Aiming at adenosine

AstraZeneca, Heptares Therapeutics ink a licensing agreement to develop HTL-1071, an adenosince A2a receptor

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LONDON & BOSTON—AstraZeneca and Heptares Therapeutics, the wholly owned subsidiary of Sosei Group Corporation, have signed a licensing agreement by which AstraZeneca centered on Heptares' HTL-1071, an adenosine A2A receptor being developed as a small-molecule immuno-oncology candidate, as well as potential other A2A receptor-blocking compounds. AstraZeneca will evaluate the assets' effects in a variety of cancer types, including in combination with its own immunotherapies.
Per the terms of the agreement, AstraZeneca will gain exclusive global rights to develop, manufacture and commercialize HTL-1071, for which it will pay Heptares $10 million up front. Heptares also stands to receive additional near-term milestone payments if certain agreed-upon preclinical and/or clinical events are reached. If the development and commercialization milestones are reached, Heptares could receive more than $500 million in related payments, as well as up to double-digit tiered royalties on net sales of compounds resulting from this agreement. AstraZeneca and Hepatres will also collaborate on the discovery of additional A2A receptor-blocking compounds to be developed as cancer immunotherapies.
“We are pleased to expand our successful collaboration with Heptares into the exciting area of immuno-oncology,” Susan Galbraith, vice president, head of Oncology in AstraZeneca’s Innovative Medicines and Early Development Unit, remarked in a press release. “By combining the pioneering A2A receptor programme with the strength of AstraZeneca’s oncology portfolio, we hope to develop novel treatments with the potential to transform the lives of patients.”
One of the mechanisms by which tumors can evade notice by the immune system is through the production of adenosine, a natural molecule. By stimulating A2A receptors, adenosine blocks proliferation of immune T cells and reduces their ability to destroy cancer cells. Blocking these receptors can help reinstate the T cells' anti-cancer response in the tumor microenvironment.
“The A2A receptor programme at Heptares has been an outstanding example of our Structure Based Drug Design approach in action, resulting in a novel clinical candidate, HTL-1071, with a highly attractive profile. Heptares is targeting G-protein-coupled receptors that play a key role in cancer biology through the identification of both antibody and small molecule therapeutics. We are delighted to be entering this expanding field by partnering with AstraZeneca, an innovative leader in the field of cancer immunotherapy. This agreement further builds on our successful existing research collaboration,” commented Malcolm Weir, CEO of Heptares, in a statement.
That existing collaboration is a four-year agreement for the discovery and development of new medicines targeting G-protein coupled receptors (GPCRs), which AstraZeneca and Heptares announced in May 2011. The deal is focusing on several GPCR targets linked to central nervous system/pain, cardiovascular/metabolic and inflammatory disorders from projects in AstraZeneca's portfolio, with both companies applying their compound libraries and discovery technologies for initial screening and lead identification. After that, results are combined into a common pool, with the best leads to be optimized collaboratively, with AstraZeneca selecting preclinical small- and large-molecule candidates and assuming sole responsibility for preclinical and clinical development. The agreement stipulates that AstraZeneca will have worldwide commercial rights to product candidates that emerge from the deal, for which Heptares received an upfront cash payment, committed research funding and significant future payments in certain milestones are reached, in addition to sales royalties.

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