Treatment with Inmagene Biopharmaceuticals’ anti-OX40 monoclonal antibodyled to “rapid, marked, and durable” improvements of skin signs in in a Phase 2a trial of patients with atopic dermatitis (AD)
IMG-007 is a non-depleting anti-OX40 mAb, bioengineered to have a silenced antibody-dependent cellular cytotoxicity (ADCC) function and a prolonged half-life.
The Phase 2a trial (NCT05984784) evaluates the safety, pharmacokinetics, and efficacy of IMG-007 in adult patients with moderate-to-severe AD who had inadequate response to and/or intolerant of topical therapies. Patients who had received prior systemic agents, such as biologics, were also included in the trial. Topical or systemic AD medications were not permitted during the study. Eligible patients received three intravenous infusions of 300mg IMG-007 over 4 weeks (Baseline, Week 2 and 4) and were followed up for up to 24 weeks. Key study endpoints include safety and percent change from baseline in eczema area and severity index (EASI) over time.
A total of 13 patients were enrolled from 6 centers in the U.S. and Canada. Baseline key disease characteristics included mean EASI of 29.5, mean body surface area (BSA) of 52.0%, and 61.5% patients with investigator’s global assessment (IGA=3) and 38.5% with IGA=4.
IMG-007 treatment resulted in a rapid and marked improvement from baseline in EASI score as early as Week 1 and continued improvement over time after the last dose of IMG-007 at Week 4, the study showed. The mean percent improvement from baseline in EASI was 23%, 29%, 47%, 66%, 68%,77%, and 87% at Weeks 1, 2, 4, 8, 12, 16, and 20, respectively.
By Week 20, a total of 69%, 54%, and 31% of patients achieved EASI improvement of at least 50% (EASI-50), at least 75% (EASI-75), and at least 90% (EASI-90), respectively.
There were no serious adverse events (SAEs), and no adverse events (AEs) leading to treatment discontinuation, and no treatment-related AEs. There were no reports of pyrexia or chills.
Final results are anticipated in Q3 2024.
“Inhibiting OX40-OX40L signaling is an exciting potential therapeutic approach to treating AD,” says The Dermatology Digest Editorial Advisory Board Member Jonathan Silverberg, MD, PhD, Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC. “By uniquely targeting the OX40 receptor without depleting T cells and with its long half-life, IMG-007 presents a best-in-class potential to not only minimize safety risks associated with T cell depletion, but also provide patients with a more convenient dosing regimen such as Q12W.”
“We are highly encouraged by the remarkable efficacy seen with a short 4-week treatment period. Future studies of continuous treatment with IMG-007 in patients with AD could potentially drive more robust efficacy than seen in this proof-of-concept study,” adds Yufang Lu, MD, PhD, Chief Medical Officer of Inmagene. “Given the important role of the OX40-OX40L axis in the pathogenesis of a spectrum of I&I diseases, IMG-007 could be suitable for a number of indications. We are working hard to accelerate the clinical development of IMG-007 in AD with our subcutaneous formulation.”
In a prior Phase 1 single-dose study in healthy adults, IMG-007 demonstrated a favorable safety and tolerability profile, with no reports of pyrexia or chills, which is consistent with the abolished ADCC function. Furthermore, IMG-007 showed a slow antibody clearance and a 31-day half-life at anticipated therapeutic dose levels, which could enable it to be dosed every 12 weeks (Q12W) for induction therapy, and even less frequently for maintenance therapy in AD treatment.
In addition to the Phase 2a trial in patients with AD for which final results are anticipated in Q3 2024, IMG-007 is also being evaluated in a global study in adult patients with alopecia areata with anticipated initial data readout in Q4 2024.
