The SPELITEC project aims at developing a first-in-class medicinal product to treat patients infected by Shiga toxin-producing Escherischia coli (STEC).
STEC bacteria primarily infect young children and are responsible for severe bloody diarrhea with serious complications (kidney failure, death). STEC outbreaks can have devastating consequences as seen with the German outbreak of 2011 that killed more than 50 people. Despite the severity of the disease, STEC infections remain an unmet medical need: antibiotics are contraindicated as they may favor the production of toxin by STEC bacteria and worsen the situation, and no other treatment strategy has been approved to treat this condition so far.
In this context the SPELITEC project aims at developing EB003, a new class of highly specific antimicrobial able to target and eliminate STEC bacteria while preventing the production of Shiga toxins. Such product will bring the following advantages to patients and society:
- It will eliminate STEC pathogens from the intestines of infected patients early in the course of the disease.
- It will display an excellent safety profile and its unparalleled specificity will leave all non STEC bacteria (including beneficial microbes from the microbiota) unharmed
- It will cure patients' bloody diarrhea and prevent the serious complications of the disease (kidney failure and death).
- It will reduce the risk of STEC outbreaks as the efficient elimination of the STEC pathogen in patients’ intestines will prevent its spread to the community.
To achieve this goal, the main objectives of the SPELITEC project were:
- To transition from a laboratory-scale to an industrial-scale production of the EB003 compound to meet clinical needs
- To confirm the efficacy of EB003 in various preclinical models in vitro and in vivo.
- To confirm the safety of EB003 in regulatory toxicology models
- To obtain validation from regulatory agencies to perform first clinical trials in humans.
At the end of the final period, we can draw the following conclusions for the SPELITEC project:
- the manufacturing process of the EB003 compound has been successfully transferred to a CDMO, with production of a 100L-scale batch in GMP-like conditions ;
- the efficacy of EB003 has been demonstrated in-vitro (killing experiments on clinical strains) and in-vivo (decolonization and symptom mitigation proven in various mice and rabbit models) ;
- the safety of EB003 has been assessed and confirmed in vitro (on eukaryotic cells through transfection studies) and in-vivo (preliminary and secondary GLP-like toxicology studies) ;
- interactions with regulatory agencies have helped us assess the regulatory requirements for EB003's entry in clinics, and confirmed the quality of EB003's preclinical package.
