Healthy Volunteers Dosed in Trial of Therapy Candidate IMG-004

The first healthy volunteer in the U.S. has been dosed in a Phase 1 clinical trial evaluating IMG-004, an oral inhibitor of Bruton’s tyrosine kinase (BTK) being developed as a potential therapy for a wide range of inflammatory and autoimmune diseases, including ankylosing spondylitis (AS).

In the Phase 1 study (NCT05349097), which aims to enroll 74 healthy adults (ages 18–60), participants will be assigned randomly to single and multiple ascending doses of IMG-004 or a placebo.

The trial intends to assess IMG-004’s safety, tolerability, pharmacokinetics, and pharmacodynamics. Pharmacokinetics refers to the movement of a medicine into, through, and out of the body, while pharmacodynamics is defined as the effects of a compound on the body. The trial is expected to be completed in July 2023.

IMG-004, discovered by Hutchmed and co-developed jointly with Inmagene, is an oral, third-generation reversible inhibitor of BTK, which is vital for the development and functioning of several immune cells. By inhibiting BTK, IMG-004 may help thwart inflammatory responses.

According to Inmagene, IMG-004 is able to penetrate the blood-brain barrier — a hard-to-reach semipermeable border that protects the brain against toxins in the blood, but also blocks potential treatments. IMG-004 has shown a higher potency and lower safety risks compared to current investigational BTK inhibitors, including Genentech’s fenebrutinib and Sanofi’s rilzabrutinib.

“IMG-004 was designed specifically for inflammatory and autoimmune diseases, and in preclinical models, it has shown improved activity, selectivity, and pharmacokinetic profile,” Jean-Louis Saillot, MD, chief development officer of Inmagene, said in a press release.

“We welcome the start of the IMG-004 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with immunological diseases,” he added.

“IMG-004 is the second novel drug candidate under the collaboration with Hutchmed which Inmagene has successfully advanced into clinical studies this year,” said Jonathan Wang, PhD, Inmagene’s chairman and CEO.

The companies previously collaborated in the development of IMG-007, an investigational monoclonal antibody targeting the OX40 receptor, a protein involved in activation of certain immune cells.

Inmagene’s most advanced candidate therapy, IMG-020 (also known as izokibep), is designed to inhibit the signaling mediated by interleukin (IL)-17A, a known player in ankylosing spondylitis. Currently approved IL-17A inhibitors for AS in the U.S. and elsewhere include Cosentyx (secukinumab) and Taltz (ixekizumab).

According to the press release, the company intends to initiate Phase 2 studies testing IMG-020 in AS, as well as psoriatic arthritis and uveitis.