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Nematic protein organisation technology:

Nematic protein organisation technology: A powerful tool to track drugs toxicity and side effects already at early preclinical drug development. 3 rd International summit on Toxicology & applied Pharmacology. Inoviem Scientific – an observation. Today’s drug development.

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Nematic protein organisation technology:

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  1. Nematic protein organisation technology: A powerful tool to track drugs toxicity and side effects already at early preclinical drug development 3rd International summit on Toxicology & applied Pharmacology

  2. Inoviem Scientific – an observation Today’s drug development Light at the end of the tunnel Opening Confidentiel

  3. No issue Due to toxicity and lose of efficacy from pre-to clinical studies Confidentiel

  4. or opening Confidentiel

  5. Drug candidat or a ligand

  6. InoviemScientific – Une force Inefficiency

  7. inefficiency cure

  8. Inoviem’sapproach R&D Preclinical Phase Preclinical Phase Clinical Phase Market Classicalin vitro techniques Classical Molecule HumanBeing/ Patient R&D Preclinical Phase Market Inoviem Molecule Animal HumanBeing/ Patient Animal HumanTissue (1µg) Healthy or from patient Risque 100 0 Non-confidential

  9. Our technologies PIMS :Physiological Intermolecular Modulation Spectroscopy NPOT: Nematic Protein Organisation Technology MUXI : Multiplex ‘Cross-Sandwich’ Immunoassay • In Practice : • From as low as 1 µg of a tissue, we pinpoint the target of your compound in each organ Non-confidential

  10. Fromcrudehuman tissue to therapeutictarget Lead or drug Human tissue Extract PIMS: Visualising Discriminating NPOT: Isolating Identifying MUXI: Reconstructing in 3D Representing Non-confidential

  11. • Isolation and identification of therapeutic target • « hit » to « lead » discrimination ON Target • Target identification ( ) Preclinical • Toxic target identification ( ) OFF Target • Lead optimisation Our services InoviemScientificbringsits expertise in the process of drugdevelopment and offer a full range of tailored services : • Biomarker identification Non-confidential

  12. • Pre-phase II patients stratification & optimisation for phase II clinical trial • Drug rescue Clinical • Drug-up: optimisation of ON/OFF target interaction ratio Individualized medicine: Post market patient stratification to responders • and non-responders Individualized medicine: Biomarker identification, validation and selection & • associated companion test development Our services InoviemScientificbringsits expertise in the process of drugdevelopment and offer a full range of tailored services : Non-confidential

  13. Dynamic and Static Non-confidential

  14. Theory and biology A * B = B* A O2 * H2 = H2 * O2 = * * ≠ * * Non-confidential

  15. Fromorder to disorder & miss-order Equilibrium missorder t=1 Equilibrium t=0 Disorder ΔGD > ΔGE0 = ΔGE1 Non-confidential

  16. From miss-order to distorted order Equilibrium t=1 1st Disorder Distorted order ΔGD1 < ΔGD2 > ΔGE1 Non-confidential

  17. The very same molecular composition Solid Stable state physiologic Meta-Stable state solid Meta-Stable state >45°C 22°C -20°C Non-confidential

  18. Physiology and pathology Non-confidential

  19. Life’s philharmonic Non-confidential

  20. Requirements for maiintenance of physiological conditions Dynamic Environment specific Take into account order of molecular interaction Take into account the impact of a disruption Take into account molecular energy state Non-confidential

  21. Our technologies PIMS : Physiological Intermolecular Modulation Spectroscopy NPOT: Nematic Protein Organisation Technology • In Practice : • From as low as 1 µg of a tissue, we pinpoint the target of your compound in each organ Non-confidential

  22. Nematicprotein organisation technique Nematic crystals Drug Hetero-oligomersation Specific macromolecular assembly Non-confidential

