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Table of ContentsTable of Contents

• The bio-manufacturing capacity squeeze

• Emerging plant-based production technology

• Pharmaceutical applications: Clinical and non-clinical

• Industrial applications

• Monoclonal antibodies (Mabs)

• Advantages of plants as factories

• Cross-pollination risk

• APHIS Best Practices

• APHIS Regulations

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The bio-manufacturing capacity squeeze

Since the human genome was deciphered, biotech products have occu-Since the human genome was deciphered, biotech products have occu-pied a growing portion of the drug discovery pipeline. pied a growing portion of the drug discovery pipeline.

BioLogic USA 2004 estimates that the biotech drug market today is worth over estimates that the biotech drug market today is worth over $40bn. According to Syngenta, $40bn. According to Syngenta, biopharmaceuticals represent the fastest growing biopharmaceuticals represent the fastest growing segment within the human therapeutic market and are expected to grow to segment within the human therapeutic market and are expected to grow to approximately one-third of the pharma market by 2010, reaching sales of $110 approximately one-third of the pharma market by 2010, reaching sales of $110 billion in United States alone.billion in United States alone.

Biotech drugs are made from recombinant therapeutic proteins, particularly Biotech drugs are made from recombinant therapeutic proteins, particularly antibodies. Because of their complexity, biopharmaceuticals need to be antibodies. Because of their complexity, biopharmaceuticals need to be synthesized by bacteria, yeast or mammalian cell-based fermentation production synthesized by bacteria, yeast or mammalian cell-based fermentation production platforms, which have inherent limitations. platforms, which have inherent limitations.

Syngenta biopharma believes that biomanufacturing in plants offer unique Syngenta biopharma believes that biomanufacturing in plants offer unique advantages for the production of some of these biopharmaceuticals. advantages for the production of some of these biopharmaceuticals.

The pipeline:The pipeline:

Depending on what you read, there are between 400 and 1200 antibody-based Depending on what you read, there are between 400 and 1200 antibody-based drugs in the R&D pipeline. The FDA has approved roughly 60 protein drugs in the R&D pipeline. The FDA has approved roughly 60 protein pharmaceuticals according to Maxygen, an industry leader whose scale-up model pharmaceuticals according to Maxygen, an industry leader whose scale-up model is based on mammalian cell expression. is based on mammalian cell expression.

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Biotech drugs Biotech drugs

Made from Made from Recombinant Therapeutic ProteinsRecombinant Therapeutic Proteins (RTPs), (RTPs), particularly antibodies. particularly antibodies.

Between 400 and 1200 antibody-based drugs in the R&D pipeline. Between 400 and 1200 antibody-based drugs in the R&D pipeline.

FDA has approved approx. 60 RTP-based pharmaceuticals.FDA has approved approx. 60 RTP-based pharmaceuticals.

Biotech drug market worth over $40bn today; sales projected to reach $110bn in the Biotech drug market worth over $40bn today; sales projected to reach $110bn in the USA by 2010 (source: Syngenta)USA by 2010 (source: Syngenta)

RTPs conventionally synthesized in bacteria, yeast or mammalian cell-based RTPs conventionally synthesized in bacteria, yeast or mammalian cell-based fermentation production platforms, fermentation production platforms, which have inherent limitationswhich have inherent limitations

• limited in size limited in size • require high CAPEX require high CAPEX • require 4 or 5 years’ lead-time to come on-streamrequire 4 or 5 years’ lead-time to come on-stream

U.S. and European companies have been operating at their capacity limits for several U.S. and European companies have been operating at their capacity limits for several yearsyears

New technology: Genetically engineeredNew technology: Genetically engineered mass-cultivation row crops like corn and mass-cultivation row crops like corn and tobacco to serve as “bio-reactors” to produce RTPstobacco to serve as “bio-reactors” to produce RTPs

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Production bottleneck: Production bottleneck:

U.S. and European companies have been operating at their U.S. and European companies have been operating at their capacity limits for several years. This, combined with the capacity limits for several years. This, combined with the avalanche of new recombinant therapeutic proteins in avalanche of new recombinant therapeutic proteins in development, is exacerbating the deficit in conventional development, is exacerbating the deficit in conventional fermentation-based production capacity. fermentation-based production capacity.

Fermentation systems have 3 drawbacks:Fermentation systems have 3 drawbacks:

(1)(1) they are limited in size; they are limited in size;

(2)(2) they require high capital expenditure (CAPEX); they require high capital expenditure (CAPEX);

(3)(3) they require 4 or 5 years’ lead-time to come on-stream. they require 4 or 5 years’ lead-time to come on-stream. According to ProdiGene, even if existing fermentation facilities According to ProdiGene, even if existing fermentation facilities increase their capacity by 3X or 4X, demand will still not be increase their capacity by 3X or 4X, demand will still not be satisfied. satisfied.

