Author: Maëva Gardet-Pizzo

Highlight: Although colossal, the pain market has not been particularly innovative in recent decades, despite the emergence of tragedies such as the opioid crisis in the United States. In Marseille, a company resulting from public research work (CNRS - Aix-Marseille University) intends to change the situation. It has developed a new family of non-opioid painkiller molecules, capable of treating all types of pain without side effects or tolerance problems. Human clinical trials are imminent.

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It can be acute or chronic. Worrying. Unbearable sometimes. Pain would in any case be the reason for two thirds of medical consultations in France, its chronic forms affecting one in three French people. On a macroeconomic scale, pain represents considerable expenses for the community. 300 billion euros annually for the European continent alone.

And the proposed remedies have many flaws. “The pain market has seen very little innovation in thirty years,” observes Eric Schettini, president of Tafalgie Therapeutics. For mild to moderate pain, paracetamol is the most used molecule but its misuse is frequent, and not without risks. As for intense pain, since the 1900s it has given rise to treatment using opioids, causing a huge health crisis in North America. A crisis causing 500,000 deaths in the United States since the 1990s. Including 120,000 in 2023 alone. The cause: the dependence generated by opioid-based treatments, which is growing in a socio-economic context unfavorable, many people compensate for the lack by turning to other drugs (heroin, fentanyl), sometimes in the context of particularly fatal cocktails. “There are two major problems with opioids. First, they induce hyperalgesia which means that the more you take, the lower the pain trigger threshold is. So we always need to take more. Then, a tolerance mechanism sets in: the more I take, the more I need to increase the dose to obtain the same effect. Hence the phenomena of addiction.” There is therefore an urgent need to propose an alternative. What Tafalgie Therapeutics is working on.

Rooted in public research Spin-off from CNRS and Aix-Marseille University, this company is developing a new generation of pain-relieving peptides not containing opioids. A breakthrough innovation which has earned the company one of the rare European companies to win the accelerator program of the European Innovation Council. An innovation born from a chance meeting between Eric Schettini and Aziz Moqrich, doctor in neuroscience. The meeting takes place in 2019. Eric Schettini comes from the world of investment. Interested in the biotechnology sector, he crossed paths with Aziz Moqrich and was sensitive to his history. “After a thesis in Marseille, Aziz worked for five years in the United States, notably in the laboratory of Ardem Patapoulian, 2021 Nobel Prize winner in medicine,” says Eric Schettini. Returning to Marseille in 2005, Aziz Moqrich decided to open his own laboratory, the Institute of Developmental Biology. He is then interested in the mechanisms of pain, the way in which information is transmitted and the proteins involved in this system. It was then that he discovered the TAFA4 protein, a protein secreted naturally in all mammals whose function is, in addition to inhibiting the intensity of the pain signal, to trigger a cascade of events capable of restoring normal functioning. normal cellular.

So this protein - as well as its derivatives - has potential in the treatment of pain, including chronic and acute. And this, without generating side effects or tolerance. Used to treat pain, this protein also has the virtue of preventing it. A major advantage in the context of surgery in particular, to avoid the onset of post-operative pain.

Clinical trials imminent This research is therefore promising. Except that in 2019, “Aziz Moqrich exhausted all public funding for fundamental research. He is stuck. We talked about it for four or five hours and I ended up convincing him to create a company to be able to promote the results of his research.” This is how Tafalgie Therapeutics was born. Combining public and private sectors, the company brings together a multidisciplinary team made up of clinicians, pharmacologists, but also specialists in law and research and development. “We negotiated with the CNRS, AMU and SATT Sud-Est to set up a collaboration contract and an exclusive license to exploit the patent filed in 2014 by the CNRS”

To date, the company - which managed to raise 15 million euros and benefits from the support of Bpifrance - has carried out all the preclinical stages, showing on animals (dog, rat, mouse), effectiveness similar to that of opioids. “We are on the eve of entering human clinical trials. We are quite optimistic about our ability to get through the first phase because the pain mechanisms are similar in all mammals. We look forward to testing the effectiveness: will it be as high as in animals? » The tests will first focus on a first candidate that is less advanced in terms of galenics and stabilization, in order to obtain proof of effectiveness as quickly as possible. “For this first candidate, we hope to have phase 2-A results by the end of 2025.” The second candidate will arrive later, for oral administration. Among the company's priority targets: post-operative pain which represents 24% of the pain market, and chronic pain of all types (45% of the market), particularly neuropathic pain which is currently not found Answer. Transforming into a center of excellence in pain For commercialization, we will probably have to wait until 2030. “But we hope to do better. If our compound has an effectiveness evaluated in animals, we think that the public authorities could accelerate the procedure because of the issues.” Tafalgie Therapeutics does not intend to take charge of this marketing itself. “The market is so colossal that we will have no other choice but to enter into licensing contracts with large groups.” The company, which is expected to expand to 35 people by the end of 2025 compared to 15 today, instead wishes to continue its research efforts. “We would like to expand our portfolio with other molecules that act according to the same mechanism and set up a center of excellence for pain.” However, the team is already asking itself the question of the price of its protein, and therefore its accessibility. “We are working hard on this subject, which relates to production methods. We favor bio-production rather than production by synthesis. This poses fewer problems with raw materials since we can produce billions of bacteria in one night and this is a strong expectation from the market which would also make it possible to offer lower prices.” Prices which should remain higher than those of opioids, but “with an incomparable benefit-risk ratio”.