Presentation

In December 2009, France issued a loan to fund the "Investments in the Future" programme with a €35bn commitment to sustain its future growth, out of which €22 Bn are devoted to research and higher education. In 2011, a first call for proposals led to the selection of 100 projects identified as "Laboratories of Excellence".

The Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT) is one of these 100 projects funded, and one of the 24 selected projects in Life Sciences. LERMIT has received a €19 Mn budget for the period 2011-2020.

LERMIT is an interdisciplinary laboratory composed of high-profile biologists, chemists and physico-chemists joining their forces to collectively explore new therapeutic avenues. Our common goal is to combat three major classes of diseases presenting a continuous threat to the society: cancer, cardiovascular diseases, and infectious and immune diseases. To achieve this goal, our joined effort will be directed towards :

• a better understanding of the molecular mechanisms causing these diseases ;
• the discovery of new therapeutic targets ;
• the design and development of new medications to treat - or block the progression of - these diseases ;
• the development of new strategies for improved targeting and delivery of the medications at the disease site ;
• an improved efficacy of current therapeutics.

Graduate students and young employees from biotech companies and pharmaceutical industries will be exposed within LERMIT to cutting-edge research developments in drug discovery and therapeutic innovation through unique interdisciplinary training courses. Besides maintaining the highest standards of academic research, LERMIT will generate intellectual property (IP) and value its IP by providing sufficient support for technological maturation and development to generate profit. Effort towards any given new therapeutic strategy will be supported within LERMIT until the preclinical or phase I/II clinical stage. Spin-off biotech companies from LERMIT partners or big-pharma companies will take over at this stage.

To this aim, LERMIT capitalizes on a unique combination of expertise present within 15 partner laboratories (37 teams, >500 persons) in biology/medicine, biology/chemistry, medicinal chemistry, physico-chemistry and pharmaceutical sciences. Research topics covered by the biology/medicine partners concern cardiovascular diseases, inflammation and immune deficiency, infection diseases and cancer. Research topics covered by the chemistry and physico-chemistry partners include organic synthesis (green and ecocompatible chemistry), extraction and purification of natural products, modelling, imaging, pharmaceutical sciences, nanomedicine and drug delivery. These partners are currently located within 0-30 km distance from each other, in the southern Paris suburbs, and have the objective to move closer for a large majority of them by relocation on the new Paris-Saclay Campus.

The goal of LERMIT is thus to foster interdisciplinary research at the interface between chemistry, physico-chemistry and biology. Organizing the research around this main objective was not an easy task and required heavy brainstorming and stimulating discussions. As a result, we decided to organise the research within LERMIT around three main topics.

The first topic – TARGETS - aims at identifying and validating new therapeutic targets in the three classes of diseases listed above. This includes discovery of molecular mechanisms, proof of concept in cellular and animal models, screening of chemical libraries, validation and chemical optimization of the hits, preliminary ADMET and drugability tests, molecular modelling, evaluation of the lead molecules in animal models, etc. Three specific projects are proposed below to find new drugs to fight against 1) cardiovascular diseases (T1), 2) inflammation and immune deficiency (T2) and 3) cancer (T3).

The second topic – RESISTANCE - aims at identifying new strategies to get around the reduction in effectiveness of a drug in curing a disease. This concerns obviously the resistance to antimicrobial and anti-cancer drugs, but also more recently the resistance to immunotherapies. Resistance involves molecular mechanisms, such as mutation of the target enzyme or its relocation. Identifying these mechanisms allows a predictive structural pharmacological approach and the design of new and more efficient drugs. Two specific projects are proposed, one is to fight the antibiotic-resistant Gram-negative bacteria (R1), and the other to overcome biotherapy treatment failure in patients with rheumatoid arthritis (R2).

The third topic – DELIVERY – aims at designing new delivery systems, mainly nano and microtechnologies, to improve i) drug delivery to the right target and avoiding broad distribution that induce toxicity, ii) protection against degradation, and iii) drug transport across biological barriers. Because of a strong expertise within LERMIT in the field of cardiovascular diseases, we propose an innovative and ambitious interdisciplinary project to target the cardiovascular sphere and the pulmonary vasculature (D1).

One of the greatest challenges of LERMIT is to be able to move a discovery from bench to bedside. Our goal is that the technological advances made within the LERMIT consortium either will be transferred to small and medium-sized companies for industrial development, or will lead to the creation of start-up companies able to develop industrially the research carried out by public stakeholders within LERMIT.

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