Plant-made Pharmaceuticals Industrials: Expectations Realities Scott Deeter Ventria Bioscience June 17, 2003

1. Plant-made Pharmaceuticals & Industrials:Expectations & Realities Scott Deeter Ventria Bioscience June 17, 2003

2. 8/22/2012 2 What are PMPs and PMIPs? Plant-made Pharmaceuticals (PMPs) New category of products Plant is the host for the manufacture of the active ingredient for a drug. Following harvest, plant material is processed to recover and purify the active ingredient. Active ingredient manufacture and marketing is regulated by FDA Plant-made Industrial Products (PMIPs) New category of products Plant is the host for the manufacture of an industrial product, such as an industrial enzyme. Following harvest, plant material is processed to recover and purify the industrial compound.

3. 8/22/2012 3 Core to our technology platform is transformation and expression. Ventria stably inserts��.. Plasmid DNA containing gene of interest stably inserted into plant genome, with the transformed callus developing into the whole plant. Core to our technology platform is transformation and expression. Ventria stably inserts��.. Plasmid DNA containing gene of interest stably inserted into plant genome, with the transformed callus developing into the whole plant.

4. 8/22/2012 4 Why Plant-made Pharmaceuticals? Plants can produce complex biologics:Plants such as rice and barley are able to produce complex biologics such as monoclonal antibodies and complex proteins. Plants are highly scalable:Rice and barley can scale up capacity at the rate of 2,500 times annually. Plants are economically superior:Production economics are very attractive, especially for oral and topical biologicals. Capital cost is a fraction (10%) of the traditional systems of production.

5. 8/22/2012 5 Why Food Crops? Grains such as rice and barley are free of infectious contaminants from human or animal origin such as viral (west nile virus) and prion (BSE) contamination. In addition, grains do not have toxic contaminants that are difficult to remove (ie. phenolics). These crops provide a host that is generally recognized as safe (�GRAS�) and well characterized. Rice and barley can store the target biopharmaceutical for more than 2 years, reducing the need to over-produce or maintain idle capacity. The seed and target gene are stable and replicable across multiple generations, providing consistent quality, a critical requirement of FDA. Using the plants biological process for storing proteins achieves much better economics as a result of the high yields and ability to maintain quality of raw material inventory.

6. 8/22/2012 6 Why Self-Pollinating Crops? Male and female reproductive system contained within the same plant, providing self-fertilization. Several studies have shown that beyond 30 feet, no outcrossing has been detected. Rice Biosafety: World Bank Technical Paper, Clegg et al. 1993. Result of a 40-member consultation supported by the USDA/APHIS, the World Bank, IRRI and the Rockefeller Foundation. This study summarized several studies showing no outcrossing beyond 30 feet. UC-Davis: Biggs experiment station. 4 replications, with 15 foot Liberty-Link transgenic center circle surrounded by 48 foot radius non-transgenic. Beyond 6 feet, no outcrossing was detected. Between 0 ft and 6 ft from the donor, the outcrossing rate was 0.00001% (16 seeds out of 1,680,000 tested). Ventria utilizes a minimum setback distance of 100 feet.

7. 8/22/2012 7 Environmental Stewardship Grown under permit issued by USDA. Ventria directly manages production using standard operating procedures (�SOPs�) with trained field personnel, maintaining ownership of seed and grain. (HACCP). Rice and barley are processed before any product is sold.  100% internal audit of our SOPs and regulatory requirements. Dedicated field production equipment that comes into contact with plant material. Dedicated harvesting, storage and processing infrastructure. Double-contained transportation. Ventria�s production practices are audited by CCIA and inspected by USDA/APHIS. (Multiple inspections in 2003)

8. 8/22/2012 8 Expectations Plant-made Pharmaceuticals: Today: ~ 100 acres; 18 companies 2008: ~ 10,000 acres; 6 companies Plant-made Industrial Products: Today: ~ 500 acres; 8 companies 2008: ~ 100,000 acres; 6 companies

9. 8/22/2012 9 Selected PMPs in Development Company Targets Host Biolex Multiple Lemna Dow Multiple Corn EpiCyte Herpes Corn Large Scale Biology Surgical Blood Loss Tobacco (Viral) Fabry�s Disease??? Meristem Cystic Fibrosis Corn Monsanto Cancer Corn SemBioSys Cosmetics Canola Safflower Ventria Infectious Disease Rice Gastrointestinal Disease

10. 8/22/2012 10 Global Health Problems The science behind this product is clear and the performance data is definitive.The science behind this product is clear and the performance data is definitive.

11. 8/22/2012 11 In addition to the feed efficiency data, gut histology data supports that this product performs similarly to antibiotics. As you can see, on average lamina propia thickness as well as leukocyte populations are lower than that of chicks fed diets without feed antibiotics. Lactahedrin is antiviral.In addition to the feed efficiency data, gut histology data supports that this product performs similarly to antibiotics. As you can see, on average lamina propia thickness as well as leukocyte populations are lower than that of chicks fed diets without feed antibiotics. Lactahedrin is antiviral.

12. 8/22/2012 12 In addition to the feed efficiency data, gut histology data supports that this product performs similarly to antibiotics. As you can see, on average lamina propia thickness as well as leukocyte populations are lower than that of chicks fed diets without feed antibiotics. Lactahedrin is antiviral.In addition to the feed efficiency data, gut histology data supports that this product performs similarly to antibiotics. As you can see, on average lamina propia thickness as well as leukocyte populations are lower than that of chicks fed diets without feed antibiotics. Lactahedrin is antiviral.

13. 8/22/2012 13 Realities �.the Benefits will take time to deliver Many products in the pipeline New Product Development: 5+ years First PMPs: 2006 Many products by 2008