Inmagene Announces Favorable Topline Efficacy and Safety Results for IMG-007 in Atopic Dermatitis

Treatment with IMG-007, a nondepleting anti-OX40 monoclonal antibody, resulted in significant clinical improvements in adults with moderate-to-severe atopic dermatitis (AD), according to Phase 2a trial results announced by Inmagene Biopharmaceuticals on January 9, 2025.1

The open-label phase 2a trial demonstrated that IMG-007, administered via intravenous (IV) infusion at weeks 0, 2, and 4, led to a mean reduction in Eczema Area and Severity Index (EASI) of 77% as early as week 4; 54% of participants achieved an EASI-75 response at week 16, according to the Inmagene announcement. The findings are within the range seen with other investigational OX40/OX40L-targeting mAbs with longer treatment duration (at least 16 weeks).1

These clinical benefits were associated with durable suppression of inflammatory markers up to week 24, highlighting IMG-007’s ability to modulate T helper cell (Th1, Th2, and Th17) pathways.1

The findings also underscore the potential for extended dosing intervals due to the agent’s prolonged half-life. “IMG-007 is the only clinical-stage monoclonal antibody targeting OX40/OX40L signaling in both blood and tissue without depleting T cells,” Jonathan Wang, founder and CEO of Inmagene, said in the press release. The “extended half-life combined with the sustained efficacy demonstrated will enable us to explore long dosing intervals, such as every 24 weeks, for maintenance therapy in AD and other potential indications.”1

The “extended half-life combined with the sustained efficacy demonstrated will enable us to explore long dosing intervals, such as every 24 weeks, for maintenance therapy in AD and other potential indications.”

The trial enrolled 13 adults with moderate-to-severe AD across sites in the US and Canada to evaluate IMG-007 safety, pharmacokinetics (PK), and efficacy. IMG-007 was well-tolerated, with no serious adverse events (SAEs), treatment-related AEs, or AEs leading to discontinuation of treatment, according to Inmagene. Notably, no participants reported pyrexia or chills, adverse effects often associated with monoclonal antibody therapies.1 The current findings, the company said, are similar to interim results reported in May 2024.2

“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 [antibody-dependent cellular cytotoxicity (ADCC)] silencing of IMG-007 has retained desired biological activity of OX40 blockade while improving the tolerability,” Inmagene chief medical officer Yufang Lu, MD, PhD, said in the release.

Biologic agents currently approved to manage AD require injections every 2 to 4 weeks, a treatment burden for individuals with the chronic relapsing disease that requires long-term management, Lu observed. “The extended half-life of IMG-007 SC formulation coupled with a favorable tolerability profile would potentially allow for IMG-007 to provide differentiated dosing regimens in the long-term treatment of AD.”

Evaluation of SC Formulation

In a separate phase 1 study (NCT06304740), Inmagene evaluated the safety and PK of a subcutaneous (SC) formulation of IMG-007. In this study of 16 healthy adults, the SC formulation demonstrated a PK profile consistent with that of the IV formulation, with a half-life of approximately 35 days, a period substantially longer that that seen with other investigational OX40/OX40L mAbs, according to the company. Serum concentrations remained above the therapeutic threshold for OX40/OX40L inhibition for up to 18 weeks following a single dose.

The SC formulation was generally well-tolerated, with injection site reactions (eg, injection site pain, erythema, and pruritus) being mild and more frequent in the placebo group (75%) than the IMG-007 group (25%). The company plans to initiate a phase 2b dose-finding study with the SC formulation in adults with moderate-to-severe AD in the first quarter of 2025.

IMG-007 is a humanized non-depleting anti-OX40 IgG1 mAb with a silenced ADCC function and an extended half-life. The OX40-OX40L axis plays a significant role in T cell activation, proliferation, and survival and so figures prominently in the pathogenesis of inflammatory and immunologic disease. By silencing function, the therapy minimizes the potential for immune-mediated adverse effects while preserving efficacy, according to Inmagene.

References

1. Inmagene reports positive topline results of IMG-007, a nondepleting anti-OX40 monoclonal anntibody with an extended half life, for the treatment of atopic dermatitis. News release. January 9, 2025. Accessed January 9, 2025. https://www.morningstar.com/news/globe-newswire/9328816/inmagene-reports-positive-topline-results-of-img-007-a-nondepleting-anti-ox40-monoclonal-antibody-with-an-extended-half-life-for-the-treatment-of-atopic-dermatitis
2. Inmagene reports positive interim results from phase 2a trial of IMG-007, a nondepleting anti-OX40 monoclonal antibody with an extended half life, for the treatment of atopic dermatitis. News release. May 6, 2024. Accessed January 9, 2025. https://inmagenebio.com/press-release/inmagene-reports-positive-interim-results-from-phase-2a-trial-of-img-007-a-nondepleting-anti-ox40-monoclonal-antibody-with-an-extended-half-life-for-the-treatment-of-atopic-dermatitis/