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Food security and crops productivity

Food security and crops productivity. Growing wealth Food quality and change in diet. Climate change. Growing world population. Limited resources: land, water, and energy. Corn Yield Components to 2030. CORN YIELD POTENTIAL TO 2030 IN THE UNITED STATES.

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Food security and crops productivity

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  1. Food security and crops productivity Growing wealth Food quality and change in diet Climate change Growing world population Limited resources: land, water, and energy

  2. Corn Yield Components to 2030 CORN YIELD POTENTIAL TO 2030 IN THE UNITED STATES Additional gains from breeding, ag practice improvements and new biotechnology products bring yield potential to ~300 bu/ac by 2030 (185 t/ha)

  3. Soybean Yield Components to 2030 SOYBEAN YIELD POTENTIAL TO 2030 IN THE UNITED STATES Additional gains from breeding, ag practice improvements and new biotechnology products bring yield potential to 80 bu/ac by 2030

  4. MONSANTO’S VITAL STATISTICS A leader in seeds, crop protection and biotechnology Headquartered in St. Louis Employs more than 20,000 people worldwide More than 500 locations worldwide in 4 primary regions — Europe/Africa, Asia Pacific, Latin America and North America Corn Soybean LA Vegetable & Fruit E-A A-P All other Crops NA Monsanto Company at a Glance Monsanto is 100% focused on agriculture A LEADER IN THE FIELD OF AGRICULTURAL TECHNOLOGY Sales by Seeds and Traits Cotton Sales by Geography Dedicated to Bringing the Next Generation of Ag Products to the Market

  5. DISCOVERY PHASE I PHASE II PHASE III PHASE IV BREEDING GENOMICS MARKERS ELITE GERMPLASM IT PLATFORM ANALYTICS COMMERCIAL BIOTECHNOLOGY Monsanto R&D Pipeline Structure BREEDING and BIOTECHNOLOGY form two parallel R&D pathways to commercial products that are linked by shared tools and technology. • Monsanto’s corn germplasm library is assembled from 36 breeding programs in 12 different countries

  6. Discovery Gene/Trait Identification Ag Biotech Driven by Lengthy Product Development Cycle and Large Investment* On Average: Time to market: 8-10 years Total expense: ~$100M $20-40M (90%) $15-30M (75%) • Regulatory submission • Seed bulk-up • Pre-marketing $10-15M (50%) • Trait integration • Field testing • Regulatory data generation Spending (Probability of Success in %) • Trait development • Pre-regulatory data • Large scale transformation $5-10M (25%) $2-5M (5%) • Gene optimization • Crop transformation • High throughput screening • Model crop testing 4 6 8 9 10 5 3 7 Year 0 2 1 PhaseIII Phase I Phase II Phase IV Proof of Concept Early Development Advanced Development Regulatory Submission * Numbers (time duration, spending, and probability of success) are all estimates. The actual for individual projects could vary.

  7. TRAIT INTEGRATION FIELD TESTING MONSANTO DISCOVERY + COLLABORATIVE PARTNERS REGULATORY DATA GENERATION REGULATORY SUBMISSION KEY INFLECTON POINT:AFTER PHASE II COMMERCIAL SUCCESS GOES TO >50% WITH LEADS ON COMMERCIAL TRACK SEED BULK UP • Time estimates are based on our experience; they can overlap. Total development time for any particular product may be shorter or longer than the time estimated here. • This is the estimated average probability that the traits will ultimately become commercial products, based on our experience. These probabilities may change over time.

  8. Datasets are Derived from Many Sources and are Getting Exponentially More Complex Plant Physiology: Precise Trait Description Imaging RNA Profiles Genome Sequence Metabolite Profiles Field Performance Protein Profiles Protein Interactions

  9. Plant Transformation Remains a Key Enabling Technology: - A Blend of Molecular Biology, Cell Biology, and Automation- Elite Germplasm is a Key Automated explant excision and collection Optimized selection conditions Enhanced Agrobacterium strains, vectors

  10. Technology Advancements in Soybean Transformation Enables Gene Discovery and Product Development Event to Soil / FTE $ / Event to Soil Particle Gun-Gly Agrobacterium bulk inoculation Particle Gun-GUS Automated Explant Excision 1999 =Transition year for Agro-mediated process 2004 =Transition year for Automated Excision

  11. Linking Genotype to Phenotype is Critical: Automated Phenotyping and Field Trials Assembly – Line Automation Plant Growth and Physiology Corn Soy Cotton • Automated Plant Handling • Anticipatory Environmental Controls • Same Seed is Tested in Field • Optimal, Drought and Low Nitrogen Testing Broad acre field trail (corn drought) Image Analysis • Daily Imaging and Growth Rate • 1000s of measurements Per Gene • Visible and Hyperspectral Imaging

  12. Advances in Stacking Technology Vector stacks • Agrobacterium-mediated transformation has been used to deliver at least 10 transgenes • All genes intact and express Accelerated Trait Introgression Breeding Stacks • Trait introgression of multiple loci requires high throughput marker analysis • Molecular marker platform • Capability to analyze tens of millions of samples • Seed chipping technology reduces field space, sampling needs Hawaii Conversion Center 4 Generations/Year Corn Seed Chipper High Throughput Sampling Commercial Products A combination of Vector Stacks and Breeding Stacks

  13. A History of Innovation and New Product Introductions Soybeans Corn Sorghum Corn We have introduced about one new product and/or technology each year in the United States since 1996. These products are aimed at delivering benefits to farmers. Monsanto Agricultural Traits & Products Overview 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Soybeans Soybeans Winter Canola

