Consortium

Academic partner

The Lamers group (LUMC-CCB) is lead by Dr. Meindert H. Lamers who is the expert in structural biology of macromolecular assemblies by protein crystallography and cryo-electron microscopy with a long experience in protein expression and purification, including protein expression of the non-pathogenic mycobacterial host Mycobacterium smegmatis. The Lamers group provides expertise in biochemical and biophysical characterization of macromolecular processes.

The LUMC Infectious Diseases (LUMC-ID) is represented by Prof. Tom H.M. Ottenhoff and Dr. Mariëlle C. Haks. LUMC-ID has established an internationally well recognized and competitive research program in the field of human immunology, cell biology and immunogenetics of mycobacterial infectious diseases. It discovered the first specific antigens for mycobacterium reactive T cells in humans, identified the first T-helper-1 cells in humans, discovered a new human immunodeficiency due to genetic mutations in the receptor for interleukin-12, cloned the first monoclonal T-regulatory cells in humans, and has been involved in many human genetic studies that identified multiple new genetic variants impacting on risk of tuberculosis and leprosy.

EFPIA partner

Collectively, Janssen R&D and its affiliates represent the worldwide pharmaceutical division of Johnson & Johnson, specialized in research into small molecules and biologics and is part of the world's largest healthcare company. Within the Johnson & Johnson group, Janssen Pharmaceutica NV is a worldwide Center of Excellence for integrated R&D, production and general services. In Europe, the main research facilities for Janssen Research & Development are in Beerse, Belgium, with research focused around the therapeutic areas of neuroscience, oncology, infectious diseases and immunology. Janssen’s initiatives in global public health complement the ground-breaking science of the Janssen Pharmaceutical Companies of Johnson & Johnson with innovative strategies that improve access to medicines, foster collaborations and support public health solutions to sustainably advance healthcare worldwide. Key focus areas include multi-drug resistant tuberculosis (MDR-TB); HIV; neglected tropical diseases (NTDs) such as elephantiasis, river blindness and intestinal worms; and use of mobile technologies (mHealth) to improve health outcomes. They work every day with the goal to discover and develop novel therapeutics and vaccines to treat and cure infectious diseases worldwide, improving treatment outcomes and patients’ lives.

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EFPIA partner

LUMC is a university medical center for research, education and patient care with a high-quality profile and a strong scientific orientation. It has a unique research practice, ranging from pure fundamental medical research to applied clinical research. Researchers at LUMC work together around 7 medical research profiles: Vascular and Regenerative Medicine; Immunity, Infection and Tolerance; Translational Neuroscience; Cancer Pathogenesis and Therapy; Ageing; Innovation in Health Strategy and Quality of Care; and Biomedical Imaging. LUMC is a center for medical innovation, committed to the advancement of health care and education in line with the latest international insights and standards - and aims to play a nationally and internationally recognized leading role in improving medicine and the quality of health care.

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Academic partner

University Antwerp

The University of Antwerp (UAntwerpen) is a fully accredited Belgian University with high standards of research and education. UAntwerpen is ranked 14th in the World, 7th in Europe among the “young” universities (less than 50 years of age) and 210th among all universities according to QS World University Rankings 2018. Although UAntwerpen is a mid-size university in Belgium, the CWTS Leiden Ranking in Natural Sciences ranks UAntwerpen 1st in Belgium in collaborative publications and 3rd in the category impact.
The Uantwerp is represented by 3 groups (LMPH, ORSY and UAMC) in RespiriTB and 2 groups (ORSY and UAMC) in RespiriNTM projects.

LMPH (The laboratory for Microbiology, Parasitology and Hygiene) represented by Prof. Paul Cos & Dr. Davie Cappoen & Prof. Peter Delputte adds to the consortium their prior knowledge and experience with mycothione reductase as mycobacterial target protein. The LMPH will be predominately involved in the target characterization, structural biology and development of potential inhibitors for mycothione reductase (Mtr).

ORSY (The Organic Synthesis) managed by Prof. Bert Maes & Prof. Wouter Herrebout will bring in their expertise in synthetic organic chemistry, in particular homogeneous transition-metal catalysis, heterocyclic and organometallic chemistry, as well as mechanistic studies. Further important assets are the available expertise in computer modelling provided by the Molecular Spectroscopy group used for prediction of spectroscopic data and the elucidation of the mechanisms of organic reactions, e.g. transition metal-catalyzed reactions, towards rational optimization of the reaction conditions.

UAMC (Medicinal Chemistry at the University of Antwerp) is led by Prof. Koen Augustyns, Prof. Pieter Van der Veken & Prof. Hans De Winter. This research group has a strong international track record in medicinal chemistry with focus on the therapeutic domains of infectious diseases, inflammation and cell death/survival. Their mission is to develop chemical tool compounds that are used in the characterisation and validation of novel targets, and that will lead to novel hit and lead compounds in drug discovery programmes.

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Academic partner

Sorbonne University

Sorbonne Université hence becomes a fully multidisciplinary research-intensive university with three faculties: Humanities and Social Sciences, Medicine and Sciences & Engineering. With more than 53 400 students (among 10 200 international students), 4400 doctoral students and 6300 researchers, Sorbonne Université is a leading French university. It assists the researchers for all the administrative, financial and legal aspects of the research projects. In particular, the research officers ensure a follow up of the project results and their adequate exploitation and technology transfer.