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Emerging plant-based production technology

As a result of the fermentation capacity-squeeze and the Tsunami of new As a result of the fermentation capacity-squeeze and the Tsunami of new recombinant therapeutic proteins in the global R&D pipeline, several dozen recombinant therapeutic proteins in the global R&D pipeline, several dozen companies have focused on developing an alternative to traditional companies have focused on developing an alternative to traditional fermentation methods. fermentation methods.

Mass-cultivation row crops (e.g. corn and tobacco) are being genetically Mass-cultivation row crops (e.g. corn and tobacco) are being genetically engineered to serve as factories or “bio-reactors” to produce proteins and engineered to serve as factories or “bio-reactors” to produce proteins and enzymes for pharmaceutical and industrial uses.enzymes for pharmaceutical and industrial uses.

The use of mass-cultivation row crops to produce compounds for The use of mass-cultivation row crops to produce compounds for pharmaceuticals and industry implies dramatic volume and CAPEX pharmaceuticals and industry implies dramatic volume and CAPEX advantages, primarily because scale-up simply means increasing cultivated advantages, primarily because scale-up simply means increasing cultivated acreage, to a large extent employing existing agricultural equipment and acreage, to a large extent employing existing agricultural equipment and infrastructure.infrastructure.

The reduction in front-end capital investment (by comparison to The reduction in front-end capital investment (by comparison to conventional fermentation technology) could significantly alter the future conventional fermentation technology) could significantly alter the future economics of drug production in favor of the consumer.economics of drug production in favor of the consumer.

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Pharmaceutical applications: Clinical & non-clinical

The “first wave” of clinical applications includes edible vaccines, The “first wave” of clinical applications includes edible vaccines, antibiotics, anti-HIV drugs & anti-clotting agents, among others. Edible antibiotics, anti-HIV drugs & anti-clotting agents, among others. Edible vaccines do away with needles, don’t need refrigeration and are far simpler to vaccines do away with needles, don’t need refrigeration and are far simpler to administer. They have already been developed for Hepatitis-B, bacterial Lt-B administer. They have already been developed for Hepatitis-B, bacterial Lt-B toxin that causes "Traveler's Disease” and TGVE (Transmissible Gastro-toxin that causes "Traveler's Disease” and TGVE (Transmissible Gastro-Enteritis Virus). Other clinical products in the pipeline are Albumin, Aprotinin, Enteritis Virus). Other clinical products in the pipeline are Albumin, Aprotinin, Trypsin, Lactoferrin and, significantly, monoclonal antibodies (details on next Trypsin, Lactoferrin and, significantly, monoclonal antibodies (details on next slide).slide).

Non-clinical pharmaceutical applications include intermediate products in Non-clinical pharmaceutical applications include intermediate products in pharmaceutical manufacturing, diagnostics and protein purification.pharmaceutical manufacturing, diagnostics and protein purification.

Industrial applications

Row crops are also being genetically engineered to produce industrial Row crops are also being genetically engineered to produce industrial enzymes that act as biological catalysts in mineral recovery; biodegradable enzymes that act as biological catalysts in mineral recovery; biodegradable plastics, paints & detergents; paper bleaching; food processing; leather plastics, paints & detergents; paper bleaching; food processing; leather tanning; bioremediation; enhanced performance building materials; protein-tanning; bioremediation; enhanced performance building materials; protein-based silk-like fibers; cosmetics & adhesives; sensors & analytical devices; based silk-like fibers; cosmetics & adhesives; sensors & analytical devices; and eventually, electronic components.and eventually, electronic components.

Source: Pioneer Hi-Bred & DuPontSource: Pioneer Hi-Bred & DuPont

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Monoclonal antibodies (Mabs)

Mabs are the fastest growing class of therapeutic proteins, given their Mabs are the fastest growing class of therapeutic proteins, given their relatively recent appearance on the market;relatively recent appearance on the market;

Potential application in multiple therapeutic classes (cancer, infectious Potential application in multiple therapeutic classes (cancer, infectious diseases, cardiovascular indications, autoimmune diseases); reduced diseases, cardiovascular indications, autoimmune diseases); reduced side effect profile and optimized therapeutic efficacy;side effect profile and optimized therapeutic efficacy;

Estimated 190+ Mabs now in clinical trials; +/- 350 Mabs in pre-clinical Estimated 190+ Mabs now in clinical trials; +/- 350 Mabs in pre-clinical development;development;

Mabs are highly complex proteins; cannot be effectively produced in Mabs are highly complex proteins; cannot be effectively produced in bacterial or yeast-based systems; conventionally developed in high cost bacterial or yeast-based systems; conventionally developed in high cost systems such as mammalian cells or transgenic animals;systems such as mammalian cells or transgenic animals;

Mab treatment needs large quantities (several grams per patient per Mab treatment needs large quantities (several grams per patient per day); treatment is therefore costly and points to need for additional day); treatment is therefore costly and points to need for additional production capacity.production capacity.