  23. Examples NPOT Identifies a drug or a xenobiotic target & its partners in a physiological condition. Non-confidential Atropine Serotonine Solvent Putamen Cerebellum Prefrontal cortex

  24. Examples NPOT Identifies a drug or a xenobiotic target & its partners in a physiological condition. Small molecule Compound 1 Compound 2 Compound 3 Lead Solvent Peptide Non-confidential

  25. Macromolecular auto -assembly of total human placenta Membrane with recombinant TGFβ (rTGFβ) In absence of rTGFβ In presence of rTGFβ Macromolecular assemblies due to the presence of 1µl of rTGFβ is shown with blue arrow. In absence of rTGFβ no macromolecular assemblies are formed Non-confidential

  26. Schematicrepresentation of familyrTGFβmolecular interaction Receptor partner 2 rTGF-βfamily Proton pump Receptor partner 1 Spectrin beta non- erythrocytic G-actin Receptor partner 3 Destrin Non-confidential

  27. A NPOT: a highly reproducible, rapid and safe technique for isolating & identifying drugs’ ON/OFF targets • Prot. 1 • Prot. 2 • Prot. 3 • … Identification Extracted Specific ON/OFF Targets Isolation Proteomics Non-confidential

  28. Demonstration of concept Clozapine Identified On Target Identified OFF Target Molecular Design Original molecules Partner (Leponex) Charité Berlin LabEx Hydroxychloroquine (Plaquenil) Start 09/2012 Patent application 03/2013 Non-confidential

  29. DRUG UP PATHOLOGY: LUPUS Treatment: Hydroxychlorquine (HCQ) • Clinical efficacy of HCQ: • About 30% responder with no vasculitis, skin & joint inflammation • Retinopathy with chronic treatment Clinical study PBMCs from 20 patient all on HCQ and subjected to NPOT Non-confidential

  30. RU CB133 HCQ 50 40 30 20 10 Response 0 -10 -20 -30 -100 0 100 200 300 400 500 Time s OFF Target

  31. RU CB029 70 50 30 Response 10 -10 -30 -100 0 100 200 300 400 500 Time s

  32. CB072

  33. RU CB103 50 40 30 20 Response 10 0 -10 -20 -100 0 100 200 300 400 500 Time s

  34. RU CB108 40 30 20 Response 10 0 -10 -20 -100 0 100 200 300 400 500 Time s

  35. RU CB112 25 20 15 10 5 Response 0 -5 -10 -15 -100 0 100 200 300 400 500 Time s

  36. RU CB114 60 40 20 Response 0 -20 -40 -100 0 100 200 300 400 500 Time s

  37. RU CB133 HCQ 450 350 250 Response 150 50 -50 -100 0 100 200 300 400 500 Time s ON Target

  38. RU CB029 1000 800 600 400 Response 200 0 -200 -100 0 100 200 300 400 500 Time s

  39. RU CB072 160 140 120 100 80 Response 60 40 20 0 -20 -100 0 100 200 300 400 500 Time s

  40. RU CB103 1200 1000 800 600 Response 400 200 0 -200 -100 0 100 200 300 400 500 Time s

  41. RU CB108 400 350 300 250 200 Response 150 100 50 0 -50 -100 0 100 200 300 400 500 Time s

  42. RU CB112 180 130 Response 80 30 -20 -100 0 100 200 300 400 500 Time s

  43. RU CB114 600 500 400 300 Response 200 100 0 -100 -100 0 100 200 300 400 500 Time s

  44. Innovation – more than just a word From preclinical to clinical: Leading explorer of drug-target interaction Inoviem Scientific (ISIS) 8 Rue Gaspard Monge F-67084 Strasbourg Siège social: INOVIEM SCIENTIFIC SAS 8, rue de Verdun F-67084 Strasbourg Tel: 03 68 85 14 38 www.inoviem.com Inoviem Scientific (IPCB) 15 Rue René Descartes F-67084 Strasbourg Non-confidential

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