ET-D5

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 in the world (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 recently the major improvements in the cancer management have come from the development of new drugs.
Our mission at Ecrins Therapeutics is to discover and develop novel anti-cancer molecules into efficacious drugs to treat cancer. Ecrins’ 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, Protein Phophatase 1 (PP1), involved in cancer progression. 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 on our phenotypic screening platform. ET-D5 demonstrated great anti-tumoral 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.

ET-D5 veterinary oncology project development

At Ecrins Therapeutics we love companion animals. We also share the feeling that we humans owe a lot to dogs: to limit dangers to humans, many drug candidates are first tested on dogs before being given to humans. We’d like to give back to them, so that they too can benefit from the progress made in oncology.
Similarly to our human oncology program, we intend to use ET-D5 in order to treat cancer in companion animals: dogs and cats.

Ecrins Therapeutics aims to develop ET-D5 for the treatment of cancer in dogs, and to put this new therapy on the market. For this, Ecrins Therapeutics launched two projects:

In 2015, Ecrins Therapeutics won the EUREKA transnational grant for the CADAC (Canine Antivascular Drug Against Cancer) project. TThe CADAC’s objective was to test ET-D5 in a clinical trial in dogs with spontaneous cancers. For this, Ecrins Therapeutics worked with AOIC (Animal Oncology and Imaging Center), an animal oncology center based in Switzerland. The project ended in August 2019.

For the project Dog-To-Man, Ecrins Therapeutics teamed together with two academics partners (CLB – Lyon, and IGDR – Rennes), and one private veterinary clinic (ORC – Lille), in order to evaluate the efficacy of ET-D5 in canine sarcomas. The project represents a classic case of translational research, meaning that we have two goals: to identify a new treatment for canine sarcomas, and to use the obtained knowledge to guide the treatment of human patients suffering from sarcomas.