  14. New Biotechnologies and New Products • TF-based regulation of gene expression • Drought-tolerance • High Yield Soy • RNA-based gene regulation • Pest Control- Next-generation Corn Rootworm Control • Metabolic Engineering- Vistive III

  15. Over-Expression of Plant Nuclear Factor Y (NF-Y) B Provides Drought Tolerance in Maize NF-YB2 interacts with NF-YC & localized in corn nucleus • Gene identified using screen in Arabidopsis • NF-Y transcription factor subunit • complex binds CCAAT box • Drought tolerance observed in greenhouse and field • Reduced leaf rolling • Improved photosynthesis • Cooler leaves • More grain yield Nucleus NF-YB2 GFP …with NF-YC A C NF-YB over-expressed in corn produces a cooler plant C B 40 34 32oC With Trait Without Trait With Trait Without Trait CCAAT-Box Reduced Leaf Rolling Reduced Leaf Temperature COLLABORATION WITH

  16. Bbx32 increases Soy Seed Yield • Arabidopsis protein Bbx32 increases seed yield when over-expressed in soy • Bbx32 increases plant growth resulting in more nodes, more pods and more yield • Gene ontology analysis of regulated genes suggests Bbx32 regulates growth, clock and/or light perception processes Increased pod number in proof of concept Bbx32 transgenic soy 1 2 3 4 5 6 7 8 event 2 event 4 wildtype WT Event 4 Transgenic Event COLLABORATION WITH

  17. Vistive III, a New High Stability Soybean OilSuppression of 2 enzymes through RNAi (FATB & FAD2) and crossing with Vistive I (FAD3 suppressed breeding line) alters flux in fatty acid biosynthesis to give a low lin, low sat, high-oleic soybean oil Plastid KAS D9 FATA Plastid KAS D9 FATA 16:0-ACP 18:0-ACP 18:1-ACP 18:1-CoA 16:0-ACP 18:0-ACP 18:1-ACP 18:1-CoA FAD2 (D12) FAD3 (D15) FAD2 (D12) FAD3 (D15) 18:1 (Ole) 18:2 (LA) 18:3 (ALA) FATB 18:1 (Ole) 18:2 (LA) 18:3 (ALA) FATB TAG TAG 18:0-CoA 18:0 (Ste) 18:0-CoA 18:0 (Ste) 16:0-CoA 16:0 (Pa) 16:0-CoA ER 16:0 (Pa) Wild type Vistive III Soybean ER Oil Body FAD2 intron FAD2 intron FATB 5’-UTR FATB 5’-UTR Oil Body 7Sa’ 3’-UTR

  18. Pest control from RNAi Corn Rootworm Cell Plant Cell Ingestion (uptake) Dicer 21-24mers systemic spread 21-24mers cleavage & amplification RISC Dicer 5’cap AAAAA mRNA recognition RISC X transcription no cleavage transcription target gene transcription transgene allelic variant In collaboration with Devgen

  19. Field analysis shows differences in performance between RNAi and Bt events RNAi construct Western corn rootworm (WCR, Diabrotica virgifera virgifera) is a prominent agricultural pest in corn 2008 Field Data – RDR vs. Event/Stack YieldGard Rootworm YieldGard Rootworm X RNAi Root Damage Ratings Non-transgenic RNAi Non-transgenic V-ATPase RNAi events YieldGardRootworm B.t. protein Cry3Bb YieldGard Rootworm x V-ATPase RNAi

  20. Cry3Bb stacked with RNAi offers root protection and reduced adult emergence Dual MOA provides a high effective dose with significant reduction in beetle emergence RNAi B.t. protein x RNAi B.t. protein

  21. The universe of RNA-based regulation continues to expand miR171 decoy variations modulate phenotype miR171_3B miR171_2M WT • Arabidopsis Plants expressing miR171 decoys show up-regulation of multiple endogenous targets (e.g. SCL6-III) • Pleiotropic phenotypes are observed in leaf morphology and fertility • Specific structure of decoy (mismatch vs. bulge) alters degree of miR171 inactivation miR171_3B decoy miR171_2M decoy SCL6-III (At3G60630) Expression A B A B A A 15.5 Log2 Expression (AU) 15.0 14.5 2 WT 2 1 Event 1 14.0 171_3B 171_2M 13.5 13.0

  22. Productive Collaborations Are Crucial to Deliver Constant Innovation to the Farmer Arcadia Biosciences, Inc. 1995 Land O’Lakes / Forage Genetics International Athenix Corp. Devgen NV BASF China R&D Center (MON Site) X HuazhongAg. U. Evogene Ltd. X GrassRoots Biotechnology Hunan University-RLK Bangalore R&D Center (MON Site) Mendel Biotechnology, Inc. The Solae Company Yale University X Chromatin, Inc. Senesco Technologies, Inc. Protabit, LLC Campinas R&D Center (MON Site) Danforth Center

  23. Acknowledgments: • RNAi Research Projects • Claire CaJacob • Bob McCarroll • Ken Gruys • Ron Flannagan • Jim Baum • Toni Voelker • Isaac Banks • Elizabeht Wiggins • All Collaborators • Transformation / Stacking • Dave Somers • Larry Gilbertson • Genomics • Allen Christian • Rita Varagona • Wei Wu • Yield & Stress Traits • Tom Ruff • Janice Edwards • Mike Stephens • Marie Petracek • Trait Development • Mike Hall

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