C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, has signed an exclusive worldwide licensing agreement with AstraZeneca worth up to $402 million1, for its NRF2 Activator programme. AstraZeneca will develop and commercialise an oral therapy for the treatment of inflammatory and respiratory diseases with a lead focus on chronic obstructive pulmonary disease (COPD).

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

Sir Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: "At AstraZeneca, we are committed to transforming care in respiratory and immune-mediated disease and move beyond symptom control. 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."

Dr Clive Dix, CEO of C4XD, added: "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 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 programme, leading to our third significant deal with a truly world-renowned industry leader. The COPD market alone is worth close to $20 billion and rising.2 But, more importantly, I know that in AstraZeneca'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." 

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.3,4. 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.


C4X Discovery Holdings  
Mo Noonan, Communications +44 (0)787 6444977
Panmure Gordon (UK) Limited (NOMAD and Broker)  
Freddy Crossley, Emma Earl (Corporate Finance) +44 (0)20 7886 2500
Rupert Dearden (Corporate Broking)  
C4X Discovery Media - Consilium Strategic Communications  
Mary-Jane Elliott, Chris Gardner, Matthew Neal +44 (0)203 709 5700

Notes to Editors:

About COPDCOPD 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 which affects men and women worldwide. 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

About C4X DiscoveryC4X Discovery ("C4XD") is a pioneering Drug Discovery company combining scientific expertise with cutting-edge Drug Discovery technologies to efficiently deliver world leading medicines, which are developed by our partners for the benefit of patients. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced DNA-based target identification and candidate molecule design capabilities, generating small molecule drug candidates across multiple disease areas including inflammation, oncology, neurodegeneration and addictive disorders. Our commercially attractive portfolio ranges from early-stage novel target opportunities to late-stage Drug Discovery programmes ready for out-licensing to partners and we have three commercially partnered programmes with one candidate in clinical development.

We collaborate with leading pharmaceutical and life sciences companies to enrich our expertise and take our assets through pre-clinical and clinical development. Through early-stage revenue-generating licensing deals, we realise returns from our high value pre-clinical assets which are reinvested to maximise the value of our Drug Discovery portfolio. For further information see www.c4xdiscovery.com


AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

1. Total deal value has been rounded to the nearest significant figure in US$2. https://www.transparencymarketresearch.com/chronic-obstructive-pulmonary-disease-copd-treatment-market.html3. https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-1292-74. https://link.springer.com/article/10.1007/s10787-022-00967-35. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)6. https://www.mdpi.com/2076-3921/11/5/965/pdf?version=1652446153

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