AstraZeneca (AZ) and C4X Discovery (C4XD) have signed an exclusive worldwide licensing agreement worth up to $403m to develop an oral therapy for the treatment of inflammatory and respiratory diseases using C4XD’s NRF2 Activator programme, with a focus on chronic obstructive pulmonary disease (COPD).
C4XD said it will receive pre-clinical milestone payments worth up to $16m before the first clinical trial, including $2m upfront. The drug discovery company is also eligible to receive a further potential $385.8m in clinical development and commercial milestones from AZ, as well as tiered mid-single digit royalties upon commercialisation.
COPD, a chronic inflammatory lung disease that causes obstructed airflow from the lungs, is the third leading cause of death worldwide, causing 3.23 million deaths in 2019.
Symptoms include breathing difficulty, cough, mucus production and wheezing. Cigarette smoking is a major risk factor for COPD, causing a high level of oxidative stress in the lungs and driving chronic inflammation as well as increased severity of infection-induced flare-ups.
Patients with COPD are at increased risk of developing heart disease, lung cancer and a variety of other conditions. However, despite COPD being a progressive disease, it is treatable. With proper management, most patients with COPD can achieve good symptom control and quality of life, as well as reduced risk of other associated conditions.
NRF2 is an important natural regulator controlling the expression of antioxidant genes, C4XD explained in a statement, and plays a key role in cellular defence against external insults, as well as the regulation of the inflammatory response.
Targeting the NRF2 pathway to reduce inflammatory damage therefore offers the potential for a new approach to treat a variety of inflammatory diseases such as COPD, with lead molecules from C4XD’s oral NRF2 Activator programme found to significantly activate NRF2 following oral dosing.
“Our alliance with C4XD adds an important new asset to our portfolio to push the boundaries of science by targeting underlying disease drivers to potentially modify the course of these diseases,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AZ.
Also commenting on the collaboration, Dr Clive Dix, chief executive officer of C4XD, said: “I know that in AZ’s hands, with their scientific, technical and commercial expertise, our NRF2 Activator programme has the potential to deliver life-changing treatments for the millions of patients suffering with COPD across the world.”