Valérie Crépel, 2022 Innovation Prize

In less than a decade, neurobiologists Valérie Crépel from Inserm and Christophe Mulle from CNRS have brought a gene therapy for temporal lobe epilepsy to the stage at which it can soon be tested in patients. This success in creating industrial value has earned Valérie Crépel the Innovation Prize.

Frontal lobe epilepsy: gene therapy in our sights

Portrait de Valérie Crépel
Valérie Crépel, 2022 Innovation Prize – unit 1249 Inserm/Aix-Marseille Université, Marseille ©Inserm/François Guénet

Temporal lobe epilepsy is the most common form of epilepsy in adults. In 2005, Valérie Crépel, Inserm research director at the Mediterranean Institute of Neurobiology (Inmed) in Marseille, discovered that kainate receptors (KARs) of the neurotransmitter glutamate were involved. Seven years later, Crépel and Christophe Mulle, from the Interdisciplinary Institute of Neuroscience (IINS) in Bordeaux, demonstrated KARs to be a key element in the origin of this epilepsy in the hippocampus and furthermore a potential therapeutic target in a condition where 30% of patients are refractory to the available treatments. « I wanted us to protect this innovative data, » explains Crépel. So I contacted Inserm Transfert. » Thanks to this private subsidiary of Inserm that assists its scientists in creating value from their work, the two researchers filed a patent in September 2013.

Portrait de Christophe Mulle
Christophe Mulle, Institut interdisciplinaire de neurosciences (IINS), Bordeaux
©Inserm/François Guénet
Portraits des membres de l'équipe de Valérie Crépel
Alexandre Vigier, Célanie Matringhen, Thomas Marissal,
Céline Boileau, Delphine Pinatel, Édouard Pearlstein,
Lucas Goirand-Lopez et Nicolas Partouche ©Inserm/François Guénet

Two brains pitted against epilepsy

« Then we got lucky, she continues. In April 2014, Christophe presented our findings to venture capital companies that were looking at projects at Bordeaux Neurocampus. Kurma Partners expressed interest and asked us to consolidate our data. » So the two scientists validated the benefit of KAR inhibition and selected their therapeutic strategy, which was gene therapy. This involved preventing the synthesis of KARs in the cells of the hippocampus by providing them with microRNAs, which are short non-coding RNA sequences that control the expression of certain genes. Project maturation could then begin. « By identifying and structuring industrial collaborations, Vanessa Malier from Kurma Partners was one of the key drivers of the project, » emphasizes Crépel. Inserm Transfert and the Aquitaine Tech transfer acceleration company (SATT) funded it, managed the patents, transactions, etc., and gave us a lot of guidance. We had to quickly learn the codes of industry. » And for good reason, given that in 2017 everything took off. The US company Regenxbio, which specializes in gene therapy vectors – the « vehicles » that transport the therapeutic gene into the cells to be treated – joined the project. After 15 months of intense collaboration, the neurobiologists provided the proof of concept of a gene therapy for epilepsy. A new patent was filed. The start-up Corlieve Therapeutics was founded in November 2019 by Kurma Partners, which financed it with Eurazeo Investment Manager. Crépel and Mulle were its scientific co-founders, Inserm Transfert and the SATT, shareholders. Vanessa Malier, head of the board of directors, recruited R&D expert Richard Porter as CEO.

A start-up sold for a fortune

In 2021, the start-up embarked on a quest for investors. « Which was both a learning experience and difficult because it is not something that we are familiar with as researchers, » acknowledges the neurobiologist. But it turned out to be short-lived. On June 22, 2021 there was a spectacular turn of events: Corlieve Therapeutics became a subsidiary of Dutch biotech uniQure for… 250 million euros! This success story, honored by the Innovation Prize awarded to Crépel, is expected to lead to the treatment being evaluated in patients within one to two years. « It’s the Holy Grail of any researcher. So despite the work that the value creation involved, if I could do it again, then I would! » concludes the researcher.