The Sorbonne group is leading by Dr. Vincent Jarlier & Dr. Nicolas Veziris and Dr. Alexandra Aubry. The group brings to the consortium a large medical and biological expertise on mycobacteriology, including M. tuberculosis and non-tuberculous mycobacteria (NTM) of medical importance, as well as the vision of therapeutic applications. The team focuses mainly its activity on therapeutic aspects of tuberculosis and NTM infections: (a) study of new drugs, based on microbiological technics, molecular biology, biochemistry and structural biology; (b) in vivo activity and efficiency of new therapeutic regimens using various mouse models; (c) mechanisms of resistance in clinical strains and in vitro selected mutants, based on microbiological technics, molecular biology (sequencing, WGS…) and biochemistry.

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Academic partner

Medical University Vienna

The Medical University of Vienna is the largest medical organization in Austria, as well as one of the top-level research institutions in Europe and provides Europe's largest hospital, the Vienna General Hospital, with all of its medical staff. It consists of 31 university clinics and clinical institutes, and 12 medical-theoretical departments, which perform around 48,000 operations each year. The Vienna General Hospital has about 100,000 patients treated as inpatients and 605,000 treated as outpatients each year. In the 2014–15 Times Higher Education Rankings, the Medical University of Vienna is listed among the top 15 medical schools in Europe and 49th in the world.

The Department of Clinical Pharmacology of the Medical University of Vienna is an academic institution which aims at providing expertise and special infrastructure on preclinical and clinical drug development with the ultimate goal to develop and evaluate innovative therapeutic interventions and diagnostic technologies. The department performs 30 phase 1 studies per year including several FIM studies. During the RespiriTB/NTM projects, the Department of Clinical Pharmacology of the Medical University will be represented by Prof. Markus Zeitlinger.

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Academic partner

University Copenhagen

University of Copenhagen is the largest and oldest university in Denmark and one of the oldest researches and teaching institutions in Northern Europe. The 38.000 students and 9.700 employees (of which more than 5000 are researchers) work on four large campus areas in Copenhagen. The University consists of 6 faculties consisting of 36 departments and more than 200 research centers. The University of Copenhagen is ranked as #22 in Europe and #73 in the world, according to QS World University Rankings 2017.

UCPH group directed by Dr. Anette Müllertz and Prof. Thomas Rades Will be responsible for the physico-chemical characterization of the lead compounds identified by the other partners and Jansen. This will include solubility and supersaturation propensity of the lead compounds. Based on the outcome, a formulation strategy will be formed. Drug delivery systems will be developed using physiological relevant in vitro models simulating the GI tract. Both lipid-based and amorphous delivery approaches will be considered for developing the most suitable formulation for increasing the bioavailability. Selected drug delivery systems will be tested for their pharmaco-kinetic profile in small animal models.

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Academic partner

Leiden University

Leiden University was founded in 1575 and is one of Europe’s leading international research universities. It has seven faculties in the arts, humanities and sciences, spread over locations in Leiden and The Hague. The University has over 6,700 staff members and 28,130 students. Much of our research focuses on making the unknown known and extending the boundaries of existing fields of research. Our research has a strong disciplinary basis within a very broad range of scientific fields. The university has thirty research institutes, located in both Leiden and The Hague, each of which conducts disciplinary and interdisciplinary research. Our researchers maintain close contacts with one another other and with society across the boundaries of their institutes and faculties. They are guided by the highest ambitions of quality and integrity.

Leiden group leader, Prof. Herman P. Spaink is the experts in the use of cell biology and systems biology and pharmacology to test efficacy and pharmacokinetic properties of drugs against infectious disease. For this we use as well high throughput experimental approaches as theory development to translate data from different test systems. A major focus has been on testing antibiotics in tuberculosis disease models, with a main emphasis of the responses of the pathogens inside the host immune cells. This is highly relevant since pathogens have a very different response to drugs when they are inside the host as compared to the free-living state. One of our major systems models for tuberculosis progression is the use of zebrafish larvae for high throughput screening.

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SME partner

Mitologics

Mitologics SAS is an innovative French biotechnology company (SME) founded in 2009 by Dr. Annie Borgne-Sanchez, Dr. Nelly Buron and Mathieu Porceddu. The company is specialized in the detection of mitochondrial alterations for applications in toxicology and pharmacology. The team has a strong expertise in cell and mitochondrial biology, metabolism, apoptosis and cancer. The company won the “Concours national d’aide à la creation d’entreprises de technologies innovantes” in 2009 and 2011, awarded by the French Ministry of Education and Research. Mitologics is member of the “Pôle de Compétitivité MEDICEN Paris-Région” and of the French association of R&D service providers participating to innovative research programs in Life Sciences (AFSSI).

Mitologics directed by Dr. Annie Borgne-Sanchez will evaluate compounds provided by partners of the consortium for their mitochondrial toxicity risks on its screening platform (MiToxView®). Both acute and long-term mitochondrial toxicity will be studied on isolated rodent mitochondria (first stage screening) and hepatic differentiated cells (on optimized compounds). Mitologics has published several papers validating its screening assays to detect drug-induced mitochondrial damages and performed several studies for pharmaceutical and cosmetic industry.

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SME partner

FFUND

FFUND is a young and ambitious Dutch SME that provides full-service consultancy in project management, assistance in development of exploitation strategies, active communication, dissemination and promotion activities, based on years of experience. We combine scientific expertise and in-depth knowledge of project management with translational science and life science entrepreneurship. FFUND is able to identify exploitable research results, and support scientist in defining the optimal strategy for valorisation. Moreover, FFUND is expert at securing the right (non-) dilutive funding for R&D projects.

During the RespiriTB/NTM projects, FFUND’s PRINCE qualified project manager, Dr. Mima Malcicka, will aid in management and developing dissemination strategies. Moreover, FFUND plans for success continuation of the technology by securing follow-up funding throughout the complete value chain from the early start, through controlled growth, until a successful exit. FFUND will ask the tough questions to clear up any ambiguities and spot the innovative strengths, ultimately leading successful commercialization of the RESPIRI-TB results.

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