GI-targeted ROCK inhibitor for fibrostenotic Crohn’s disease in phase 1 study

By Liza Laws

- Last updated on GMT

© Getty Images
© Getty Images

Related tags Crohn's disease Drug discovery Drug development Research Data management

Yesterday, (February 28), a clinical-stage biotechnology company, Redx, announced that the first participant has been dosed in a phase 1 clinical trial for RXC008.

The company focuses on discovering and developing small-molecule, targeted therapeutics for the treatment of fibrotic disease and cancer.

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.

Lisa Anson, CEO, of Redx Pharma said: “We are delighted to confirm that the first participant has been dosed in the RXC008 Phase 1 clinical study. RXC008 is a potential first-in-class treatment for patients with fibrostenotic Crohn’s disease, a debilitating condition where successive surgeries are the only treatment option available today.

“This milestone represents the sixth asset from Redx to enter clinical development, continuing our strong track record in small molecule drug discovery as a result of our world-class medicinal chemistry and translational science expertise.”

Significant unmet clinical need

Fibrostenotic Crohn’s disease is a chronic condition that causes inflammation and fibrotic stricture formation in the GI tract. More than 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.

Dr Helen Timmis, interim chief medical officer, of Redx Pharma added: “Fibrostenotic Crohn’s disease patients face a significant unmet clinical need, and I am pleased that we have successfully progressed RXC008 into the clinic.

“The strength of our preclinical package makes us hopeful that RXC008 can be a potential first-in-class therapeutic treatment option for fibrostenotic Crohn’s patients, and we look forward to reporting the phase 1 healthy volunteer data later this year.”

Single and multi-ascending dose

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 a 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.

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