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A Universal Genetic Switch for Increasing Plant Yields, Stress Tolerance and Product Shelf Life
- 1. ©2017 | www.agribodytech.com 1 A Universal Genetic Switch for Increasing Plant Yields, Stress Tolerance and Product Shelf Life Jerry Feitelson, Ph.D., Co-Founder & CEO | jerry@agribodytech.com | (858) 349-3603
- 2. ©2017 | www.agribodytech.com 2©2017 | www.agribodytech.com THE PROBLEM • YIELD: Highest value trait to farmers Conventional breeding reaching yield limits • Tens of $Billions in crop loss caused by: Post-harvest senescence Disease (bacterial and fungal pathogens) Stress (drought, low nutrients, salt, cold, heat)
- 3. ©2017 | www.agribodytech.com 3©2017 | www.agribodytech.com THE BIG IDEA Avoids GMO controversies • For innovative seed companies • Dissatisfied with yield improvement • Patented technology uses genome editing for >20% yield increase & ↑ StressT • Small non-regulated deletions in a gene determining cell fate • Technology proven in field trials
- 4. ©2017 | www.agribodytech.com 4 Hypusine eIF-5A DHS Genetically Modifying a Biological Switch Promotes Plant Growth −Lysine eIF-5A Cell Growth/ Division Cell Apoptosis • Increased biomass and seed yield • Enhanced tolerance to stress & disease • Extended shelf life of perishable products + Results of gene switch
- 5. ©2017 | www.agribodytech.com 5 Value Proposition 1. Enhanced Shelf Life (↓ eIF-5A1 senescence) 2. Enhanced Disease Tolerance (↓ eIF-5A2 pathogen) 3. Enhanced Seed Yield / Biomass (↑ eIF-5A3 growth) Each eIF-5A isoform is hypusinated ↓ DHS : Positively effects all 3 traits
- 6. ©2017 | www.agribodytech.com 6 1a. Enhanced Shelf Life (↓ eIF-5A1 / ↓ DHS) Agribody Control At harvest 7 days 14 days Control Agribody Days 14 21 280 44 Delayed fruit softening & spoilage 2 - 3X longer shelf life
- 7. ©2017 | www.agribodytech.com 7 Control Agribody Control AgribodyControl Agribody Control Agribody 7 daysAt harvest 14 days 21 days 1b. Enhanced Shelf Life (↓ DHS) Delayed leaf & flower senescence 3X longer shelf life
- 8. ©2017 | www.agribodytech.com 8 Tolerance to fungal / bacterial disease 2. Enhanced Disease Tolerance (↓ eIF-5A2 / ↓ DHS) Control (Sigatoka-infected) Banana Pseudomonas syringae infection Tomato AgribodyControl Agribody (Sigatoka-reduced)
- 9. ©2017 | www.agribodytech.com 9 * P < 0.01 50.71 128.39 195.2 77.38 0.00 50.00 100.00 150.00 200.00 250.00 Vector Only Line 4 Line 3 Line 2 SeedWeight/Plant(mg) Seed-yield of poplar eIF5A3 transgenic Arabidopsis * * * ~150% ~300% ~50% 3a. Enhanced Seed Yield in Arabidopsis (↑ Poplar eIF-5A3)
- 10. ©2017 | www.agribodytech.com 10 T2-Line 3 at 6 weeks Control T2-Line 3 at 3 weeks Control 3b. Enhanced Biomass in Arabidopsis (↑ Poplar eIF-5A3)
- 11. ©2017 | www.agribodytech.com 11 • 50–300% increased vegetative & reproductive mass • Enlarged root structure • Enhanced stress tolerance − drought, nutrient, salt, heat, cold 3c. Enhanced Biomass in Canola (↓ DHS) Control Agribody Control Agribody Ref: Ma et al. (2005) Physiol. Plant. 124:493-503
- 12. ©2017 | www.agribodytech.com 12 0 50 100 150 200 250 300 350 WT TG1 TG2 TG3 TriacylglycerolFA(µgmg -1 seeds) 0 10 20 30 40 50 60 70 16:0 18:0 18:1 18:2 18:3 Fatty Acid FattyAcid%ofTotal 3d. No Change in Canola Seed Oil nor FA composition (↓ DHS)
- 13. ©2017 | www.agribodytech.com 13 Phloem Mature region of the Root PAteIF5A3::GFP-AteIF5A3 fusion Root Localization of eIF-5A3 expression: Phloem 6 days growth Ref: Ma et al. (2010) Plant Cell & Environ. 33:1682-96 Laser scanning confocal microscopy Root Mature Zone-2
- 14. ©2017 | www.agribodytech.com 14 p s f f x p s s f f x p eIF-5A3: Localized in companion cells Inflorescence stem base sections of 5-week-old plants p: phloem cells x: xylem vessels s: sclerenchyma f: phloem fibers : sieve tube elements 50 m 50 m 20 m PAteIF5A3::GFP-AteIF5A3 fusion
- 15. ©2017 | www.agribodytech.com 15 Hypotheses • Regulates expression of proteins involved in translocation of photosynthate into the phloem • May function as a transcription factor for a plasma membrane ATPase localized in companion cells Tissue & Cellular Localization of Growth eIF-5A3
- 16. ©2017 | www.agribodytech.com 16 Transgenic Alfalfa Field Trial
- 17. ©2017 | www.agribodytech.com 17 CONTROL AGRIBODY • 3rd most valuable crop • >$8B hay market in U.S. • Alfalfa breeding challenge is improvement of both forage yield and quality − Often inversely correlated − Low yearly gains: <0.2 – 0.3% • Elite varieties of alfalfa developed that constitutively overexpressed eIF-5A3 − Over 2 years of field trials averaged 20 – 45% higher yields − Maintained high forage quality − Manuscript submitted FIELD TRIAL SUCCESS: ALFALFA
