V4Cure: snake venom to treat kidneys
Inspired by a toxin found in the venom of the mamba, a venomous snake from Africa, V4Cure, a start-up based in Ile-de-France, is developing a drug candidate designed to treat two kidney diseases that are poorly treated by current pharmacopoeia. Focus on this promising, new company.
In March 2023, Nicolas Gilles, a researcher at the French Alternative Energies and Atomic Energy Commission (CEA) and future CEO Sonia Escaich set up V4Cure. This start-up originated in the Laboratory of Experimental and Molecular Pharmacology (LPEM) of the Molecular Engineering for Health Unit (SIMOS), which is part of the Medicines and Healthcare Technologies Department (MTS - Université Paris-Saclay, CEA, French National Research Institute for Agriculture, Food and Environment INRAE). It is accommodated by the BPS start-up incubator at the Cochin Hospital in Paris. Its aim is to develop a drug candidate called V4C-232. This is a derivative of a toxin contained in the venom of the mamba, a sub-Saharan African snake whose bite is fatal to humans. This molecule could be used to treat two diseases - hyponatremia and polycystic kidney disease - which affect ten million people in the West.
In hypervolemic hyponatremia, sodium levels in the body become too low due to an excess of total body water. The salts then become too diluted in the blood. This electrolyte anomaly mainly involves a dysfunction of the central nervous system, leading to epileptic seizures, coma or even death. Polycystic kidney disease is a rare and incurable genetic disorder. Cysts form in the kidneys destroying their function leading to a need for a kidney transplant in affected patients.
A highly selective toxin
"Our toxin selectively blocks the kidney receptors responsible for water homeostasis in the body. For example, when we exert ourselves, we sweat and our body needs fluids so it concentrates the urine to extract water. Our molecule stops this process. 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. In polycystic kidney disease, the V4C-232 molecule slows disease progression and thus delays the need for a transplant," explains Nicolas Gilles, founder of V4Cure.
This promising molecule is the result of Nicolas Gilles' long-term work in the laboratory since 2009. "For years, I've been studying animal toxins to try and discover therapeutic candidates. I set up a strategy to identify therapeutic targets and develop screening tests to identify animal toxins of interest. Of all the substances identified, the one of greatest interest was 'mambaquaretin', found in the venom of the eponymous snake, which blocks urinary concentration without causing salt loss," explains the researcher. He subsequently conducted molecular pharmacology and in vivo tests on rodents to validate the toxin's biological activity. "I demonstrated the efficacy of this molecule in treating kidney disease. I then improved it to give it more activity." Following his work, the researcher filed a second patent (PCT/EP2021/0672248). "The only strategy to take the development of this drug candidate even further was to create a start-up."
A start-up to drive development
Nicolas Gilles' initial plan was to find a pharmaceutical company capable of taking his active ingredient and developing it. He worked with a Lyon-based company for almost a year and a half. Unfortunately, this company abandoned the project, which led Nicolas Gilles to create his own start-up. "I was looking for a CEO who would be able to take responsibility for the start-up's development and it was at this point, in September 2022, that I met Sonia Escaich, an expert in pharmaceutical R&D and biotech creation. We then worked together for over eighteen months to consolidate our business plan and strategy and make presentations to business angels. Thanks to the support from the CEA via the Magellan programme, we were able to conduct market research and assess competition conditions. We had to be sure that there was a place for our future drug candidate. We interviewed nephrologists to find out whether our treatment would be well received. We also had to talk to various contacts to be sure that we could raise the money. In the end, we officially created V4Cure in March 2023," explains Nicolas Gilles. Four founders are behind the company: CEA, Nicolas Gilles, Sonia Escaich and Nabil Gharios, a finance specialist who manages investment funds in biotech.
V4Cure, i-Lab 2022 grand prize winner
In 2022, V4Cure won the i-Lab Grand Prize and received this innovation grant. As Nicolas Gilles explains, "in January and February 2023, we talked to business angels who financed us with an additional €500,000, which helped us to unlock the i-Lab funds. Now that the molecule has been finalised and optimised, this money will enable us to work on the formulation of the drug candidate, in other words, how it will be administered.” Meanwhile, the market research is continuing for a better understanding patient needs. In November 2023, the start-up will launch a new round of Series A financing and by the end of the year, V4Cure should also benefit from further support for the creation of innovative companies from the BPI. Eventually, it wants to recruit between five and seven people.
The company's founders hope to start phase I trials in 2026 and phase II in 2027. They will be assisted by service providers who will carry out studies as part of the therapeutic development. "After this stage, we will sell V4Cure to a major pharmaceutical company, which will carry out phase III trials and bring the drug to market by 2032," comments Nicolas Gilles.
Although the original toxin comes from the African green mamba, the drug candidate's molecule is entirely synthetic and recreated in the laboratory. "This shows how important it is to preserve natural resources. Right now, flora and fauna are still the greatest source of inspiration for drug development. In the venom of even the smallest spider, there are several hundred toxins that could be used to manufacture the drugs of the future," concludes the researcher.