Date: 2015-01-22
Type of information: Milestone
Compound: new medicines targeting G-protein coupled receptors (GPCRs)
Company: AstraZeneca (UK) Heptares Therapeutics (UK)
Therapeutic area: CNS diseases - Cardiovascular diseases - Metabolic diseases - Inflammatory diseases
Type agreement: R&D
Action mechanism:
Disease: CNS diseases - Cardiovascular diseases - Metabolic diseases - Inflammatory diseases
Details: * On May 31, 2011, AstraZeneca and Heptares Therapeutics have entered a four-year collaboration focused on the potential discovery and development of new medicines targeting G-protein coupled receptors (GPCRs). This collaboration brings together Heptares’ GPCR discovery expertise and proprietary technologies, including its StaR® technology, which engineers stabilized receptors allowing GPCRs to be investigated, with AstraZeneca’s biopharmaceutical discovery, development and commercial capabilities. Research conducted under the collaboration will focus on a number of specific GPCR targets linked to central nervous system/pain, cardiovascular/metabolic and inflammatory disorders from projects in AstraZeneca’s small and large molecule portfolio, including projects from AstraZeneca’s biologics unit, MedImmune. This research will act as the starting point for drug discovery by producing the first-ever stabilized forms of GPCRs in their natural pharmacological conformation. As part of a joint discovery effort, Heptares and AstraZeneca will engage their respective discovery teams, compound libraries, and other discovery technologies for the purposes of initial screening and lead identification. Results will be combined into a common pool and the best leads will be further optimised collaboratively. AstraZeneca will then select pre-clinical, small and large molecule candidates and will be solely responsible for preclinical and clinical development.
Financial terms: Under the terms of the agreement, AstraZeneca has worldwide commercial rights to product candidates emerging from the collaboration. Heptares will receive an upfront $6.25 million cash payment fee plus committed research funding and also qualifies for significant future payments depending on delivery of agreed milestones. Heptares will also receive royalties on sales of all products discovered through the joint research.
Latest news: * On January 22, 2015, Heptares Therapeutics announced significant progress in its drug discovery collaboration with AstraZeneca. Using Heptares proprietary StaR® technology, the first-ever stable version of Protease-Activated Receptor-2 (PAR2) in a therapeutically relevant form has been generated, from which its X-ray structure has been solved. PAR2 is a G protein-coupled receptor (GPCR) that is a well-validated target for multiple indications in pain and inflammatory diseases. Working with scientists at AstraZeneca, the PAR2 StaR protein was used to screen compound libraries resulting in the identification of a hit series of small molecules that bind and block its activity. The X-ray structure information, which yields new details about the unusual binding pocket of PAR2, is now being used at AstraZeneca to further optimize the hit molecules; to increase their binding affinity, potency as antagonists as well as improving their drug-like properties (e.g. oral bioavailability and stability).PAR2 is an unusual GPCR that is activated by cleavage with a protease enzyme. The receptor is expressed on primary afferent neurons involved in pain sensation. PAR2 appears to play a key role in neurogenic inflammation and pain in particular associated with cancer, osteoarthritis and gastrointestinal pain. Because of the unusual mechanism of activation, which leaves part of the receptor to act as its own ligand, it has proved extremely difficult to identify small molecule antagonists which could be used as a treatment for such pain conditions.* On January 23, 2014, Heptares Therapeutics has announced that it has successfully completed the research phase of its antibody drug discovery collaboration with MedImmune, the global biologics research and development arm of AstraZeneca. In achieving this milestone, Heptares has delivered StaR® proteins (thermostabilised G protein-coupled receptors, GPCRs) for its targets nominated by MedImmune for antibody discovery as part of the research collaboration initiated in May 2011. For each project, nomination of the target and delivery of the StaR protein resulted in milestone payments to Heptares from MedImmune.
