The disease’s incidence and prevalence are steadily increasing in most analyzed geographies, making it a major public health issue. By 2035, the number of diagnosed prevalent Crohn’s disease cases in the US, Japan, France, Germany, UK, Spain and in Italy, is expected to increase by 16.9% and reach 1.6 million.
The large rise in Crohn’s disease prevalence is due to 2 main factors:
In other words, with incidence outpacing death, patients with newly diagnosed Crohn disease are continually added to the pool of prevalent patients, leading to the compounding prevalence of Crohn’s disease over time.
Crohn’s disease still lacks curative treatment. Yet, there are over a dozen existing treatments for Crohn’s disease, mainly immunosuppressors aiming at lowering the immune system response, and with it the inflammation, but with very serious unwanted consequences when administered on a long-term basis (increased cancer and infection risks). Drugs mainly aim at reducing symptoms during flares, artificially inducing remission. Such a remission does not last for long unfortunately, resulting in patients living in the fear of the next (and often more severe than the previous) flare. To this day, clinicians are still trying to discover an adequate therapy to maintain Crohn’s disease patients in remission for long periods of time without putting at risk their safety. This unmet medical need and the level of expectations from patients and physicians is particularly visible in the vitality of current research in this field. Indeed, 79 ongoing phase 2 or 3 clinical trials in Crohn's disease are registered on clinicaltrial.gov.
Rather than lowering the patients’ immune defenses with another immunosuppressive treatment, our approach is to improve the communication between the patient’s microbiome and their immune system, without inhibiting it. To do so, we will simply release a key naturally occurring gut bacterium, dominant in healthy subjects’ microbiomes, in the gut of patients. We believe that the F. prau strain that will be administered through EXL01 will send anti-inflammatory signals to the immune system sufficient to counterbalance the pro-inflammatory signals it receives from an unbalanced microbiome, thus stopping the vicious circle that leads to uncontrolled inflammation.
Crohn’s disease patients present an unbalanced microbiome (also called dysbiosis) that affects the communication between their immune-systems and their guts. Miscommunication between the microbiome and its host will trigger inappropriate immune responses leading to inflammation when there should not be. Indeed, an unbalanced microbiome will send more pro-inflammatory signals than anti-inflammatory ones. The immune system will therefore trigger a defensive response that translates into inflammation. Repeated and uncontrolled inflammation events will eventually cause the depletion of the good bacteria that generally send the counterbalancing anti-inflammatory signals – F. prau being the most representative one - thus leading to a vicious circle that characterizes this chronic condition.