C4X Discovery Holdings inks $402m deal with AstraZeneca

Under the agrrement, C4X Discovery Holdings plc (C4XD) will receive pre-clinical milestone payments worth up to $16m ahead of the first clinical trial, including $2m upfront. In addition, C4XD is eligible to receive a further potential $385.8 million in clinical development and commercial milestones and tiered mid-single digit royalties upon commercialisation AstraZeneca intends to develop and commercialise an oral therapy for the treatment of inflammatory and respiratory diseases with a lead focus on chronic obstructive pulmonary disease (COPD) based on the licensed NRF2 Activator programme.

Inflammation is a key driver in many pathological conditions including respiratory diseases. NRF2 is an important natural regulator, controlling the expression of antioxidant genes, and it plays a key role in cellular defense against external insults, as well as the regulation of the inflammatory response. Targeting the NRF2 pathway to reduce inflammatory damage offers the potential for a new approach to treat a variety of inflammatory diseases such as COPD, where activation of NRF2 may help in reducing the negative effects of the oxidative stress-induced progression of the disease. Lead molecules from C4XD’s oral NRF2 Activator programme have been found to significantly activate NRF2 following oral dosing, providing anti-inflammatory and antioxidant activity.

COPD drugs promise a significant return on investement as the disorder is the third leading cause of death worldwide, causing 3.23 million deaths in 2019. It is a common, preventable and treatable chronic lung disease. Abnormalities in the small airways of the lungs lead to a narrowing of the airways, limiting airflow in and out of the lungs and destruction of parts of the lung may be observed.5 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.6

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