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AZD4635 (HTL-1071), a novel adenosine A2A receptor antagonist, reverses adenosine-mediated T-cell suppression and enhances anti-tumour immunity
New preclinical results presented at AACR Annual Meeting
Heptares Therapeutics (“Heptares”), a wholly owned subsidiary of Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565), announces that it has achieved an important milestone in its immuno-oncology collaboration with AstraZeneca, which is focused on the development of AZD4635 (HTL-1071) as a potential new treatment for a range of cancers. As a result, Heptares has been notified today that the achievement has triggered a US$12 million payment from AstraZeneca.
AZD4635 is a potent and selective, orally available, small molecule adenosine A2A receptor antagonist discovered by Heptares and licensed to AstraZeneca in 2015.
The milestone was triggered by the successful completion of a preclinical programme that demonstrated a clear effect of AZD4635 in reversing adenosine-mediated T-cell suppression and enhancing anti-tumour immunity. Blockade of A2A signalling with AZD4635 was found to reduce tumour growth when used alone and in combination with anti-PD-L1 checkpoint inhibitors. Results from this programme will be presented by scientists from Heptares and AstraZeneca in a poster (abstract 5580) today at the American Association of Cancer Research Annual Meeting (1-5 April, 2017; Washington, DC, USA).
AZD4635 is currently in a Phase 1 clinical trial as a single agent and in combination with AstraZeneca’s durvalumab (anti-PD-1L antibody) in patients with solid malignancies.
Tumour cells have evolved mechanisms to evade the immune system, including through the production of a natural anti-inflammatory molecule called adenosine. By stimulating A2A receptors, adenosine prevents T-cells within the immune system from being activated and reduces their ability to destroy cancer cells. Blocking A2A receptors can therefore promote the anti-cancer response of T-cells within the tumour microenvironment.
“The preclinical study results are very exciting and confirm that inhibition of A2A signalling offers an attractive mechanism to treat cancers by preventing tumours from evading the immune system and making them susceptible to checkpoint inhibitors,” said Fiona Marshall, CSO of Heptares and Sosei. “We now look forward to the results from the first clinical study with AZD4635 around the end of the year.”