Targeting angiogenesis, the formation of new blood vessels around a tumour, has been one of the most successful strategies in cancer drug development over the last twenty years, with Avastin® (bevacizumab), the first drug in the class, delivering US$ 7 billion in annual sales. However, almost all patients eventually develop resistance. Novel drugs targeting lymphangiogenesis, the formation of new lymphatic vessels around the tumour, have the potential to treat many types of cancer, and to prevent the spread of cancer (metastasis) to other parts of the body.
EVT801 was invented by Sanofi SA (Paris, France), and licensed to Evotec SE (Hamburg, Germany) in 2015. Kazia entered into a worldwide exclusive license agreement with Evotec in March 2021.
A Novel Target, and a First-in-Class Drug Candidate
EVT801 is an inhibitor of VEGFR3, a cellular receptor for VEGF. Ordinarily, circulating VEGF in the bloodstream binds to receptors such as VEGFR3 and causes the development of new blood vessels and lymphatic vessels. By inhibiting VEGFR3, EVT801 aims to starve the tumour of vital nutrients, and thereby retard its growth.
The lymphatic system is also thought to be one of the principal routes by which some tumours metastasise, or spread to distant parts of the body. By inhibiting the development of new lymphatic vessels, EVT801 may be able to reduce the incidence of metastases, making tumours more amenable to local treatments such as surgery.
In addition, it has become clear in recent years that VEGF and its receptors such as VEGFR3 are involved in controlling the immune micro-environment around the tumour. The current generation of immuno-oncology drugs only works in certain types of cancer, and the key reason for failure is thought to be a lack of immune cells in some tumours. EVT801 has shown the ability to increase the infiltration of these immune cells in the laboratory, and this might provide synergistic activity with immuno-oncology drugs in the future.
Phase I Ready
Kazia expects to begin a first-in-human phase I clinical trial during CY2021. As is common with new cancer drugs, this first study will focus primarily on understanding safety, dosing, and the duration of the drug’s activity in the human body.
After completion of a successful phase I study, Kazia anticipates futher studies to provide definitive clinical proof of concept. Provisionally, hepatocellular carcinoma (liver cancer), renal cell carcinoma (kidney cancer), and sarcoma have been identified as high-potential target indications.