On December 1, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, is pleased to report the publication of positive preclinical data for EVT801, a clinical-stage drug candidate currently in a clinical trial for multiple forms of cancer (Press release, Kazia Therapeutics, DEC 1, 2022, View Source [SID1234624670]).
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The publication, by Michael Paillasse and colleagues, summarizes a large body of preclinical research conducted principally by scientists at Evotec SE and at the University Cancer Institute of Toulouse – Oncopole over a period of several years. It is now published in Cancer Research Communications, a recently-launched journal published by the American Association of Cancer Research (AACR) (Free AACR Whitepaper). The data formed the basis of Kazia’s in-licensing of EVT801 from Evotec in 2021 and has since supported transition of the compound into an ongoing phase I clinical trial in patients with advanced solid tumors.
Key Points
EVT801 is a selective inhibitor of vascular endothelial growth factor receptor 3 (VEGFR3). VEGFs and VEGFRs are well-validated cancer drug targets with multiple FDA-approved products directed to them, but a more selective VEGFR3 inhibitor, such as EVT801, may result in better tolerability and less development of resistance to therapy.
EVT801 was confirmed in preclinical studies to be a potent and selective inhibitor of VEGFR3, with activity in the low nanomolar range. The drug was shown to inhibit the formation of lymphatic vessels in vitro, confirming its intended primary mode of action.
In vivo (animal) experiments showed EVT801 to be more active than both pazopanib (Votrient, Novartis) and sorafenib (Nexavar, Bayer) in the tumor models under investigation.
EVT801 combined with immune checkpoint inhibitors in mouse models of several tumor types showed strongly synergistic activity, with the combination performing better than either drug alone. Immune checkpoint inhibitors are widely used in many cancers, and the class includes drugs such as pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol Myers Squibb), and ipilimumab (Yervoy, Bristol Myers Squibb).
"These data demonstrate the substantial potential of EVT801 as a cancer therapeutic," stated Dr Michael Paillasse, lead author of the publication. "EVT801 has been shown to act exactly as intended: by impacting the vasculature in and around the tumor. In addition, the evidence of synergy with immunotherapy is persuasive, and we see a considerable opportunity to combine the drug with immune checkpoint inhibitors in clinical trials."
"We are grateful that the results of this public-private translational research initiative have been appreciated by the editors and reviewers of Cancer Research Communications. We will now focus on the clinical development," said Professor Jean-Pierre Delord, co-author and CEO of the IUCT – Oncopole.
"We are delighted to see this exciting and comprehensive body of work now published in a leading peer-reviewed journal," said Dr James Garner, Chief Executive Officer of Kazia. "The data supports our decision last year to in-license EVT801, and clearly points to the future development strategy for the drug. Our collaboration with the Evotec team has already been extremely fruitful, and we look forward to continuing to work together on this very promising drug candidate."
The publication may be accessed via the journal website at View Source
Phase I Clinical Trial Progressing
EVT801 is currently the subject of an ongoing phase I clinical trial as monotherapy in patients with advanced solid tumors (NCT05114668). The study is progressing as planned, with patients currently being dosed within the anticipated therapeutic range. It is expected that initial data from this study will be available in 1H CY2023.
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