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Modern Meadow Reveals the Technologies behind its Biofabricated Leather Materials

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Modern Meadow CTO Dave Williamson presents at Society for Industrial Microbiology and Biotechnology, revealing the shift from tissue engineering to fermentation, demonstrating Modern Meadow’s ability to produce collagen at commercial scale. The development of a biofabricated leather material production process through the synergy of high yielding collagen production process and a bottom-up recapitulation of leather

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  • Skins and hides are by-products of meat industry therefore leather processing is crucial to protect the environment and for sustainability. If these skins and hides are NOT processed, they would end up in landfills resulting in significant environmental impacts. I think in order to solve the problem, we should start with the top of the food chain making meat in the lab then we will not worry about skins and hides by-products. MORE IMPORTANTLY IS THAT LIVESTOCKS ARE FARMED FOR MEAT AND NOT AS A SOURCE OF LEATHER SO IT IS UNFAIR TO SAY LEATHER PRODUCTION RESULTS IN FARMING MORE LIVESTOCKS. I do NOT believe this technology will last for 10-20 years. Regarding the science part, Good works! This is nice presentation for a 101 collagen chemistry paper? I believe you need some sort of artificial crosslinks to make the fibrils which are not mentioned in the slides! Where are the natural collagen crosslinks? Where are the enzymes that add hydroxy group to lysine to make hydroxylysine which is crucial for making the natural crosslinks? where are the enzymes that activate the lysine and hydroxylysine residues to form allysines the intermediates for the formation of collagen crosslinks? I’m disappointed as these questions have not been addressed in the slides and collagen molecules assembly into fibrils has not been addressed as well. I hope to address these questions in your next slide. Thank you.
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  • Fascinating work but the environmental argument is spurious as livestock are not, and have never been, reared for the leather industry. Hides and skins are a by-product of the meat industry and the stated environmental concerns, which are also questionable, will not be addressed by an alternative collagen source for the leather industry but by reducing meat consumption or providing a viable alternative to current meat sources.
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Modern Meadow Reveals the Technologies behind its Biofabricated Leather Materials

