RXC007 – ROCK2 inhibitor for the treatment of fibrosis
ROCK2 (Rho Associated Coiled-Coil Containing Protein Kinase 2) is an intracellular kinase with multiple cellular functions. ROCK2 signalling plays a key role in both the inflammatory component and the tissue re-modelling that drives disease progression in many fibrotic conditions. ROCK2 expression and activity have been shown to be upregulated in acute inflammatory injury and in chronic diseases such as diabetes, metabolic syndrome and idiopathic pulmonary fibrosis (IPF). Furthermore, ROCK2 activity is also upregulated in liver, lung and kidney models of fibrosis. ROCK2 has been shown to modulate activation of the hepatic stellate cells – (central drivers of fibrosis in the liver) and mesangial cells (important drivers of fibrosis in the kidney). ROCK2 has also been shown to play important roles in the pro-fibrotic response of lung epithelial cells in IPF. Selective inhibition of ROCK2 also prevents the hypotensive side effects typically associated with systemic pan-ROCK inhibitors (dual ROCK1 and ROCK2 inhibition).
In H1 2020, we nominated RXC007, a novel, orally active ROCK2 inhibitor as our next drug development candidate in fibrosis, to be developed as a best-in-class treatment with potential to address multiple diseases with underlying fibrosis, including IPF, NASH and diabetic nephropathy. We aim to initiate a phase 1 study with RXC007 in H1 2021, whilst evaluating clinical development pathways in IPF and potentially in other disease areas.
Redx series of highly selective ROCK2 inhibitors have demonstrated a good ADME profile and robust anti-fibrotic effects in a range of industry-standard in vivo preclinical models (see “Presentations & Publications” further below)