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Advantages of plants as factories

Plant cells are eukaryotic; they are capable of acting as efficient Plant cells are eukaryotic; they are capable of acting as efficient natural bioreactors making complex proteins with therapeutic properties natural bioreactors making complex proteins with therapeutic properties equivalent to human proteins. equivalent to human proteins.

Recent innovation in plant biotechnology (“homologous recombination”) Recent innovation in plant biotechnology (“homologous recombination”) permits targeting precisely the tissue where the protein or enzyme of permits targeting precisely the tissue where the protein or enzyme of interest will be expressed. For example, in corn the protein can be interest will be expressed. For example, in corn the protein can be selectively expressed in the grain, which translates to cost-efficient selectively expressed in the grain, which translates to cost-efficient transportation, storage, extraction, purification and delivery (i.e. optimal transportation, storage, extraction, purification and delivery (i.e. optimal OPEX). OPEX).

Since row crops have massive existing infrastructure worldwide, accelerated Since row crops have massive existing infrastructure worldwide, accelerated production ramp-ups are possible by simply increasing cultivated acreage. production ramp-ups are possible by simply increasing cultivated acreage. Consequently, plant factories will slash production lead times.Consequently, plant factories will slash production lead times.

CAPEX for plant factories is marginal by comparison to CAPEX required to CAPEX for plant factories is marginal by comparison to CAPEX required to increase conventional fermentation capacity. Reductions in CAPEX and OPEX, increase conventional fermentation capacity. Reductions in CAPEX and OPEX, taken together, may bring dramatic cost benefits to the consumer.taken together, may bring dramatic cost benefits to the consumer.

No known plant pathogens infect animals or humans, virtually eliminating No known plant pathogens infect animals or humans, virtually eliminating risk of contamination from animals.risk of contamination from animals.

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Cross-pollination risk

Cross-pollination can occur between pharmacrops and conventional Cross-pollination can occur between pharmacrops and conventional crops for human & animal consumption, which could lead to as-of-yet crops for human & animal consumption, which could lead to as-of-yet unmeasured health hazards.unmeasured health hazards.

Although genetic engineering that codes for male sterility in plants will in the long Although genetic engineering that codes for male sterility in plants will in the long run resolve this issue squarely, such genetic modification does not yet run resolve this issue squarely, such genetic modification does not yet characterize all pharmacrops. Therefore, the risk of cross-pollination remains a characterize all pharmacrops. Therefore, the risk of cross-pollination remains a top priority issue that must be very carefully managed.top priority issue that must be very carefully managed.

In 2003, an incident involving ProdiGene raised cross-pollination alarm bells In 2003, an incident involving ProdiGene raised cross-pollination alarm bells throughout the biotech and environmental communities: 500 thousand bushels of throughout the biotech and environmental communities: 500 thousand bushels of soybeans were mixed with corn that was genetically engineered to produce an soybeans were mixed with corn that was genetically engineered to produce an experimental drug. ProdiGene was fined $3 MM and legal action was taken experimental drug. ProdiGene was fined $3 MM and legal action was taken against the US Govt. by an environmental coalition seeking to ban open-field against the US Govt. by an environmental coalition seeking to ban open-field pharmacrop trials. pharmacrop trials.

The U.S. National Academy of Sciences publicly warned about infiltration of bio-The U.S. National Academy of Sciences publicly warned about infiltration of bio-pharmaceutical products into the food supply due to lax USDA regulations. The pharmaceutical products into the food supply due to lax USDA regulations. The USDA responded by issuing new safety regulations:USDA responded by issuing new safety regulations:

Inspecting test plots 5 times per growing season instead of onceInspecting test plots 5 times per growing season instead of once Greater separation distances between conventional crops and pharmacropsGreater separation distances between conventional crops and pharmacrops Mandatory separate storage, planting & harvesting equipmentMandatory separate storage, planting & harvesting equipment

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APHIS Best Practices

On 4/22/04 Director of APHIS Biotechnology Regulatory Service, Neil On 4/22/04 Director of APHIS Biotechnology Regulatory Service, Neil Hoffman Ph.D, presented BRS Hoffman Ph.D, presented BRS Best Practice Guidelines Best Practice Guidelines at the Risk at the Risk Assessment Symposium for Corn-Produced Pharmaceuticals and Assessment Symposium for Corn-Produced Pharmaceuticals and Industrials, sponsored by Industrials, sponsored by BIGMAP, the Biosafety Institute for Genetically , the Biosafety Institute for Genetically Modified Agricultural Product, a dependence of Iowa State University.Modified Agricultural Product, a dependence of Iowa State University.

