AstraZeneca has moved to strengthen its respiratory disease pipeline, wagering $400 million in biobucks for the global rights to a preclinical C4X Discovery NRF2 activator program with applications in chronic obstructive pulmonary disease (COPD).
Interest in targeting NRF2 to treat COPD and other diseases dates back more than a decade. Initially, the work focused on covalent modification of cysteine residues on KEAP1, which regulates NRF2, but poor selectivity and off-target toxicity led some groups to change tacks. Specifically, the groups sought to block the protein-protein interaction between KEAP1 and NRF2.
GSK published a paper on its work in the area in 2016 and followed up with a report of the development of a second, distinct series of KEAP1 inhibitors last year. In parallel, C4X worked to prepare its candidate for partnering.
Now, C4X’s efforts have resulted in a deal with AstraZeneca. The Big Pharma is paying $2 million upfront for worldwide rights to the program. With AstraZeneca on the hook for up to $16 million in preclinical paydays, C4X CEO Clive Dix told investors to expect “significant milestones” over the next two years. The bulk of the potential milestones, which top out around $400 million, are due further down the line.
AstraZeneca has identified COPD as its lead focus for the program. C4X thinks the program has broader potential that includes other respiratory diseases, immune-mediated indications including dermatology and inflammatory bowel disease, and rare conditions such as sickle cell disease. Bhavna Hunjan, chief business officer at C4X, said the broad potential was “a strong feature” of talks with AstraZeneca.
The deal provides further validation of C4X’s DNA-based target identification and candidate molecule generation capabilities. Last year, Sanofi licensed an oral IL-17A inhibitor program from C4X for 7 million euros ($7.3 million) upfront. C4X offloaded both programs during preclinical, but Dix said the company may hold on to other candidates for longer in the future.
Shares in C4X jumped 32% to 27 pence ($0.33) in early trading in London.