- 18. ©2017 | www.agribodytech.com 18 Higher yields do not result in significantly lower quality Field Trial Success – Alfalfa CP: Crude Protein ADF: Acid Detergent Fiber NDF: Neutral Detergent Fiber RFQ: Relative Forage Quality 2010 Field trial established Salem, WI 2011-2012 Agronomic evaluation, forage yield & quality measured 22 alfalfa clones 2012-2013 Confirmed data 22 alfalfa clones Three lines significant at 95%; others at 90% eIF-5A3 Alfalfa Hay Category CP ADF NDF RFQ Supreme >22 <27 <34 >185 Hay Yield Premium 20-22 27-29 34-36 170-185 DW (g) % Control Good 18-20 29-32 36-40 150-170 2011 008-PIP-036 199.8 136% 21.5 28.7 34.2 200.6 008-PIP-029 186.6 127% 22.2 28.4 33.8 201.1 009-PIP-076 183.7 125% 22.3 28.2 33.6 202.9 Control 146.5 100% 22.0 27.0 32.1 216.3 2012 009-PIP-010 144.8 133% 18.9 30.4 36.3 172.9 008-PIP-046 132.0 122% 18.8 30.5 36.4 170.9 008-PIP-008 124.2 114% 19.0 31.0 36.9 170.6 Control 108.6 100% 18.8 30.0 35.9 176.7
- 19. ©2017 | www.agribodytech.com 19©2017 | www.agribodytech.com Risk Reduction in Genome Edited Alfalfa First Genome-Edited Alfalfa Plant Designated as Non-Regulated by USDA-APHIS Oct. 2, 2017 Calyxt Products Confirmed Non-Regulated Using TALEN® • Improved quality alfalfa 50 other Letters of Inquiry reviewed by APHIS • Reduced browning potato • Cold storable potato • Powdery mildew resistant wheat • High oleic / low linolenic soybean • High oleic soybean
- 20. ©2017 | www.agribodytech.com 2020 • Broad Coverage − 16 issued US Patents + 5 published US Patent Applications − Foreign counterparts in several countries − New applications for genome editing of DHS − CRISPR 3.0 in-license from Benson Hill Biosystems • Matter & Methods claims: important traits − eIF-5A overexpression • Higher seed & biomass yields • Tolerance to abiotic stresses − DHS knock-downs • Delayed senescence • Larger leaves • Higher seed yields • Stress tolerance Strong IP Portfolio
- 21. ©2017 | www.agribodytech.com 2121 ATI Executive Team Paul Kreutz Corporate Counsel • Represented many VC firms • Counsels & helps structure growth-oriented entrepreneurial enterprises • B.A. (Yale), LL.B. (Stanford) Jerry Feitelson, Ph.D. CEO / Co-Founder • >30 years R&D, IP, Licensing & Bus Dev experience • Managed $10Mil royalties; Negotiated $7Mil license • Patented B.t. genes/proteins lead to $850Mil valuation • B.S. (MIT), Ph.D. (Stanford) John Thompson, Ph.D. Chief Scientist / Co-Founder • U. of Waterloo (Professor Emeritus, Associate VP) • Invented eIF-5A/DHS technology • B.S. (Toronto), Ph.D. (Alberta), Fellow of Royal Society of Canada Jim Goode Acting CFO • 35 years managing financial/ admin functions of high-tech, biotech and start-ups • Raised >$100Mil • MBA (UCLA), CPA (Arthur Young)
- 22. ©2017 | www.agribodytech.com 2222 ATI Consultants / Advisors Alan Bennett, Ph.D. Chair, SAB • UC-Davis (Distinguished Professor of Plant Science) • Transformed/characterized elite alfalfa with eIF-5A • Runs advanced genetics lab • B.S. (UC-Davis), Ph.D. (Cornell) Jerry Caulder, Ph.D. Advisor • Known as the “Father of Agricultural Biotechnology” • 15 years with Monsanto; as CEO, built $1.2Bil valuation • Lead 2 other companies, Chair of Athenix, sold for $400Mil. Founded Finistere Ventures • B.S. (SE Missouri State U.), Ph.D. (U. Missouri) Vaughn Smider, M.D., Ph.D. Advisor • CSO of Sevion Therapeutics, Founder/President of precursor company, Fabrus. • Associate Professor at The Scripps Research Institute • Leadership Council for American Cancer Society • B.A (Hiram College), M.D. & Ph.D. (Stanford U.) Craig Williams Field Trials / Regulatory • 25 years experience managing seed companies • Knowledgeable in seed business operations, regulatory affairs, field trials, M&A due diligence • B.S. (Bradley U.)
- 23. ©2017 | www.agribodytech.com 23©2017 | www.agribodytech.com Potatoes Technology attractive to major players BananasCorn & Soy Alfalfa CRISPR 3.0 Coffee Peanuts
- 24. ©2017 | www.agribodytech.com 2424 Summary Join ATI in building value by licensing or co-developing ultra- high yield, stress- resistant crops • Proven Technology - Broad IP, Field Trials • Experienced Team - Ag biotech serial entrepreneurs, resourceful, ethical • Great Traction - Successful Seed Round fund-raising - Started alfalfa co-development - Revenues: potato & coffee licenses - In-licensed CRISPR 3.0
- 25. ©2017 | www.agribodytech.com 25 THANK YOU! Jerry Feitelson, Ph.D., Co-Founder & CEO jerry@agribodytech.com | (858) 349-3603 | www.agribodytech.com