UNITED KINGDOM — C4X Discovery Holdings (C4XD), based in Manchester, has signed an exclusive global licensing agreement worth up to US$402 million with pharmaceutical giant AstraZeneca.

C4XD’s NRF2 Activator program is linked to the treatment of inflammatory and respiratory diseases, with a primary focus on chronic obstructive pulmonary disease (COPD).

AstraZeneca, which employs approximately 4,700 people in the North West at sites in Cheshire’s Macclesfield and Alderley Park, as well as Merseyside’s Speke, will develop and commercialize an oral therapy.

C4XD will receive up to US$16 million in pre-clinical milestone payments ahead of the first clinical trial, including US$2 million upfront, according to the terms of the agreement.

Dr. Clive Dix, CEO of C4XD, said: “Drug discovery is inherently scientifically complex, and it is through our unique expertise and proprietary cutting-edge technologies that C4XD is yet again proving itself as an exemplar in this field.

NRF2 (nuclear factor erythroid 2–related factor 2) is thought to be a critical but challenging anti-inflammatory target, and I am proud of the work by our team to achieve a broad stable of intellectual property for this program, leading to our third significant deal with a truly world-renowned industry leader.

The COPD market alone is worth close to US$20bn and rising.

Inflammation is a major contributor to a wide range of pathological conditions, including respiratory diseases.

NRF2 is a key natural regulator that controls the expression of antioxidant genes and is involved in both cellular defense against external insults and the regulation of the inflammatory response.

Targeting the NRF2 pathway to reduce inflammatory damage holds the promise of a novel approach to treating a variety of inflammatory diseases, including COPD, where activation of NRF2 may aid in reducing the negative effects of oxidative stress-induced disease progression.

C4XD’s oral NRF2 Activator lead molecules have been found to significantly activate NRF2 after oral dosing, providing anti-inflammatory and antioxidant activity.

C4XD raised £5.7 million (US$6.9 billion) in August through a share placement with its institutional directors.

The offering aided corporate development and ongoing commercial activities. The company stated that the net proceeds of the offering would be used to strengthen the balance sheet as partnering discussions progress, to continue developing the company’s portfolio of early-stage, high-value small molecule programs, and to validate the next generation of commercially attractive targets, and programs.

The net proceeds of the offering were expected to provide C4XD with at least a year’s worth of working capital.

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