Case Study

We are always looking for new collaborations and partnerships that support our mission to push the boundaries of drug discovery and deliver faster, better treatments for patients all over the world. If you would like to partner with us, we would love to hear from you.  

Adenosine A2a Antagonist

Our collaboration with Evotec focuses on a number of high-interest targets for adenosine focused immuno-oncology where it is now recognised that high levels of adenosine can suppress the native immune response.

Our most advanced project is the development of a novel A2a antagonist. Whilst the majority of companies have focused on the repurposing of existing experimental Parkinson compounds we have decided to take a different approach in order to discover a best-in-class molecule that is clearly differentiated from competitors.

Our differentiated approach is based on the fact that we must be highly selective for A2a over all other adenosine receptors and also avoid CNS penetration, which is a characteristic of all the A2aParkinson compounds undesirable in an immuno-oncology setting where high doses may be required.

To initiate the project, we took a multifaceted approach recognising that patent space was already busy whilst none of the existing compounds had the CNS avoidance we wanted. We built high-value adenosine family models from published literature and patents and seeded a hit finding with an in-house SPR screen of the native Adenosine receptor. The combination of the two proved to be extremely powerful. From early fragment hits, we rapidly moved through to a lead series and finally a Candidate compound within 200 compounds. The 178th compound synthesised was considered to have the best overall properties performing well in in vivo efficacy testing as well as successful avoidance of CNS effects. This compound has since been taken into IND enabling studies.