Oral NRF-2 activator programme
C4XD has designed and discovered novel potent activators of the NRF-2 pathway, which is important in mediating lung diseases such as chronic obstructive pulmonary disease (“COPD”), pulmonary arterial hypertension (“PAH”), and other inflammatory diseases. In addition, recent scientific attention for this target has also extended to Sickle Cell Disease (“SCD”) where pre-clinical data suggests that the anti-oxidant and anti-inflammatory activity provided by NRF-2 activators may ameliorate haemolysis-related complications such as severe pain episodes, organ damage, heart attacks and stroke.
COPD represents an area of substantial unmet medical need and a $41 billion market and, therefore, activators of NRF-2 are the subject of considerable interest by the pharmaceutical industry. GSK has filed several further patents on its molecules against this target in the last 12 months and is likely to be close to clinical development. C4XD has made critical progress in the programme recently, with multiple C4XD compounds now shown to significantly increase NRF-2 activation in the lungs and other target tissues following low dose oral administration in pre-clinical studies. These novel compounds are currently being optimised for solubility and pharmacokinetic properties ahead of pre-clinical candidate short-list selection.