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Mvid educational presentation 9-3-17

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Explains the pathogenesis of diarrhea in MVID in simple, easy to understand terms. Demonstrates that intestine does not fail permanently in MVID. Shows that the treatment options don’t end with Total Parenteral Nutrition (TPN) and transplantation.
This presentation is an educational resource, courtesy of Vanessa Research, Inc. © 2017. Shylicine™ is a registered trademark of Vanessa Research, Inc.

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Mvid educational presentation 9-3-17

  1. 1. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 MVID: On a Path To A Medical Treatment Dmitry Kravtsov, M.D.
  2. 2. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Vanessa Research: Who we are - 11 years of rare genetic diseases research at Vanderbilt and Yale - 4 years of MVID research - There is no tool to bring treatment to patients by doing research Research and Development Business Development - Drugs are developed by the companies, not universities - Over 30 years of business development in the biomedical areas Regulatory and Manufacturing - Over 10 years of experience with new drug development and applications - Pernix Pharma GMP drug manufacturing: 15 + years of experience.
  3. 3. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Research and Development Business Development Regulatory and Manufacturing Dmitry Kravtsov, M.D. Ludmila Kvochina, M.D., PH.D. Billy Chang, BS Nelson Chang, BS James Goldenring, M.D., PH.D. (advisory board) Henri Binder, M.D. (advisory board) Norman Gray, Sc.D. Ferenc Fazekas, M.B.A. Malna Polya, M.B.A. Zachary Robbins, B.S. Benjamin Szabo, J.D. Sandor Bernard, Ph. D., M.B.A. (consultant) Szabolcs Dobson, Ph.D. (consultant) Gabor Bakos, Ph.D. Vanessa Research: The core team
  4. 4. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 The scope of this presentation - Educational presentation - Explain pathogenesis of diarrhea in MVID in simple, easy to understand terms - Demonstrate that intestine does not fail permanently in MVID - Show that the treatment options don’t end with Total Parenteral Nutrition (TPN) and transplantation
  5. 5. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 What is MVID? • Microvillus Inclusion Disease (MVID) is a chronic, life-threatening SECRETORY DIARRHEA beginning in the first hours to days of life. No curative therapy exists and the current treatment options are poor with regard to long-term quality of life and survival. • It is an autosomal recessive disease caused by mutations in the MYO5B gene • The volume of stool-loss often exceeds the stool-loss in cholera. As a result, affected infants will die of dehydration and electrolyte abnormalities unless appropriate (often massive) intravenous fluid replacement is provided.
  6. 6. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Mechanism of Secretory Diarrhea
  7. 7. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Why is diarrhea dangerous? Source: https://www.slideshare.net/whiteraven68/6-acute-gastroenteritis
  8. 8. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 How dehydration kills? 70% of our body is a weak salt solution Remove water Source: http://laughingkidslearn.com/how-to-make-crystals/ Source: http://laughingkidslearn.com/how-to-make-crystals/
  9. 9. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Diarrhea • Diarrhea is the overflow of fluid • When intestine cannot properly handle the excess of fluid, diarrhea ensues
  10. 10. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Washing Machine Analogy What if we imagine the intestine as a washing machine? Source: http://www.lg.com/us/washers/
  11. 11. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Analogy Draining pipe = LYMPHATICS Washer connections ARTERY VEIN Drum Drum = The intestine Artery and vein supply fluids for secretion
  12. 12. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Analogy continued Incoming fluids: what we eat and what is further supplemented by the digestive tract, i.e. water, food and secretions from various glands Laundry, water and detergents Spun laundry Solid waste
  13. 13. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 What is most important to control the flow? • Lets the water through • Controls the flow from washer in to drainage • Critical element for proper fluid management INTESTINE Holes = absorptive channels Absorbs fluids into the body ABSORPTION
  14. 14. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 What if there were no channels? Pot, no channelsDrum, with channels
  15. 15. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 No channels = overflow 2. Massive overflow 3. Fluids are not “absorbed”1. Machine fills in quickly = DIARRHEA Source: https://www.rotorooter.comSource: http://newsroom.electrolux.com/uk/
  16. 16. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Channels in the intestine Intestine Ion channels • Very complex proteins • Can absorb OR secrete • Absorptive channels = mature enterocytes
  17. 17. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Importance of Absorption
