Inmagene Biopharmaceuticals has announced positive topline results from its Phase 2a clinical trial evaluating IMG-007 for the treatment of moderate-to-severe atopic dermatitis. The study demonstrated a significant reduction in disease severity, with a mean reduction of 77% in the Eczema Area and Severity Index (EASI) score after just four weeks of treatment. These findings, along with data from a Phase 1 trial of the subcutaneous formulation, suggest that IMG-007 could offer a novel approach to managing this chronic skin condition.
Phase 2a Trial Results
The Phase 2a open-label study (NCT05984784) enrolled 13 adult patients with atopic dermatitis across sites in Canada and the US. Participants received three doses of intravenous IMG-007 at weeks 0, 2, and 4. By week 16, the mean percent change in EASI score was 77%, and the EASI-75 response rate (percentage of patients achieving at least a 75% reduction in EASI score) was 54%. These results are particularly noteworthy as they align with efficacy demonstrated by other OX40/OX40L-targeting monoclonal antibodies (mAbs) that typically require longer treatment durations.
"The positive topline results from the Phase 2a trial of IMG-007 in patients with atopic dermatitis are exciting," said Yufang Lu, MD, PhD, Inmagene’s chief medical officer. "The robust observed clinical activity and biomarker data that resulted from a short 4-week treatment, as well as the well-tolerated safety profile, suggest that the ADCC silencing of IMG-007 has retained desired biological activity of OX40 blockade while improving the tolerability."
Durable Inflammatory Marker Inhibition
In addition to clinical improvements, the trial also revealed durable inhibition of serum inflammatory markers associated with various T helper (Th) cell subsets, including Th1, Th2, and Th17 cells. This inhibition persisted for up to 24 weeks following treatment, indicating a sustained effect on the underlying immune dysregulation in atopic dermatitis.
Safety and Tolerability
Importantly, IMG-007 demonstrated a favorable safety profile in the Phase 2a trial. There were no adverse events leading to treatment discontinuation, no serious adverse events reported, and no treatment-related adverse events such as pyrexia or chills.
Subcutaneous Formulation Shows Promise
Inmagene also presented data from a Phase 1 trial (NCT06304740) evaluating the pharmacokinetics and safety of a subcutaneous formulation of IMG-007 in 16 healthy adult subjects. The subcutaneous formulation exhibited a pharmacokinetic profile consistent with the intravenous formulation. A single subcutaneous dose of IMG-007 demonstrated a mean terminal half-life of 34.7 days, which is considerably longer than other OX40/OX40L mAbs currently in clinical development.
The subcutaneous formulation was also well-tolerated, with injection site reactions being the most commonly reported adverse events. Notably, these reactions were more frequent in the placebo arm (75%) compared to the IMG-007 arm (25%).
Implications for Atopic Dermatitis Treatment
Atopic dermatitis is a chronic, relapsing disease that often requires long-term management. Current biologic therapies typically require frequent injections every 2 to 4 weeks. The extended half-life of the subcutaneous IMG-007 formulation, coupled with its favorable tolerability profile, could potentially allow for less frequent dosing regimens, offering a significant advantage for patients.
"Atopic dermatitis is a chronic relapsing disease that requires long-term management, and currently approved biologics require frequent injections, every 2 or 4 weeks," Lu added. "The extended half-life of IMG-007 [subcutaneous] formulation coupled with a favorable tolerability profile would potentially allow for IMG-007 to provide differentiated dosing regimens in the long-term treatment of atopic dermatitis."
