Apogee Therapeutics has announced encouraging interim Phase 1 data for APG777, a novel subcutaneous monoclonal antibody targeting interleukin-13 (IL-13) for the treatment of moderate-to-severe atopic dermatitis and other inflammatory diseases. The findings exceeded the company's trial objectives ahead of the planned schedule, demonstrating a remarkable half-life of approximately 75 days across all doses tested.
Extended Half-Life Enables Sustained Treatment
The Phase 1 trial, a first-in-human, randomized, double-blind, placebo-controlled study, evaluated the safety and pharmacokinetics of APG777 in 40 healthy volunteers across three single-ascending dose and two multiple-ascending dose cohorts. Results showed deep and sustained inhibition of key atopic dermatitis biomarkers for up to three months, with single doses up to 1,200mg and multiple doses of 300mg being well-tolerated.
"We are thrilled by the positive PK, PD, and safety findings from our Phase 1 trial," said Michael Henderson, MD, chief executive officer of Apogee. "These results underscore the promising potential of APG777 to offer patients a transformational therapy that could drive improved clinical responses and extend dosing intervals."
Safety Profile and Adverse Events
The trial demonstrated a favorable safety profile, with the most common treatment-emergent adverse events including vascular access site pain and headache. Notably, no Grade 3 treatment-emergent adverse events or severe adverse events were observed during the study period.
Addressing Unmet Medical Need
Atopic dermatitis affects approximately 40 million adults and 18 million children in the United States, France, Germany, Italy, Japan, Spain and the United Kingdom, with 40 percent having moderate-to-severe disease. Jonathan Silverberg, MD, PhD, MPH, professor of dermatology at The George Washington University School of Medicine and Health Sciences, emphasized the clinical significance of the extended dosing potential.
"Currently approved therapies for atopic dermatitis and other immunology indications typically call for injections every two to four weeks, which can lead to poor treatment adherence and long-term disease control," said Silverberg. "I am very encouraged by the initial data from this study, which demonstrate the potential for APG777 as a well-tolerated treatment with a half-life that would support less frequent injections."
Phase 2 Development Plans
The upcoming Phase 2 trial is planned for initiation in the first half of 2024, structured as a 16-week study that will enroll approximately 110 patients in part A. The primary endpoint will focus on average percentage changes in Eczema Area and Severity Index score from baseline to week 16. Following part A, part B will encompass a dose optimization phase with approximately 360 patients randomized to high, medium, or low dose APG777 versus placebo.
Preclinical Comparisons and Pipeline Expansion
In head-to-head preclinical studies, APG777 showed equivalent or better potency to lebrikizumab in the inhibition of IL-13 signaling. The company plans to initiate a Phase 2 trial in asthma in 2025 and explore opportunities for development in additional indications including alopecia areata, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria, eosinophilic esophagitis, and prurigo nodularis.
Apogee's pipeline also includes three other half-life extended drugs: APG808 for chronic obstructive pulmonary disease, APG990 for atopic dermatitis, and APG222 for atopic dermatitis. The company is developing APG279, designed to address multiple immune signaling intervention points through dual inhibition of IL-13 and OX40L, which could provide a potential first-in-class combination treatment.