  1. 1. 7/30/2017 1 D avid Williamson Chief Technology Officer The development of a biofabricated leather material production process through the synergy of high yielding collagen production process and bottom-up material design.
  2. 2. 7/30/2017 2 Andras Forgacs CEO Co-founder, Organovo (NYSE: ONVO) Venture investor, repeat entrepreneur, corporate innovator Susan Schofer VP Product 12+ years experience in industrial biotech R&D and commercialization David Williamson CTO Former Chief of Staff to DuPont CSTO Proven industrial biotech strategy, R&D and manufacturing technology leader Suzanne Lee Chief Creative Officer Fashion designer & biodesign pioneer Founded Biocouture and the Biofabricate summit. Author: Fashioning the Future Rex Liu VP Finance Former VP Controller at Tesla Motors 15+ years of finance & accounting in high growth tech & manufacturing Luck Dookchitra Head of People Proven people & talent leader 10+ years experience in scaling global startups iPEC-trained executive coach Our Executive Team
  3. 3. 7/30/2017 3 CAPITAL RAISED From top-tier investors and grants $55M PATENTS FILED 77 Novel, scalable approaches to producing materials (process and product) SQUARE FEET 60,000 World-class biotech R&D labs FULL-TIME PROFESSIONALS 70 Brooklyn, NY New York Location 16 PhDs Tissue engineering Cell engineering Biochemistry Chemical engineering Bioengineering Biophysics Chemistry Material science Polymer science Leather chemistry Design and business Modern Meadow by the Numbers
  4. 4. 7/30/2017 4 LIVESTOCK IS A PROBLEM 60 billion animals farmed annually is pushing resource limits GROWING FOOTPRINT Livestock is largest user of land, water and contributor to climate change. Footprint expected to double by 2050. RISING PRICES Animal products are massive markets with dramatically rising prices 38% 20152009 +300% HIDE PRICES US Hide Prices O u r D e p e n d e n c e o n An i m a l P r o d u c t s i s Pushing Planetary Limits ICE-FREE LAND ?? GLOBAL WATER GREENHOUSE GASSES 8% >14% ?? ?? 2050TODAY 7 Billion People 60 Billion Land Animals 10 Billion People 100 Billion Land Animals
  5. 5. 7/30/2017 5 FACTORY FARMING TRADITIONAL PROCESS Minimal environmental impact Continuous roll manufacturing Uniform material production High innovation potential Poor defect control Limited innovation potential Large environmental impact Low cutting efficiencies ANIMAL HIDE TANNING LEATHER HIDE MODERN MEADOW PROCESS BIOFABRICATED LEATHER MATERIALS CELL ENGINEERING BIOPROCESSING BIOFABRICATION A New Way to Create Materials
  6. 6. 7/30/2017 6 “A general term for hide or skin with its original fibrous structure more or less intact, tanned to be imputrescible…” – BS 2780 Processed to remove any non- collagenous material (flesh, fat, and hair). Comprised of mostly collagen proteins organized into three distinct layers. Requires Tanning/Retanning to stabilize the collagen protein structure and create a supple material that is both comfortable and tough. What is Leather?
  7. 7. 7/30/2017 7 Most abundant protein in mammals (25-35%) • 28 different mammalian collagen types • Fibrillar collagen: Type I, II, III, V, XI • Skin = Type I & III GLY-PRO-PRO MODEL Glycine-X-Y • X often proline • Y often hydroxyproline • Glycines form center of triple helix Pro = Orange Gly = White Collagen Family
  8. 8. 7/30/2017 8 1 PPI (peptidylproline cis-trans isomerase) converts prolines to trans form 2 2P4HA + 2P4HB assemble into tetramer 3 P4HAB + Ascorbic Acid + Iron +2-oxoglutarate converts proline  hydroxyproline P o s t - Tr a n s l a t i o n a l M o d i f i c a t i o n s : Prolyl Hydroxylation and Assembly of the Triple Helix RER Translation ER and Golgi modification Intracellular Procollagen
  9. 9. 7/30/2017 9 • α2β2 tetramer (240 kD) composed of two interlocking “V” shaped heterodimers [SEM] • α subunit (64 kD) is catalytically active site • Β subunit (60 kD) is structural • Complex reaction that requires ascorbic acid, 2-oxoglutarate, Oxygen, and proline P4HA and P4HB Structure and Function
  10. 10. 7/30/2017 10 HOST TITER PROLINE HYDROXYLATION CULTURE CONDITION COST Mammalian cell culture (293T, CHO) Very low (15-30 mg/L) Fully hydroxylated Mammalian cell culture media High Plant (Collplant™) Low (50–100 μg/100 g leaf material) Under hydroxylated Live plant Medium Yeast (Fibrogen™) Medium (up to 1.5 g/l) Fully hydroxylated Methanol containing yeast media Low Prior Work on Recombinant Collagen
  11. 11. 7/30/2017 11 COLLAGEN MOLECULAR STRUCTURE 1466 AA Strains selected and engineered for elevated collagen production and hydroxylation activity CHROMOSOMAL INTEGRATION into Pichia pastoris Promoters for Collagen, P4HA and P4HB tailored for both activity and development of desired triple helical structure Signal peptides selected and engineered for optimum hydroxylation activity N-pro-peptide Telo Telo C-pro-peptideHelix Expression Vector Design
  12. 12. 7/30/2017 12 P4HA activity verified via tetramer assay and shown to be significantly higher(2-3X) than CHO Cell Controls* • Km ~ 22µM 185 115 80 65 50 30 270 205 150 85 65 120 85 65 120 *Kivirikko et al. The FASEB Journal 1989 Control 24 Well Co-expression of Collagen, P4HA and P4HB Collagen P4HA P4HB
  13. 13. 7/30/2017 13 35Time (hrs.) 58 80 96 Productivity remains constant throughout the fermentation process Performance at a 1000L scale matched well with predicted performance Biomass(gWCM/L) 500 400 300 200 100 0 1.0 0.8 0.6 0.4 0.2 0.0 0 20 40 60 80 100 Collagen(%ofFinal) Fermentation time (h) Demonstration of Scale-able Fermentation Process
  14. 14. 7/30/2017 14 MODERN MEADOW COL3CONTROL DSC Analysis demonstrated in a Tm of >38°C Hydroxyproline content demonstrated to be ~38-44% of total AA (~80-90% of expected sites) SEC-MALLS Characterization of Post -DSP Col3
  15. 15. 7/30/2017 15 MODERN MEADOW BOVINE CONTROL Fibrillation process developed to create highly ordered fibril structures • D-band spacing was determined to 67nm • Resolution of D-banding result of minimizing defects created during self-assembly • Fibril widths of 250-300nm • Fibril lengths in excess of 50microns Bovine Collagen vs Modern Meadow Collagen
  16. 16. 7/30/2017 16 Collagen Monomer Large Fibril MODERN MEADOW LEATHER 3 4 Assembly Assembly Transformation of Collagen Monomers to a Biofabricated Material
  17. 17. 7/30/2017 17 MODERN MEADOW RAW HIDE MODERN MEADOW HIDE SEMI-FINISHED DYED Modern Meadow Biofabricated Leather Material
  18. 18. 7/30/2017 18 Bovine- Control STRESS(MPA) Structure A Structure B Structure C STRAIN (%) Tensile Analysis of Modern Meadow Biofabricated Leather
  19. 19. 7/30/2017 19 Demonstrated the ability to express high quality Collagen Type-3 protein via fermentation. Conclusions Developed a Collagen production strain designed to operate in existing fermentation facilities with minimal capital investment shown to scale to 1000L. Developed route to high performing Biofabricated leather materials starting with Collagen monomers. 1 2 3
  20. 20. 7/30/2017 20 T H A N K Y O U ACKNOWLEDGMENTS: Lixin Dai, Julia Borden, Brenden Purcell and Hemanthram Varadaraju, Jason Polzin and the rest of the Modern Meadow Team Modern Meadow, NY, NY, USA

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