Trial of novel autoimmune disease treatment ICP-538 launches in China
First healthy volunteer dosed in study testing oral therapy for MS, other conditions
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A doctor and a patient look at a tablet while talking in an exam room. (Photo from iStock)
- A trial testing ICP-538, a novel oral therapy for multiple sclerosis and other autoimmune diseases, has launched in China.
- Developer Innocare Pharma said the first healthy volunteer in the study has been dosed with the medication.
- Along with MS, ICP-538 aims to treat conditions like inflammatory bowel disease and lupus.
Innocare Pharma has dosed the first healthy volunteer in a clinical trial in China testing ICP-538, its oral treatment candidate for multiple sclerosis (MS) and other autoimmune diseases.
The novel experimental therapy works by promoting the degradation of the VAV1 protein, essential for the function of T-cells and B-cells, which are immune cells that play important roles in driving autoimmune conditions. It is the first VAV1 degrader approved to enter clinical trials in China and the second worldwide, according to the developer.
“We are pleased to see that we have rapidly advanced clinical development, and we believe that ICP-538 will become a better treatment option for patients with autoimmune diseases,” Jasmine Cui, cofounder, chairwoman, and CEO of Innocare, said in a company press release announcing the trial’s launch.
Autoimmune diseases are conditions in which the immune system mistakenly attacks the body’s own cells and tissues. In MS, this immune attack targets the myelin sheath, a protective coating around nerve fibers that is essential for the transmission of nerve signals.
In MS and many other autoimmune diseases, inflammatory attacks are mainly mediated by two immune cell types, called B-cells and T-cells.
ICP-538 works as molecular glue connecting target proteins
ICP-538 is an oral molecular glue degrader (MGD) designed to promote the rapid degradation of the VAV1 protein. This is expected to lessen the activity of these immune cells and reduce inflammatory damage.
As the acronym MGD suggests, the therapy works as a molecular glue that connects the target protein to another protein — one called CRBN E3 ubiquitin ligase, which is involved in natural protein degradation mechanisms.
Preclinical studies have shown that ICP-538 causes a rapid and deep degradation of VAV1, and its effects are dose-dependent, meaning that higher drug levels result in greater VAV1 degradation. It also significantly reduced the production of proinflammatory molecules associated with immune-mediated diseases, with no detectable effects on other proteins.
“As a novel therapy, the VAV1 molecular glue degrader offers three major advantages: high target selectivity, mediation of multiple mechanisms of action, and high efficacy,” Cui said.
In addition to MS, Innocare is developing ICP-538 for autoimmune conditions such as inflammatory bowel disease and systemic lupus erythematosus.
Another VAV1 degrader, called MRT-6160, is also being developed for MS and other autoimmune conditions, and has already been tested in a U.S. Phase 1 trial involving healthy volunteers.
