AstraZeneca continues to push its immuno-oncology programme hard, signing two new deals this week with Heptares and Mirati Therapeutics.
AZ’s MedImmune subsidiary has just licensed exclusive rights to Heptares’ adenosine A2A receptor antagonist HTL-1071 – a small-molecule immuno-oncology compound – for $10m upfront and around $500m in milestone payments.
Meanwhile, the company has also agreed to tests its lead cancer immunotherapy durvalumab (MEDI4736) in combination with Mirati’s histone deacetylase (HDAC) inhibitor mocetinostat in a phase I/II trial.
AZ has made immuno-oncology one of the key pillars of its R&D strategy as it tries to catch up with the leaders in the field, which include Bristol-Myer Squibb with Opdivo (nivolumab) and Yervoy (ipilimumab) and Merck & Co with Keytruda (pembrolizumab).
The new therapeutic category – which uses drugs to encourage the immune system to react to tumours – is predicted to be worth upwards of $30bn within the next 10 years.
The adenosine A2A receptor is thought to be responsible for inactivating and inhibiting T lymphocytes from invading tumours, so blocking it could improve cancer immunotherapy by allowing T cells and natural killer cells to fight tumour cells.
In addition to gaining rights to HTL-1071, which is currently in early-stage development, AZ and Heptares – which was acquired by Japan’s Sosei in February in a deal valued at around $400m – have agreed to work together on identify additional adenosine ARA antagonists.
AZ has been working with UK-based Heptares since 2011 in a $190m programme looking at the development of drugs for central nervous system disorders/pain, cardiovascular and metabolic diseases and inflammation.
The agreement with Mitari is the latest of a series signed by AZ and MedImmune to explore the use of durvalumab in combination with other drugs, which is a feature of the immuno-oncology sector.
Durvalumab is a checkpoint inhibitor designed to counter tumours’ immune-evading tactics, while mocetinostat has the potential to enhance the positive effect of the drug on tumour immunity.
The latter is in the same class as Merck & Co’s Zolinza (vorinostat), Novartis’ Farydak (panobinostat) and Spectrum Pharmaceuticals’ Beleodaq (belinostat), which are approved for various haematological cancers.
AZ and Mitari will initially test their combination in non-small cell lung cancer (NSCLC) in a trial due to start next year, with other indications following if initial studies are successful.