▪ Redx Pharma’s virtual R&D event focussed on its two lead wholly owned assets: RXC004, a porcupine inhibitor shortly set to start its first Phase II trial in genetically selected Wnt-ligand driven cancers, and RXC007, a ROCK2 inhibitor that, following promising initial Phase I data, is expected to enter Phase II studies in idiopathic pulmonary fibrosis in 2022. Building on our September 2021 Update which covered these assets, we highlight new or relevant information emerging from the management and key opinion leader presentations from Prof Scott Kopetz (MD Anderson), Prof Gisli Jenkins (Imperial College London), and Prof Toby Maher (Keck Medicine, USC LA). ▪ Effective targeting of the Wnt pathway has been a clinical goal in many solid tumours, notably mCRC (metastatic colorectal cancer) where it plays a critical role in aggressive disease. mCRC outcomes remain very poor, with median survival of 30 months and five-year survival of 12%. MSS mCRC has an even worse prognosis, and anti-PD-1 checkpoint inhibitors have not shown any monotherapy efficacy. In Q421 RXC004 will begin a Phase II monotherapy programme in genetically selected MSS mCRC and pancreatic cancers, and in biliary tract cancer. A CPI-combination (nivolumab) arm in MSS mCRC will start in H122. Success here would not simply address a genetically specified tumour population but could help unlock the potential of CPIs in mCRC. ▪ RXC007 is a highly specific ROCK2 inhibitor that targets a nodal point in the fibrosis pathways. Historically addressing ROCK without encountering safety issues has proven difficult. Kadmon’s Rezurock (belumosudil) is the first and only approved ROCK2 inhibitor, for cGvHD, which established a regulatory pathway. Early RXC007 Phase I data following a single dose of 2mg through to 40mg has confirmed preclinical pharmacokinetics, with no adverse effects. Although already at the predicted biologically relevant doses, further escalations are continuing. Full Phase I data are expected in H122. ▪ The promise of RXC007 will be explored further in a staged Phase II study in idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a poor prognosis despite two approved products. A Phase IIa safety and tolerability study in IPF with and without standard of care (SoC) will start in 2022 and will inform the Phase IIb dose. The 12-month Phase IIb trial will then evaluate RXC007 plus SoC with forced vital capacity (FVC) lung function as a primary endpoint. If successful here, other fibrotic indications could be explored.