Development of Human epithelial cellular models for predictive and pharmacological testing in dry eye diseases (DED) – DED-Line

The STIM laboratory (University of Poitiers) and H4 Orphan Pharma a Dijon-based pharmaceutic company will create the common laboratory DED-Lab to develop a new R&D axe in ocular area and in particular in Dry Eye Diseases (DED). Pr Frédéric Becq for the laboratory and Dr Gaëtan Terrasse for the society will coordinate this ANR Labcom project DED-Line. A directory committee will define the scientific and economic perspectives.
An innovative project for solving the scientific and technical locks due to the absence of predictive Human DED cellular models: DED is a multifactorial malady of the tears and ocular surface that results in symptoms of discomfort, visual disturbances and tears film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of tear film and inflammation of the ocular surface. It affects millions of patients worldwide with no efficient treatment so far. There is thus an urgent unmet need for DED. The market size is estimated to 4.6-6.2 billions$ for the period 2018-2023, including medicines, medical devices and companion tests. The DED-Line project will put in synergy our respective complementary scientific and entrepreneurial expertises to develop Human DED cellular models in order to study in vitro novel therapeutic pharmacological agents and concepts. A network of ophtalmologists, already contacted, has confimed its interest for the project and its perspectives. DED-Line will also be fueled by recent progresses made by STIM laboratory and H4 Orphan Pharma identifying the potential of 2 small compounds (554-001 and 554-002) as CFTR ion channel agonists. DED-Line project will be more ethic, due to the absence of animal model experiments in our research. We thus aimed to lift scientific and technical locks and barriers by creating ocular Human DED cell cultures, mimicking DED, allowing their biobanking, dissemination and use to screen on-demand chemicals and to define the mechanism of action of our own lead compounds.
A leading project for both partners : The DED-line ANR project is perfectly adapted and equally important for the research axes of STIM laboratory and for the R&D of H4 Orphan Pharma. H4 Orphan Pharma is indeed developing novel therapeutic concepts with the goal to exploit for the company itself and through licensing out processes, discoveries at the preclinical and clinical stages. STIM laboratory has a 30 years expertise in epithelial ionic transport, pharmacology and preclinical development of ion channels modulators. The DED-Line project will strengthen the second axe of the company R&D and will help to positioned STIM laboratory at the frontline, in France and Europe, of research in DED and ocular physiopathology.
A team project of 15 memberss for a total of 314 men-month on 54 months: At the start of our project the team will be built by 10 members of the STIM laboratory including two technical staff members on ANR funding and 5 members of H4 Orphan Pharma including two peoples to be recruited by the company (not on ANR budget).
Perpetuation of the project : Our major research axes will conduct both partners to continue their collaboration through new projects and graduate students (CIFRE fellowship in 2025) to strengthen our research effort. The partners will search for additional resources and funding (local, national and international). The starting team will enroll additional experts in clinical development, clinical trials, regulatory affairs as well as new technical staffs. Finally the objectives of the future DED-Lab in 2025 will be (1) the drug screening with our patented cellular models to discover new small chemicals of therapeutic interest, (2) the development and commercialization of a “kit of analysis” for innovative molecules for our future clients, (3) the therapeutic development of our lead compounds (in particular our patented 554-002 compound).