AstraZeneca notified its partner Heptares Therapeutics that the first patient has been dosed in a Phase 1 clinical trial with immuno-oncology drug HTL1071 (AZD4635), initiating a $10 million payment from AstraZeneca.
HTL1071 is an orally available, small molecule adenosine A2A receptor antagonist, and the lead immuno-oncology drug among A2A antagonists discovered by Heptares using its proprietary structure-based drug design platform.
Tumor cells have developed several ways to evade the immune system, including the production of adenosine, a natural compound that plays an important role in biochemical processes such as energy transfer.
By stimulating A2A receptors, adenosine stops immune T-cells from multiplying and lowers their ability to destroy cancer cells. Blocking A2A receptors can promote anti-cancer responses of T-cells within the tumor environment.
The first-in-human clinical trial of HTL1071 is evaluating the effects of the compound in 50 patients with advanced solid malignancies and with non-small cell lung cancer (NSCLC). The primary endpoint of the Phase 1 trial is to determine the maximum tolerated dose (MTD) of HTL1071 used as a single agent or combined with durvalumab (MEDI4736), a human monoclonal antibody directed against PDL1.
Upon determination of the MTD, AstraZeneca is going to move HTL1071 into a Phase 2 clinical trial to further evaluate its pharmacokinetics, safety, and tolerability as well as anti-tumor activity of the selected doses.
“The production of adenosine is a recently identified mechanism employed by tumor cells to suppress T-cell activity and evade destruction,” Tim Tasker, chief medical officer at Heptares, said in a recent press release. “The initiation of this first clinical study in the A2A antagonist immuno-oncology program with AstraZeneca is an important milestone for Heptares and we are excited to see how the results from preclinical studies translate into potential new medicines for cancer patients.
“This is the second program in our partnered pipeline to progress into the clinic, the first being the M1 agonist program, licensed to Allergan, in which two novel compounds are undergoing clinical studies as potential new medicines for cognitive impairment in Alzheimer’s disease and other neurological indications,” he said.
Susan Galbraith, vice president and head of oncology in AstraZeneca’s Innovative Medicines and Early Development Unit, said immuno-oncology is one of four key oncology platforms for AstraZeneca.
“In building our immuno-oncology portfolio, we believe that blocking adenosine A2A receptor could enhance the efficacy of immune checkpoint inhibition via PDL1, CTLA4 and enhance the activity of CD73 inhibition,” she said. “This innovative approach could help drive an immune attack on cancers, creating novel treatments with the potential to transform the lives of patients.”
