Presentation of Dr Scott Deeter President and Chief Executive Officer Ventria Bioscience Plant made Pharmaceutical and Industrial Products Expectations and Realities

Plant-made Pharmaceuticals & Industrials: Expectations & Realities Scott Deeter Ventria Bioscience June 17, 2003 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. 8/22/2008 2 ExpressTec™ 8/22/2008 3 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. 8/22/2008 4 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. 8/22/2008 5 Why Self-Pollinating Crops? • Male and female reproductive system contained within the same plant, providing selffertilization. • 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. 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). – UC-Davis: Biggs experiment station. 4 replications, with 15 foot Liberty- • Ventria utilizes a minimum setback distance of 100 feet. 8/22/2008 6 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) 8/22/2008 7 Expectations • Plant-made Pharmaceuticals: – Today: – 2008: ~ 100 acres; 18 companies ~ 10,000 acres; 6 companies • Plant-made Industrial Products: – Today: – 2008: ~ 500 acres; 8 companies ~ 100,000 acres; 6 companies 8/22/2008 8 Selected PMPs in Development Company Biolex Targets Multiple Host Lemna Dow EpiCyte Large Scale Biology Multiple Herpes Surgical Blood Loss Fabry’s Disease??? Cystic Fibrosis Cancer Cosmetics Infectious Disease Gastrointestinal Disease Corn Corn Tobacco (Viral) Meristem Monsanto SemBioSys Ventria Corn Corn Canola Safflower Rice 8/22/2008 9 Global Health Problems Leading Infectious Killers of Childern Under 5 (Millions of worldwide deaths) 2.5 2 1.5 1 0.5 0 Ventria’s Focus Acute Respiratory Infections Diarrheal Diseases AIDS Measles Source: World Health Organization 8/22/2008 10 Malaria TB Global Health Problems Why solutions to these problems have not been developed? Problem   Inability to produce therapeutic solutions in sufficient quantities High cost of products produced in traditional systems 8/22/2008 11 Global Health Problems Ventria’s Solution  Orally delivered Lactoferrin and Lysozyme produced using ExpressTec™, plant-made pharmaceutical production system  Able to produce 1,000’s of kilograms with minimal capital investment  Biologic yield is very high, and the processing is efficient, reducing the cost of production. 8/22/2008 12 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 8/22/2008 13