V4Cure: snake venom as a source of inspiration for drugs

2023-09-22 06:30:04

Inspired by the venom of the mamba snake, researcher Nicolas Gilles is developing the drugs of tomorrow that will treat two serious kidney pathologies within his start-up V4Cure.

Since 2009, CEA (Atomic Energy Commission) researcher Nicolas Gilles has been studying animal toxins to try to discover therapeutic candidates. Among all the substances identified, one stands out, “mambaquaretin”. Present in the venom of the mamba, a snake from sub-Saharan Africa whose bite is lethal for humans, this toxin has the particularity of blocking urinary concentration in the body without causing a loss of salt. This molecule, called V4C-232 and synthesized in the laboratory, would make it possible to treat two diseases that affect 10 million people in the West: hyponatremia and polycystic kidney disease.

In hypervolemic hyponatremia, the sodium level in the body is too low. The salts are then too diluted in the blood due to the increase in circulating blood volume. Symptoms primarily involve central nervous system dysfunction, leading to seizures, coma, or even death. Polycystic kidney disease, for its part, is a rare and incurable genetic disease. Cysts form in the kidneys and destroy their functioning, which end up having to be transplanted.

But how would this substance work on these two diseases? The toxin particularly selectively blocks receptors in the kidneys responsible for water homeostasis in the body. When the body needs water, during exercise for example, it concentrates urine to extract as much liquid as possible. It is this process which is stopped by the molecule synthesized by Nicolas Gilles. In the case of hyponatremia, by blocking the receptor, the patient can eliminate water via urine, without losing salt, and thus regain normal sodium levels. For polycystic kidney disease, V4C-232 slows the progression of the disease and therefore delays transplantation.

The creation of the start-up, a great adventure

After discovering this molecule with great potential, Nicolas Gilles conducted molecular pharmacology and in vivo tests on rodents to validate the biological activity of this toxin. It thus demonstrates the effectiveness of this substance in treating kidney pathologies. He then improves it to give it more activity. Following his work, he filed a patent and decided to go further in the development of this drug candidate by creating a start-up.

Initially, the researcher wanted to find a pharmaceutical industry able to take its active ingredient in order to develop it. Finally, he worked for almost a year and a half with a company in Lyon. Unfortunately, the latter leaves the project, which motivates Nicolas Gilles to set up his own start-up. But for this, he needs the help of a CEO who can support the rise of the start-up. He then met Sonia Escaich, an expert in pharmaceutical R&D and the creation of biotechnologies, in 2022. For the next 18 months, they worked together to consolidate the business plan, the strategy, and make presentations for business angels. Thanks to the support of the CEA via the Magellan program, they carry out a market study and competition conditions, in order to be certain that their drug candidate has a place on the market. After so much effort, the start-up, called V4Cure, was created in March 2023. Nabil Gharios, a finance specialist who manages investment funds in biotechs, came to consolidate the team.

In 2022, V4Cure was the winner of the i-Lab jury grand prize, benefiting from an innovation grant. In February 2023, several business angels financed it to the tune of 500,000 euros. Now that the molecule is finalized and optimized, this money will make it possible to work on the formulation of the drug candidate, that is to say the way in which it will be administered. Next November, the start-up will start a new fundraising for a series A. The founders of the company hope to begin phase I trials in 2026 and a phase II in 2027. These stages completed, the start-up will be sold to a large pharmaceutical company which will be responsible for carrying out phases III and putting it on the market by 2032.

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