Apogee Therapeutics, a clinical-stage biotechnology company, has announced significant progress in the development of APG777, a novel biologic for the treatment of moderate-to-severe atopic dermatitis (AD). The first patient has been dosed in Part B of the Phase 2 APEX clinical trial, and enrollment for Part A has been completed ahead of schedule.
APEX Trial Design and Enrollment
The APEX trial is a Phase 2 randomized, placebo-controlled study evaluating APG777, a subcutaneous extended half-life monoclonal antibody targeting IL-13, a key cytokine in inflammation and a primary driver of AD. The trial combines the typical Phase 2a and 2b portions into a single protocol. Part A exceeded the expected enrollment with 123 patients randomized 2:1 to APG777 versus placebo. Patients receiving APG777 were administered an induction regimen of 720mg at weeks 0 and 2, followed by 360mg at weeks 4 and 12. Part B is a placebo-controlled dose optimization study with approximately 280 patients randomized 1:1:1:1 to high, medium, or low dose APG777 versus placebo.
The primary endpoint for both parts of the study is the mean percentage change in EASI (Eczema Area and Severity Index) score from baseline at week 16. Secondary endpoints include EASI-75 (75% improvement in EASI score) and IGA (Investigator's Global Assessment) 0/1 at week 16.
Potential for Improved Dosing and Efficacy
Carl Dambkowski, M.D., Chief Medical Officer of Apogee, stated that positive results from the Phase 1 healthy volunteer trial enabled the design of the Phase 2 trial, where APG777 is modeled to exceed lebrikizumab exposures by approximately 30-40% with potential for improved clinical responses. He also noted that APG777 could reduce the number of injections during induction by about half and in maintenance by approximately 70-90% compared to currently available therapies.
APG777: A Novel IL-13 Inhibitor
APG777 is designed to address the limitations of existing therapies through advanced antibody engineering, optimizing its half-life and other properties. Phase 1 trial data showed a half-life of 77 days, with near-complete inhibition of pSTAT6 (a key signaling molecule in the IL-13 pathway) for up to 12 months after a single administration, along with sustained TARC (Thymus and Activation-Regulated Chemokine) inhibition.
Future Development Plans
Apogee plans to advance the development of APG777 into other indications, including initiating a Phase 1b trial in asthma in the first half of 2025, followed by a Phase 2b trial in asthma in the second half of 2025, and launching a Phase 2 trial in eosinophilic esophagitis (EoE) in 2026. Additionally, Apogee is exploring combination therapies, including a Phase 1b trial of APG777 and APG990 (targeting OX40L) in 2025, with data expected in the second half of 2026. This combination study aims to evaluate safety, pharmacokinetics, pharmacodynamics, and efficacy against dupilumab in patients with moderate-to-severe AD.
R&D Day Highlights
At its virtual R&D Day, Apogee shared positive updates on its pipeline, including APG808, which showed a 55-day half-life in Phase 1 data, supporting a potential 2-3 month dosing interval. The company also presented preclinical proof-of-concept data for APG777 in combination with APG990 and APG333 for atopic dermatitis, asthma, and COPD.
Topline data from Part A of the APG777 Phase 2 trial is anticipated in mid-2025, with maintenance data expected in the first half of 2026, and Part B data in the second half of 2026.
