measure of safety and tolerability of ENV-294.

Heart rate measured from 12-lead ECG recordings in beats per minute to assess cardiac safety and tolerability.

Time frame: Baseline through treatment and the end of study at approximately week 16.

Observed value, change from baseline, and percent change from baseline in systolic blood pressure (mmHg) as a measure of safety and tolerability.

Systolic blood pressure measured in millimeters of mercury (mmHg) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294..

Time frame: Baseline through the end of the treatment period and the end of the study at approximately week16.

To assess the efficacy of ENV-294 in participants with AD over a 12- Week treatment period

Proportion of participants who achieve a ≥2-point reduction from Baseline in Validated Global Investigator Assessment (vIGA) score and a score of 0 or 1 at Week 12

Time frame: Baseline through Week 12

To evaluate how well ENV-294 works in participants with atopic dermatitis during 12 weeks of treatment.

Change and percent change in Patient Oriented Eczema Measure (POEM) at Week 12

Time frame: Baseline through Week 12

To evaluate how well ENV-294 works in participants with atopic dermatitis during 12 weeks of treatment.

Peak Pruritus Numerical Rating Scale (PP-NRS) response status defined as achieving weekly mean decreases of ≥4 points

Time frame: Baseline through Week 12

Observed value, change from baseline, and percent change from baseline in diastolic blood pressure (mmHg) as a measure of safety and tolerability.

Diastolic blood pressure measured in millimeters of mercury (mmHg) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294

Time frame: Baseline through the end of the treatment period at approximately week 16.

Observed value, change from baseline, and percent change from baseline in heart rate (beats per minute) as a measure of safety and tolerability.

Heart rate measured in beats per minute (bpm) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.

Time frame: Baseline throug the treatment period and the end of study at approximately week 16.

Observed value, change from baseline, and percent change from baseline in respiratory rate (breaths per minute) as a measure of safety and tolerability.

Respiratory rate measured in breaths per minute using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.

Time frame: Baseline through the treatment priod and the end of the study at approximately week 16

Observed values, change from baseline, and percent change from baseline in RR interval (milliseconds) as a measure of safety and tolerability of ENV-294.

RR interval measured from 12-lead ECGs in milliseconds (ms) to assess cardiac safety and tolerability.

Time frame: Baseline through treatment and end of study (approximately Week 16).

Observed values, change from baseline, and percent change from baseline in PR interval (milliseconds) as a measure of safety and tolerability of ENV-294.

PR interval measured in milliseconds (ms) using standard 12-lead ECGs to assess safety and tolerability.

Time frame: Baseline through treatment and end of study (approximately Week 16).

Observed values, change from baseline, and percent change from baseline in QRS duration (milliseconds) as a measure of safety and tolerability of ENV-294.

QRS duration measured in milliseconds (ms) using standard 12-lead ECGs to assess cardiac conduction and safety.

Time frame: Baseline through treatment and end of study (approximately Week 16).

Observed values, change from baseline, and percent change from baseline in QT interval (milliseconds) as a measure of safety and tolerability of ENV-294.

QT interval measured in milliseconds (ms) using standard 12-lead ECGs to assess cardiac repolarization safety.

Time frame: Baseline through treatment and end of study (approximately Week 16).

Observed values, change from baseline, and percent change from baseline in QTc Bazett (milliseconds) as a measure of safety and tolerability of ENV-294.

QTc Bazett (QT corrected for heart rate using Bazett's formula) measured in milliseconds (ms) to evaluate cardiac safety.

Time frame: Baseline through treatment and end of study (approximately Week 16).

Observed values, change from baseline, and percent change from baseline in QTc Fridericia (milliseconds) as a measure of safety and tolerability of ENV-294.

QTc Fridericia (QT corrected for heart rate using Fridericia's formula) measured in milliseconds (ms) to evaluate cardiac safety.

Time frame: Baseline through treatment and end of study (approximately Week 16).