Inmagene Reports Positive Results of MAD Study on IMG-004, a Daily BTK Inhibitor

Inmagene Biopharmaceuticals, a clinical-stage biotechnology firm specializing in therapies for immunological and inflammatory diseases, has announced encouraging results from the multiple ascending dose (MAD) portion of its Phase 1 clinical trial of IMG-004. This novel Bruton’s tyrosine kinase (BTK) inhibitor is non-covalent, reversible, and capable of penetrating the brain, offering potential new treatment avenues for patients with BTK-mediated immunological conditions.

Previously, a single ascending dose (SAD) study of IMG-004 evaluated doses ranging from 30 to 600 mg in healthy adults. The study found that IMG-004 was well tolerated and possessed a terminal half-life between 26 to 37 hours, providing a robust pharmacodynamic (PD) effect. These promising results led to further exploration through the MAD study.

The Phase 1 MAD trial assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of IMG-004 in 24 healthy adult participants. The study involved administering daily doses of 50 mg, 150 mg, 300 mg, or a placebo for ten days. Findings revealed that IMG-004 was well tolerated at all tested doses, up to 300 mg once daily (QD). There were no severe or serious adverse events (SAEs), and all adverse events (AEs) were deemed unrelated to the study treatment, except for a mild case of constipation. Importantly, no bleeding events were reported.

Liver function, a critical safety metric, was monitored via tests like aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin, all of which remained within normal ranges for all doses. The trial also demonstrated approximately dose-proportional plasma exposure of IMG-004. High-level inhibition, assessed through an ex-vivo basophil inhibition assay, was maintained throughout dosing intervals and sustained for at least 24 hours post-dose for all QD doses.

The study's PD data indicated that all doses provided steady-state exposure achieving at least 90% of the maximal inhibitory concentration (IC90), based on PK/PD modeling. This supports a potential therapeutic dose regimen of 50 mg QD for IMG-004, with a substantial safety margin compared to the well-tolerated 300 mg QD dose.

Yufang Lu, M.D., Ph.D., Chief Medical Officer of Inmagene, expressed satisfaction with the study outcomes, noting that while BTK inhibitors have been validated across nearly ten immunological and inflammatory indications, they often face significant safety issues and inconvenient dosing schedules. The favorable safety profile and robust, lasting inhibition of BTK demonstrated by IMG-004 positions it as a potential best-in-class treatment. The results enable exploration of various QD doses to identify the optimal therapeutic regimen in future trials.

Inmagene's pipeline includes several candidates with best-in-class potential. Leading the efforts is IMG-007, a non-depleting anti-OX40 monoclonal antibody currently in Phase 2a trials for atopic dermatitis and alopecia areata. IMG-004, with its extended half-life and durable PD effect, is ready for Phase 2 development. The company also has IMG-008, a long-acting anti-IL-36R monoclonal antibody, poised to enter Phase 1 clinical trials.

IMG-004, originally discovered by HUTCHMED, is designed for inflammatory and autoimmune diseases that necessitate long-term treatment. It stands out for its potency, selectivity, brain permeability, and potential for daily dosing. The forthcoming evaluations will focus on chronic spontaneous urticaria and hidradenitis suppurativa.