Long-term Safety and Efficacy Evaluation of APG777 in Patients with Moderate-to-Severe Atopic Dermatitis: An Extension Study

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of APG777 in patients with moderate-to-severe **Atopic Dermatitis** (AD). This is clinically relevant as it aims to ensure that the treatment is safe for extended use, which is crucial for chronic conditions like AD that require long-term management.

Secondary objectives include:

• Evaluating the long-term efficacy of APG777 in patients with moderate-to-severe AD during the Extended Treatment Period.
• Assessing the long-term effect of APG777 on the maintenance of response in the Extended Treatment Period.
• Evaluating the long-term safety and tolerability of APG777 on other safety measures in patients with moderate-to-severe AD.
• Characterizing the long-term pharmacokinetics (PK) of APG777 in patients with moderate-to-severe AD.

The clinical trial involves a total of **271 participants** diagnosed with **Atopic Dermatitis**. The study population includes both male and female subjects, with an age range encompassing children and adults. Participants were selected based on their completion of the Treatment Period in a prior APG777 study and their compliance with the study protocol, as assessed by the Investigator. Additionally, participants are required to continue using the same non-prescription non-medicated emollient or moisturizer from the last day of the Parent Study throughout the long-term extension (LTE) study. The trial does not include a vulnerable population. The primary objective is to evaluate the long-term safety and tolerability of APG777 in patients with moderate-to-severe Atopic Dermatitis.

The clinical trial is designed to evaluate the long-term safety and tolerability of **APG777** in patients with moderate-to-severe **atopic dermatitis**. This study is a Phase 4, randomized, double-blind, controlled trial. Participants who have completed the treatment period in a prior APG777 study and were compliant with the study protocol are eligible for inclusion. The trial is expected to last until December 2029, with recruitment starting in October 2025. The primary endpoint is the number of participants with treatment-emergent adverse events over a period of up to three years. Secondary endpoints include various efficacy measures such as the percentage of participants achieving specific improvements in the Eczema Area and Severity Index (EASI) and the Investigator Global Assessment Atopic Dermatitis (vIGA-AD) score, as well as the use of rescue therapy.

Participants will be involved in the study for an average of two years, with the possibility of early termination if they experience treatment-related adverse events or serious adverse events. The study involves a series of visits, starting with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be conducted throughout the extended treatment period to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, during which final assessments will be made. The investigational product, APG777, is administered as a solution for injection via subcutaneous injection. Participants are required to use the same non-prescription, non-medicated emollient or moisturizer from the last day of the parent study and throughout the long-term extension study. Conditions that may lead to early termination include non-compliance with the study protocol or the occurrence of significant adverse events.

The clinical trial involves the administration of **APG777**, an investigational medication developed by APOGEE THERAPEUTICS, INC. APG777 is formulated as a **solution for injection** and is administered via **subcutaneous injection**. The active substance, also named APG777, is classified as a protein of other origin. The trial aims to evaluate the long-term safety and tolerability of APG777 in patients with moderate-to-severe **atopic dermatitis**. The dosing schedule and specific dosage amounts are not explicitly detailed in the provided data, but the maximum treatment period is specified as 92 days. Participant compliance with the dosing regimen will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is designed to match the experimental treatment in appearance and administration route, ensuring blinding of both participants and investigators. The pharmaceutical form and specific characteristics of the placebo are not detailed in the provided data. The use of a placebo allows for the assessment of the true efficacy and safety profile of APG777 by providing a baseline for comparison.

The efficacy of APG777 in the treatment of **Atopic Dermatitis** will be assessed through several secondary endpoints. These include the percentage of participants achieving specific improvements in the Eczema Area and Severity Index (EASI) scores, with targets set at EASI 50, 75, 90, and 100, calculated based on the baseline from the Parent Study. Additionally, the percentage of participants achieving a validated Investigator Global Assessment Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction will be evaluated. Another measure of efficacy is the percentage of participants achieving a ≥ 4-point improvement in the weekly mean of the daily Itch Numeric Rating Scale (I-NRS), also based on the Parent Study baseline.

Further assessments will include the percentage of participants who use rescue therapy and those who continue to exhibit EASI 75 and vIGA-AD responses from Week 52 of the Parent Study through the extended treatment period. The percentage of participants maintaining a ≥ 4-point improvement in the I-NRS from Week 52 will also be determined. Serum concentrations of APG777 over time and predose serum concentrations will be measured to support the evaluation of efficacy. These parameters will be collected and analyzed throughout the extended treatment period, averaging two years, with some assessments continuing up to three years.