RXC008 (GI-restricted pan-ROCK inhibitor)
Potential first-in-class treatment for fibrostenotic Crohn’s disease
Programme summary
Phase 2 study preparations ongoing, IND open with dosing in fibrostenotic Crohn’s patients to commence during H2 2026
Crohn’s disease affects 1.7m1 people globally and >70,000 new cases are diagnosed each year. More than 50% of patients2 with Crohn’s disease can develop significant fibrosis and stricture formation within ten years after diagnosis; this is known as fibrostenotic Crohn’s disease.
The current management of fibrotic strictures of the gastrointestinal tract is primarily surgical as no drugs are specifically approved for fibrosis, which can progress despite intervention with effective anti-inflammatory therapies.
The current management of fibrotic strictures of the gastrointestinal tract is primarily surgical as no drugs are specifically approved for fibrosis, which can progress despite intervention with effective anti-inflammatory therapies.
Relapse rate post-surgical intervention is high with >50% patients requiring further surgery within 10 years, many within 12 months.2 Consequently, patients suffer progressive loss of gastrointestinal function and repeated resections can lead to major health complications such as short bowel syndrome.
It is therefore particularly exciting that in preclinical studies, RXC008 has shown strong anti-fibrotic therapeutic effects in multiple animal models of inflammatory bowel disease, including full reversal back to baseline in a therapeutic 12-week DSS model with a pharmacologically identical tool compound (Figure 1).
RXC008, is a GI-restricted pan-ROCK inhibitor designed to work specifically at the site of fibrosis in the gastrointestinal tract and is GI-restricted through three separate mechanisms, firstly it is restricted to the gut via low permeability and high efflux, it is then designed to degrade quickly, if absorbed into the bloodstream, through enzyme-mediated metabolism, and finally, if required, can be rapidly cleared by the liver. This GI-restriction avoids the hypotensive side effects caused by systemic pan-ROCK inhibition that have, to date, limited the development of pan-ROCK inhibitors (figure 2).
RXC008 has an open IND and was granted US FDA Fast Track designation in January 2026. Following a successful Phase 1 healthy volunteer study, RXC008 will commence a Phase 2 clinical study in fibrostenotic Crohn’s patients in H2 2026.
Phase 1 healthy volunteer clinical study showed good tolerability, tissue exposure and safety profile. Data presented at the European Crohn’s and Colitis Organisation and Digestive Disease Week conferences in 2025
In the Phase 1 study (figure 3), RXC008 was well tolerated (up to 1000mg as a single oral dose and up to 300mg dosed daily over 14 days). There were no adverse events (AEs) reported in the single ascending dose (SAD) study. In the multiple ascending dose (MAD) study, all AEs were mild or moderate with no trends observed. There were no serious adverse events and no AEs leading to treatment discontinuation. Importantly, no hypotension or tachycardia (known liabilities of systemic pan-ROCK inhibition) were observed in any participant. Robust data was generated during the study that confirmed the drug to be gut restricted. Negligible systemic exposure was observed at daily RXC008 doses up to 300mg; high concentrations of RXC008 were found in mucosal biopsy samples obtained from healthy participants via ileocolonoscopy at Day 14 during the MAD section of the trial. The study also confirmed a potential target engagement marker that can be taken forward into the clinic.
Phase 2 study in fibrostenotic Crohn’s patients to commence during H2 2026. For further information please contact: c.tilston@redxtherapeutics.com
References
- Clarivate, Crohn’s disease landscape & forecast pg 39, Published Sep 2022
- Chan WPW, et al. J Gastroenterol Hepatol. 2018 May;33(5):998-1008.
- Julian L, Olson MF. Small GTPases. 2014;5:e29846. Epub 2014 Jul 10.
- Rieder F, et al. Nat Rev Drug Discov. 2025 Jul;24(7):543-569.
- Noma et al 2006: Am J Physiol Cell Physiol. 2006 Mar;290(3):C661‐8. 3.
Phase 2 study preparations ongoing, IND open with dosing in fibrostenotic Crohn’s patients to commence during H2 2026
Crohn’s disease affects 1.7m1 people globally and >70,000 new cases are diagnosed each year. More than 50% of patients2 with Crohn’s disease can develop significant fibrosis and stricture formation within ten years after diagnosis; this is known as fibrostenotic Crohn’s disease.
The current management of fibrotic strictures of the gastrointestinal tract is primarily surgical as no drugs are specifically approved for fibrosis, which can progress despite intervention with effective anti-inflammatory therapies.
The current management of fibrotic strictures of the gastrointestinal tract is primarily surgical as no drugs are specifically approved for fibrosis, which can progress despite intervention with effective anti-inflammatory therapies.
Relapse rate post-surgical intervention is high with >50% patients requiring further surgery within 10 years, many within 12 months.2 Consequently, patients suffer progressive loss of gastrointestinal function and repeated resections can lead to major health complications such as short bowel syndrome.
It is therefore particularly exciting that in preclinical studies, RXC008 has shown strong anti-fibrotic therapeutic effects in multiple animal models of inflammatory bowel disease, including full reversal back to baseline in a therapeutic 12-week DSS model with a pharmacologically identical tool compound (Figure 1).
RXC008, is a GI-restricted pan-ROCK inhibitor designed to work specifically at the site of fibrosis in the gastrointestinal tract and is GI-restricted through three separate mechanisms, firstly it is restricted to the gut via low permeability and high efflux, it is then designed to degrade quickly, if absorbed into the bloodstream, through enzyme-mediated metabolism, and finally, if required, can be rapidly cleared by the liver. This GI-restriction avoids the hypotensive side effects caused by systemic pan-ROCK inhibition that have, to date, limited the development of pan-ROCK inhibitors (figure 2).
RXC008 has an open IND and was granted US FDA Fast Track designation in January 2026. Following a successful Phase 1 healthy volunteer study, RXC008 will commence a Phase 2 clinical study in fibrostenotic Crohn’s patients in H2 2026.
Phase 1 healthy volunteer clinical study showed good tolerability, tissue exposure and safety profile. Data presented at the European Crohn’s and Colitis Organisation and Digestive Disease Week conferences in 2025
In the Phase 1 study (figure 3), RXC008 was well tolerated (up to 1000mg as a single oral dose and up to 300mg dosed daily over 14 days). There were no adverse events (AEs) reported in the single ascending dose (SAD) study. In the multiple ascending dose (MAD) study, all AEs were mild or moderate with no trends observed. There were no serious adverse events and no AEs leading to treatment discontinuation. Importantly, no hypotension or tachycardia (known liabilities of systemic pan-ROCK inhibition) were observed in any participant. Robust data was generated during the study that confirmed the drug to be gut restricted. Negligible systemic exposure was observed at daily RXC008 doses up to 300mg; high concentrations of RXC008 were found in mucosal biopsy samples obtained from healthy participants via ileocolonoscopy at Day 14 during the MAD section of the trial. The study also confirmed a potential target engagement marker that can be taken forward into the clinic.
Phase 2 study in fibrostenotic Crohn’s patients to commence during H2 2026. For further information please contact: c.tilston@redxtherapeutics.com
References
- Clarivate, Crohn’s disease landscape & forecast pg 39, Published Sep 2022
- Chan WPW, et al. J Gastroenterol Hepatol. 2018 May;33(5):998-1008.
- Julian L, Olson MF. Small GTPases. 2014;5:e29846. Epub 2014 Jul 10.
- Rieder F, et al. Nat Rev Drug Discov. 2025 Jul;24(7):543-569.
- Noma et al 2006: Am J Physiol Cell Physiol. 2006 Mar;290(3):C661‐8. 3.
