Date: 2017-04-05
Type of information: Milestone
Compound: HTL-1071 (AZD4635) and potential additional A2A receptor-blocking compounds
Company: AstraZeneca (UK) Heptares Therapeutics (UK), a subsidiary of Sosei Group (Japan)
Therapeutic area: Cancer - Oncology
Type agreement: licensing - development - manufacturing - production - commercialisation
Action mechanism: adenosine A2A receptor antagonist. Tumour cells have developed mechanisms to evade the immune system, including through the production of a natural molecule called adenosine. By stimulating A2A receptors, adenosine stops T-cells within the immune system from proliferating and reduces their ability to destroy cancer cells. Blocking A2A receptors can therefore promote the anti-cancer response of T-cells within in the tumour microenvironment.
Disease:
Details:
- • On August 6, 2015, AstraZeneca and Heptares Therapeutics, the wholly-owned subsidiary of Sosei, announced that they have entered into a licensing agreement under which AstraZeneca will acquire exclusive global rights to develop, manufacture and commercialise the adenosine A2A receptor antagonist, HTL-1071, a small molecule immuno-oncology candidate, and potential additional A2A receptor-blocking compounds. AstraZeneca will explore the assets across a range of cancers, including in combination with its existing portfolio of immunotherapies. Under the terms of the agreement, Heptares will grant AstraZeneca an exclusive license to research, develop, manufacture and commercialise HTL-1071. The companies will also collaborate to discover further A2A receptor-blocking compounds for development in cancer immunotherapy.The transaction is subject to customary clearances under the Hart-Scott-Rodino Antitrust Improvements Act.
Financial terms: Heptares will receive an upfront payment of $10 million and is eligible to receive additional, significant near term milestone payments based on agreed pre-clinical and/or clinical events. Subject to successful completion of development and commercialisation milestones, Heptares is also eligible to receive more than $500 million, as well as up to double-digit tiered royalties on net sales.
Latest news:
- • On April 5, 2017, Heptares Therapeutics announced that it has achieved an important milestone in its 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 that the achievement has triggered a US$12 million payment from AstraZeneca.
- 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) 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.
- • On July 6, 2016, Heptares Therapeutics announced it has been notified byAstraZeneca that the first subject has been dosed with immuno-oncology candidate HTL1071 (AZD4635) in a phase 1 clinical study, triggering a $10 million payment from AstraZeneca. The first-in-human study is being conducted by AstraZeneca in approximately 50 patients with advanced solid malignancies and with non-small cell lung cancer. The primary objective is to determine the maximum tolerated dose (MTD) of HTL1071 alone and in combination with durvalumab (MEDI4736), an investigational human monoclonal antibody directed against PDL1. Pending the determination of the MTD, a Phase 2 trial is planned to investigate further the safety, tolerability, pharmacokinetics and anti-tumour activity of the selected doses.
Is general: Yes
