Redx announced that the first participant has been dosed in a Phase 1 clinical trial for RXC008. RXC008 is a wholly-owned gastro-intestinal (GI) targeted Rho Associated Coiled-Coil Containing Protein Kinase (ROCK) inhibitor, being developed as a potential first-in-class treatment for patients with fibrostenotic Crohn's disease. The primary objective of this first-in-human study is to evaluate the safety and pharmacokinetic (PK) profile of the drug and it is expected that results from the healthy volunteer cohorts will be available by the end of 2024.

Fibrostenotic Crohn's disease is a chronic condition that causes inflammation and fibrotic stricture formation in the GI-tract. Over 50% of patients diagnosed with Crohn's disease will develop fibrostenosis within 10 years of diagnosis. There are currently no drugs specifically approved for the underlying fibrosis, which can progress despite intervention with anti-inflammatory therapies.

The only current treatment options are invasive surgical procedures to remove the affected part of the GI-tract with the majority of patients requiring many successive surgical interventions. The Phase 1 clinical study consists of two parts. The first in healthy volunteers includes both single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, the latter being dosed for 14 days.

The primary endpoint for the healthy volunteer cohorts will be safety, with secondary endpoints being related to RXC008's PK profile. The second part of the study will investigate patients with fibrostenotic Crohn's disease who will be dosed for a one-month duration with a placebo control, to show safety along with PK profile, target engagement and changes in circulating biomarkers. Data from the healthy volunteer cohorts are expected to be available by the end of 2024.

RXC008 is a potent, oral, small molecule non-systemic ROCK 1/2 inhibitor that avoids the significant cardiovascular side effects of pan-ROCK inhibitors, including tachycardia and hypotension, by being restricted to the GI-tract via high efflux and low permeability. This results in virtually no systemic breakthrough, with the molecule being rapidly metabolised by paraoxonase enzymes in the plasma should any breakthrough occur under particular circumstances. RXC008 has a strong preclinical package across multiple therapeutic models, data from which was presented at the 2022 Inflammatory Bowel Disease (IBD) Nordic Conference, including results from a therapeutic 12-week DSS model with a closely related GI-targeted ROCK inhibitor, REDX08087.

In this model Redx was able to show complete reversal of preformed GI-fibrosis as measured by trichome collagen staining, fully reversing fibrosis back to baseline levels. This level of anti-fibrotic effect is the strongest seen in any of Redx's fibrosis models and modes of action to date. RXC008 is being developed to be used in conjunction with anti-inflammatories and other symptomatic treatments for Crohn's to address the underlying fibrosis of the disease.