Cancer is a terrible disease which could affect each of us directly or indirectly. The statistics speak for themselves: deaths from cancer represent around one eighth (12%) of all deaths (World Cancer Report, 2014). The proportion of deaths caused by cancer varies, from 4% in Africa to 21-24 % in industrialized countries. These frightening statistics hide the enormous success of modern treatments: in fact, half of the people diagnosed with cancer in developed countries survive their disease for ten years or more.
The main approaches to combat cancer are surgery, radiotherapy and chemotherapy with the recent addition of immunotherapy. It would not be an overstatement to say that the major improvements in the recent past have come from the development of new drugs.
Our mission at Ecrins Therapeutics is to develop novel anti-cancer molecules into efficacious drugs to treat cancer. Our main program is ET-D5 – a small molecule drug candidate that we discovered and are developing for several oncology indications. ET-D5 is a new chemical entity (NCE) that can be administered intravenously or taken orally.
ET-D5 mechanism of action
ET-D5 is an anti-mitotic and anti-vascular compound with an original molecular target involved in cancer progression. Contrary to many anti-vascular compounds, ET-D5 does not target tubulin or protein kinases but the Protein Phophatase 1 (PP1). ET-D5 is the first drug candidate targeting PP1 (first-in-class molecule).
The inhibition of PP1 by ET-D5 leads to the destruction of tumor blood vessels and therefore effectively shuts down the supply of O2 and nutrients to cancer cells, provoking massive intratumoral necrosis (see figure on the right). Another mechanism by which ET-D5 targets cancer cells is by arresting them in division (mitotic arrest), followed by cell death. Most importantly, ET-D5 presents interesting pharmacological properties, a good toxicology profile, and is active when administered orally.
ET-D5 human oncology project development
ET-D5 was discovered, developed, and optimized from our phenotypic screening platform. ET-D5 demonstrated great anti-tumor efficacy in animal models through oral administration. Formulation and regulatory toxicology studies have been performed with success, opening the door to the first human clinical trial.