The Dow Chemical Company Dowpharma and Dow AgroSciences

1
The Dow Chemical Company Dowpharma and Dow
AgroSciences

• Kerr Anderson
• and
• Kyle Lathrop
• Galveston, October 2005

2
Dow Chemicals Resources and Experience

• 30 years of pharmaceutical experience
• cGMP API and intermediate manufacture (g to mt)
  assets and experience
• Comprehensive analytical and process development
  capabilities
• Access to Dows global capabilities and
  technologies
• Experience of a global leader in chemical
  manufacturing
• 40 billion revenue
• RD investment gt1.0 billion

3
Alignment within Dow
Dow AgroSciences
Hydrocarbons Energy
? Other Dow operating segments also offer
products to the pharmaceutical industry
4
Dowpharma -Production of Biopharmaceuticals and
Vaccines

• Pfenex system is based on Pseudomonas fluorescens
• Emphasis has been placed on improving correct
  disulfide bond formation, reducing protease
  levels and enhancing secretion of product to give
  the highest possible yield of soluble, fully
  active protein
• Out performs E. coli in the expression of active
  soluble proteins
• Pfenex fermentations are predictably scaled at
  high density to thousands of liters in simple
  mineral salts medium without antibiotic selection
  marker

5
Periplasmic production of vaccine antigens in
Pfenex

• Complex hetero-multimeric antigen
• The large subunit contains a single disulfide
  bond
• Both subunits are secreted to the periplasm
• Both subunits are fully and correctly processed
• Both subunits assemble into fully active
  holo-multimer

• Three bacterial toxin fragments
• Non- optimized expression in Pfenex in excess
  of 1 g/L
• Roughly 5x expression reported from E coli
  inclusion bodies

6
Dow AgroSciences Plant-Cell-Produced Vaccines

• Technology relies on plant cells rather than
  whole plants for protein expression
• eliminates most risk of contamination associated
  with mammalian or avian based production
• production system is completely bio-contained
• Produces multiple subunit vaccines
• Anticipate worlds first plant-based vaccine
  license in Q4 2005 or Q1 2006 Newcastle Disease
  Virus Vaccine