Inmagene Announces Positive Topline Results of a Multiple Ascending Dose Study of  a Non-Covalent Reversible BTK Inhibitor With Once- Daily Dosing Potential

Inmagene Biopharmaceuticals recently announced positive topline results from the multiple ascending dose (MAD) portion of its randomized, double-blind, placebo-controlled Phase 1 study of IMG-004, a potent, non-covalent, reversible, and brain permeable Bruton’s tyrosine kinase (BTK) inhibitor.

In a prior Phase 1 single ascending dose (SAD) study of 30 to 600 mg in healthy adults, IMG-004 was well-tolerated and exhibited a terminal half-life ranging from 26 to 37 hours and robust PD effect, which supported further exploration of IMG-004 QD dose regimens.

The Phase 1 MAD study evaluated the safety, PK, and PD of IMG-004 in 24 healthy adults. Participants received IMG-004 50 mg, 150 mg, 300 mg or placebo QD for 10 days. The study showed that doses of up to 300 mg IMG-004 QD were well tolerated. No severe or serious adverse events (SAEs) were reported. All adverse events (AEs) were judged as unrelated to the study treatment except for one mild AE of constipation. There were no reports of bleeding events. Additionally, key liver function tests, including aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin, remained within the normal reference ranges for all tested QD doses.

Plasma exposure of IMG-004 was approximately dose proportional. Pharmacodynamic assessment, using an ex-vivo basophil inhibition assay, demonstrated that high-level inhibition was achieved throughout the dosing intervals and was sustained for at least 24 hours post dose in all QD doses.

All three doses tested in this study provided a steady-state exposure over the entire dosing interval which achieved at least 90% maximal inhibitory concentration (IC90), estimated based on PK/PD modeling. Taken together, the data supports a potential therapeutic dose regimen of 50 mg QD for IMG-004, with a wide safety margin relative to the highest tested 300 mg QD dose that was well-tolerated.

“We are very pleased with the results of this study. BTK inhibitors have been clinically validated in nearly ten I&I indications to date. The class, however, has been limited by significant safety concerns and inconvenient dosing regimens,” said Yufang Lu, MD, PhD, Chief Medical Officer of Inmagene. “The robust and durable BTK inhibition and favorable safety profile that IMG-004 demonstrated in this study support its potential as best-in-class and allows to explore a wide range of QD doses to identify an optimal dose regimen in future trials.”

IMG-004 is a non-covalent, reversible small molecule inhibitor targeting BTK. Designed specifically for inflammatory and autoimmune diseases that usually require long-term treatment, IMG-004 is potent, highly selective and brain permeable. In a single ascending dose (SAD) study of IMG-004 in healthy adults, IMG-004 exhibited a half-life of 26-37 hours, which is longer than most leading BTK inhibitors. Additionally, its sustained pharmacodynamic effect has enabled the potential for once daily dosing. IMG-004 is planned to be initially evaluated for the treatment of chronic spontaneous urticaria and hidradenitis suppurativa. IMG-004 was originally discovered by HUTCHMED, with Inmagene assuming the development responsibility at the candidate stage.

Inmagene is a global clinical-stage biotechnology company developing novel therapeutics for immunological and inflammatory (I&I) diseases. The company’s highly differentiated clinical-stage pipeline has multiple candidates with best-in-class potential. The lead asset IMG-007, a nondepleting anti-OX40 mAb, is in two global Phase 2a clinical trials in atopic dermatitis and alopecia areata. IMG-004, a non-covalent reversible BTK inhibitor with an extended half-life and durable pharmacodynamic effect, enabling its potential for once-daily dosing and is ready for Phase 2 development. IMG-008, a long-acting anti-IL-36R mAb is entering global Phase 1 clinical development. For more information, visit www.inmagenebio.com.