  18. 18. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Basic intestinal organization Source: http://medicienterprises.com/2015/06/27/show-214/
  19. 19. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Normal Intestine • Mature cells absorb • Immature cells secrete • Absorption dominates secretion • Mature cells cover villi and immature cells cover glands IEC = Intestinal Epithelial Cell Mature IEC Immature IEC
  20. 20. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 A concept of maturation • Intestinal cells are born in the glands and then move up the villus • They normally die at the tip of the villus • As they move up the villus, they mature and change function from secretion to absorption • This process takes 3-5 days Mature IEC Immature IEC
  21. 21. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Mature IEC Immature IEC Single cell movement from the bottom of the crypt to villus tip. Lifecycle of enterocytes
  22. 22. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Absorption > Secretion Efficient absorption Continuous secretion: 2 gallons at the end of small intestine Absorption keeps fluid balance in check
  23. 23. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 It’s all caused by Myo5b deficiency • In MVID, the intestinal cell never understands that it has entered the phase when it must begin feeding the body via absorption. • Ion channels don’t appear because MVID intestine is “not aware” that it has to insert ion channels (strainers) into its surface. • Instead, it is permanently frozen in the immature state where its main task is to secrete fluids into the intestinal opening.
  24. 24. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 MVID Secretion > Absorption Absent absorption Continuous secretion: 2 gallons at the end of small intestine Nothing checks it: massive overflow
  25. 25. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Medical prognosis • This stage is typically called intestinal failure. • Total Parenteral Nutrition (TPN) and bowel transplantation are the only options currently available to patients.
  26. 26. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Current treatment options Patients are sustained on TPN (with various modifications, i.e. Omegaven) Racecadotril Somatostatin/Octreotide Antibiotics Tacrolimus Prednisolone Dopamine Cholestyramine Loperamide Lactulose Mannitol Cyclophosphamide Bowel transplant Only 1 option: Daclizumab L-tyroxine Ranitidine Codeine Urogastrone Pentagastrin Metronidazole ACTH Cromoglycate disodium Zinc EGF-1 Pedialyte Attempted treatments:
  27. 27. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Problem Treatment must address all aspects of the MVID pathogenesis.
  28. 28. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Alternative Treatment in Development Shylicine™
  29. 29. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Effect of Shylicine™ Epithelial cell have all the necessary tools to restore absorption. These tools are proteins encoded in the genes. + = Ion channels reconnect the opening of the intestine and the body, restoring absorption.
  30. 30. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Effect of Shylicine™ "Teaches" intestine how to make and properly insert absorptive ion channels. Shuts down additional secretion of fluid, preventing “overfill”.
  31. 31. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 How does it "teach"cells? By-passes the inability to mature induced by the absent Myo5b Activates alternative genes Only knows how to secrete DIY weekend warrior Mature IEC Immature IEC
  32. 32. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Effect of Shylicine™ Shylicine TM Mature IEC Immature IEC
  33. 33. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Shylicine™ affects all levels of intestinal organization. Source: http://medicienterprises.com/2015/06/27/show-214/ Designed to restore intestinal morphology
  34. 34. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Normal-looking cells can be found throughout MVA epithelium(arrows) Why do we think it’s possible From Kravtsov et al., 2016
  35. 35. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Where we are today: Targeting EU - Formulated the drug. - Patented the formula. - Submitted Orphan Drug Designation (ODD) application with European Medicines Agency (EMA). - Setting up for clinical trials. - Developing a rapid diagnostic test for MVID.
  36. 36. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 How can you help? - Stool samples for diagnostics. - Patients and investigators for clinical trials. Research and development Education - We want to understand what is it like living with MVID. - Collaboration in raising awareness of MVID. - Feedback on our educational materials. - MVID educational website development.
  37. 37. This is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc. 9.3.17 Thank You! This presentation is an educational resource, courtesy of Vanessa Research, Inc. © 2017 Shylicine™ is a registered trademark of Vanessa Research, Inc.

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