Dizal Announces the Latest Publication of DZD2269 in Journal of Experimental & Clinical Cancer Research

Dizal Pharmaceutical Co., Ltd ("Dizal", SHEX: 688192) today announced the latest publication of translational science and early clinical results of DZD2269, a potent and selective A2aR antagonist capable of fully blocking A2aR mediated immunosuppression at high adenosine concentrations commonly found in tumor microenvironment in the Journal of Experimental & Clinical Cancer Research (IF:12.658). Extracellular adenosine is a potent immunosuppressive metabolite. Binding of adenosine to its receptor leads to immunosuppression. While adenosine concentration is normally low in healthy individuals, its level could be thousand-fold higher in tumor microenvironment. Several A2aR antagonists are under clinical development, with limited clinical benefit reported so far. The paper noted that these agents, while potent when measured at low adenosine concentrations, all lost their activities when measured at higher adenosine concentrations commonly found at the tumor microenvironment. The paper suggested that this could explain their clinical underperformance. DZD2269 is a designed as a potent and selective A2aR antagonist, capable of reversing the immunosuppression induced by high concentrations of adenosine. This was validated by a series of cellular and animal models published in the paper. DZD2269 alone showed anti-tumor activity in immunocompetent mouse models, and when in combination with radiotherapy, chemotherapy, or immune checkpoint inhibitors, its anti-tumor effect was significantly enhanced. Notably, when radiation and DZD2269 were given simultaneously, a significant synergistic effect was observed, consistent with the scientific hypothesis. These combination strategies can provide new treatment modalities for the cancer patients, especially for those with early disease and more robust immune functions. Data from an ongoing phase 1 study showed DZD2269 had good PK/PD correlation and excellent safety profile. Downregulation of pCREB was detected in human T cells in a dose-dependent manner, indicating that DZD2269 can fully block A2aR mediated immunosuppression even at the highest adenosine concentrations tested. These data support further clinical development of DZD2269 in multiple solid tumors. "No approved A2aR antagonist yet. We have identified a potential mechanism why these 1st generation A2aR antagonists underperformed in clinical studies, " said Dr. Xiaolin Zhang, Correspondence Author of this paper and CEO of Dizal, “DZD2269 is designed as an A2aR antagonist able to overcome high level of adenosine mediated immunosuppression. Based on these promising findings, we are excited to see that the preliminary clinical data is consistent with the preclinical prediction." About A2aR antagonist Extracellular adenosine is a potent immunosuppressive metabolite. Adenosine exerts its biological effect through four adenosine receptors, A1R, A2aR, A2bR and A3R. Available evidence suggests that A2aR is the key mediator for its immune suppressive effect. Abolishing adenosine-mediated immune-suppression as a potential immune-oncology therapy has been under investigation. Directly blocking adenosine’s binding to its suppressive receptor A2aR is one of the preferred approaches and several A2aR antagonists are at early-stage clinical investigation. About Dizal Dizal is a clinical-stage, biopharmaceutical company, dedicated to the discovery and development of differentiated therapeutics for the treatment of cancer and immunological diseases. Deep-rooted in translational science and molecular design, it has established an internationally competitive portfolio of five clinical-stage assets with two leading assets in global pivotal studies. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", and "intend" and similar expressions, as they relate to Dizal, are intended to identify certain forward-looking statements. Dizal does not intend to update these forward-looking statements regularly.These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections, and understandings of the management of Dizal with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties, and other factors, some of which are beyond Dizal's control and are difficult to predict. 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