Almost a year after giving up on a non-alcoholic steatohepatitis (NASH) drug licensed from Regulus, AstraZeneca has taken another tack, buying an Ionis candidate in a deal valued at up to $330m.
The deal – which includes $30m upfront and the remainder in milestone payments – is for IONIS-AZ6-2.5-LRx, an antisense drug that addresses an undisclosed target in NASH and is still in preclinical development.
NASH is a hot topic in pharma development at the moment, with bigger companies inking licensing deals for new treatments for the disease almost every week.
Characterised by a build-up of fat that can lead to fibrosis, cirrhosis and in some patients the need for a liver transplant, NASH is viewed as an emerging health crisis – and an untapped pharma market as there are as yet no approved treatments.
It’s the third time AZ has taken up an option on an Ionis drug under a 2015 alliance in the area of cardiovascular, metabolic and kidney disease, after earlier deals for cardiovascular drug AZD8233 and kidney disease candidate AZD2373.
The two companies are also collaborating on AZD4785 – a candidate that targets the KRAS oncogene and started clinical trials in solid tumours last year – and STAT3-targeting AZD9150, which is being tested as a combination with AZ’s PD-L1 inhibitor Imfinzi (durvalumab). Another partnered antisense candidate called AZD5312 failed to hit the mark in prostate cancer trials and was abandoned in 2016.
IONIS-AZ6-2.5-LRx is one of Ionis’ new-generation antisense oligonucleotides, with chemical modifications that improve their affinity and stability versus older drugs and according to Brett Monia, the biotech’s chief operating officer, it “supports [the] administration of infrequent, very low doses, and even enables the potential for oral dosing”.
“AZ has played a strategic role in advancing this programme forward by providing both preclinical and development expertise in NASH that has contributed to the rapid advance of this drug into development,” he added. “We look forward to AZ moving this programme swiftly into clinical testing and ultimately to the market.”
Last June, AZ abandoned development of NASH drug AZD4076 – one of three drugs it licensed from Regulus Therapeutics – even though it was only a few months into a phase I/IIa trial programme for the drug in NASH associated with type 2 diabetes. AZD4076 was a microRNA-targeting oligonucleotide licensed by AZ in 2015 for $28m upfront and a little under $500m in potential milestones.