If Sosei’s acquisition of the UK neuroscience company Heptares in February took the Japanese group out of its comfort zone then today’s deal between Sosei and AstraZeneca goes one step further.
The tie-up, worth $10m up front, centres on a Heptares-originated adenosine A2A antagonist – a mechanism that is associated mainly with Parkinson’s disease, but which Astra now wants to test in oncology. The approach has scientific backing, and it will be interesting to see whether Astra’s bet breathes new life into similarly acting CNS projects.
Most prominent among these would be Biotie’s tozadenant, an A2A antagonist that recently began a phase III trial in 450 Parkinson’s disease patients under a US special protocol assessment. Last year the Finnish group lost UCB as a licensing partner.
One of the few industry players to have looked at oncology applications of this mechanism is Palobiopharma, a private Spanish biotech, which has put PBF-509 through a phase I NSCLC trial. Astra’s deal, while financially modest, nevertheless represents a significant big pharma endorsement for what is still at present a preclinical concept.
Impaired T-cell function
The relevance of targeting the A2A receptor in oncology stems from the finding that adenosine plays a role in the tumour microenvironment, inhibiting T-cell proliferation and impairing T-cell function.
And, though the pharmacology is complex, the theory is that blocking the A2A receptor could reverse this effect, promoting T-cell-mediated antitumour activity. Astra’s deal focuses on HTL-1071 and follow-up compounds; Heptares has previously looked at A2A antagonists in attention deficit hyperactivity disorder.
For Astra this represents a reasonably low-cost entry into yet another field of immuno-oncology. Just yesterday the group agreed with Mirati Therapeutics to combine Mirati’s HDAC inhibitor mocetinostat with its own anti-PD-L1 MAb durvalumab in a phase I/II NSCLC study.
Several HDAC inhibitors are already on the market, including Novartis’s Farydak, Merck & Co’s Zolinza and Celgene’s Istodax. But sales have been underwhelming, while development of another agent, the German group 4SC’s resminostat, for instance, has proceeded at a glacial pace.
Meanwhile, other A2A antagonists in clinical development – all in Parkinson’s – include Vernalis’s V81444, which was ditched by Biogen, and Sigma-Tau’s ST4206. Only one is marketed – Kyowa Hakko Kirin’s Nouriast – and that is available only in Japan, having suffered a knockback from the US FDA.
The most epic failure of an A2A antagonist was that of preladenant, ditched by Merck & Co after flunking three phase III trials two years ago. Since then hopes of a resurrection have amounted to little (Biotie mulls second chance for Parkinson’s drug, September 22, 2014).
Although Astra’s bet will not save the drug class in neuroscience it presents oncology as an alternative avenue.