Our GI-targeted ROCK inhibitor is a potential first-in-class clinical candidate designed to treat Crohn’s Disease related fibrosis
Our programme aims to address the high unmet need in the treatment of Crohns’ patients with fibrosis. The current management of fibrotic strictures of the gastrointestinal (GI) tract is primarily surgical as there are no drugs approved that target this fibrosis and the disease progresses despite intervention with anti-inflammatory therapies.
ROCK1 and ROCK2 are intracellular kinases with multiple functions, shown to be implicated at various points in pathways leading to fibrosis. However, systemic ROCK1/2 inhibitors (or pan-ROCK inhibitors) are known to induce hypotension and are therefore unlikely to be tolerated by patients. Our GI-targeted ROCK inhibitor is designed to only work at the site of action in the gastrointestinal tract and to degrade quickly, once absorbed into the bloodstream, through enzyme-mediated metabolism.
Our GI-targeted ROCK inhibitor shows both prophylactic and therapeutic effects on fibrosis in multiple animal models. Our inhibitor is designed to reduce fibrosis, prevent disease progression and surgical intervention thereby improving patients’ lives.
Reduction in collagen in a murine model of Crohn’s fibrosis
Increase of collagen staining shown in blue in the DSS treated animals. GI-targeted ROCK inhibitor reduces production of collagen seen as a reduction in blue (trichrome) staining.