Redx Pharma has announced preclinical efficacy data in immune mediated models for RXC007.
The data on RXC007, its lead fibrosis asset, was presented alongside encouraging final phase 1 safety and pharmacokinetic data at the International Colloquium on Lung and Airway Fibrosis (ICLAF) on October 2 by Nicolas Guisot, research fellow at Redx Pharma.
The data presented showed the pleiotropic, anti-fibrotic effects of RXC007, an orally bioavailable selective ROCK2 (Rho-Associated Protein Kinase 2) inhibitor in murine bleomycin-induced lung fibrosis and in murine sclerodermatous chronic graft versus host disease (GvHD) models.
The murine sclerodermatous cGvHD model recapitulates aspects of human scleroderma with prominent skin thickening, lung fibrosis, and upregulation of cutaneous collagen. Furthermore, the underlying disease mechanisms that drive pathology in the model show similarities to those observed in auto-immune driven fibrotic diseases such as systemic sclerosis and interstitial lung disease (ILD).
Redx Pharma’s RXC007, dosed orally and therapeutically, was able to significantly reduce skin thickness, fibrosis and collagen deposition in the skin and lungs as measured by hydroxyproline (a key fibrotic marker), histological staining and scoring (Trichome, H&E and Ashcroft score).
RXC007 is currently in development for lung fibrosis, including idiopathic pulmonary fibrosis (IPF) and auto-immune related interstitial lung disease (ILD), and the poster also discussed phase 1 safety data in healthy volunteers which highlighted an excellent safety and pharmacokinetic profile.
No adverse events were observed in the Single Ascending Dose phase, following single doses of 2-70mg (dosed once or twice in a day), and no serious adverse events were observed in the multiple dose phase (dosed at 50mg twice daily for 14 days), with only transient, reversible, mild adverse events observed.
The pharmacokinetics were as predicted from preclinical data, with linear exposure for 2-70 mg, and biologically relevant exposures achieved from 20mg. No significant effect on exposure was seen when dosed with food. The data also showed a half-life of approximately nine to 11 hours, suitable for once-daily dosing.
Reds Pharma’s plans for a phase 2 program
Redx Pharma has previously confirmed plans for a staged phase 2 clinical development program in IPF. A 12-week randomized placebo-controlled phase 2a dose-ranging study assessing early efficacy, safety and tolerability, in addition to target and disease biomarker engagement, both with and without standard of care agents, is expected to commence in Q4 2022. Topline data from this study is expected to be available in H2 2023. The phase 2a study will inform the dose selection for a subsequent larger phase 2b 12-month study.
Jane Robertson, chief medical officer at Redx Pharma, said: “We are excited by this new preclinical data which supports our current and future clinical development plans. RXC007 has now shown anti-fibrotic effects in a range of preclinical models which, combined with the encouraging Phase 1 safety and pharmacokinetic profile, underpins our plan to commence a phase 2a trial in IPF during Q4 2022.
“IPF only accounts for about a third of patients who have significant fibrotic lung pathology, and this new preclinical data supports broader clinical development of RXC007 in lung fibrosis including progressive fibrotic interstitial lung disease, which we intend to explore during our future phase 2b study.”