The APHIS Best Practice Guidelines address confinement principles, The APHIS Best Practice Guidelines address confinement principles, segregation, non-target affects, contracting, training, site planning, segregation, non-target affects, contracting, training, site planning, security, labeling, crop selection, production planning, IP, disposal, security, labeling, crop selection, production planning, IP, disposal, documentation, compliance, monitoring & remediation, and testing documentation, compliance, monitoring & remediation, and testing alternatives (PCR vs immunological).alternatives (PCR vs immunological).

APHIS Best Practice Guidelines stress criticality of IP APHIS Best Practice Guidelines stress criticality of IP programming throughout the lifecycle of pharmacrops, and thus programming throughout the lifecycle of pharmacrops, and thus implies that we should carve a niche that will grow pari-passu implies that we should carve a niche that will grow pari-passu market growthmarket growth. .

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APHIS regulations

[Docket No. 03-031-1] March 10, 2003 Federal Register Vol. 68, No 46 Governs field testing Governs field testing of plants engineered to produce pharmaceutical and of plants engineered to produce pharmaceutical and industrial compounds. APHIS authorized over 1000 field tests in 2002, of industrial compounds. APHIS authorized over 1000 field tests in 2002, of which fewer than 20 field test permits were for pharmacrops planted at 34 which fewer than 20 field test permits were for pharmacrops planted at 34 sites totaling about 130 acres (generally less than 5 acres per site)sites totaling about 130 acres (generally less than 5 acres per site)

[Docket No. 03-038-1] August 6 2003 Federal Register Vol. 68, No 151Compounds for industrial use:Compounds for industrial use: Interim regulation till 12/31/04, mandates Interim regulation till 12/31/04, mandates prior government permitprior government permit for introduction of plants genetically engineered to for introduction of plants genetically engineered to encode industrial compounds. Only 10 applications were submitted to encode industrial compounds. Only 10 applications were submitted to introduce plants producing industrial compounds in the 10 year period introduce plants producing industrial compounds in the 10 year period 1993-2003. 5 permit applications were submitted in the 6 months between 1993-2003. 5 permit applications were submitted in the 6 months between Aug 2003 & Jan 2004.Aug 2003 & Jan 2004.

[Docket No. 03-031-2] January 23, 2004 Federal Register Vol. 69, No 15Environmental Impact StatementEnvironmental Impact Statement (EIS) will address new trends including the use of (EIS) will address new trends including the use of genetically engineered plants to produce pharmaceutical and industrial compounds.genetically engineered plants to produce pharmaceutical and industrial compounds.

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The approval process for the introduction of GM plants for pharma The approval process for the introduction of GM plants for pharma or industrial uses takes 3+ months. or industrial uses takes 3+ months.

Upon receiving applications, APHIS scientists review for Upon receiving applications, APHIS scientists review for deficiencies. If deficiencies are found the applicant is given the deficiencies. If deficiencies are found the applicant is given the opportunity to respond, and the permit is either issued or denied opportunity to respond, and the permit is either issued or denied within 120 days. within 120 days.

If applications are approved, the permit and associated conditions If applications are approved, the permit and associated conditions are sent to the State (s) in which the introduction would occur. The are sent to the State (s) in which the introduction would occur. The State (s) may concur, or add conditions and concur. State (s) may concur, or add conditions and concur.

Authorizations require compliance with standard permit Authorizations require compliance with standard permit conditions, plus supplemental conditions based on risks involved in conditions, plus supplemental conditions based on risks involved in each case.each case.

APHIS Biotechnology – site map

Current Status of APHIS approvals

APHIS permitting process

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Market makers

Research conducted by Freedonia, Theta and Drug & Market Development Research conducted by Freedonia, Theta and Drug & Market Development Corp. estimate that ~60 private companies Corp. estimate that ~60 private companies and ~60 research institutes worldwideand ~60 research institutes worldwide are involved in biopharming R&D are involved in biopharming R&D with a strong product development pipeline, active field trials, advanced with a strong product development pipeline, active field trials, advanced regulatory approvals and affiliations to leading grain or seed companies. regulatory approvals and affiliations to leading grain or seed companies.

These are the some of the high profile players.These are the some of the high profile players.

BASF Plant ScienceBASF Plant Science SyngentaSyngenta Biotechnology Biotechnology

DupontDupont

Pioneer Hi-BredPioneer Hi-BredBayer Bayer CropScienceCropScience Dow Dow AgroSciencesAgroSciences

ExelixisExelixis Plant Sciences Plant Sciences VentriaVentria Bioscience Bioscience BiolexBiolex MeristemMeristem SemBioSysSemBioSys

VereniumVerenium MetabolixMetabolix EdenSpaceEdenSpace PhytomedicsPhytomedics Iowa State UIowa State U..

DOE DOE Genomics:GTLGenomics:GTL Mendel BiotechnologyMendel Biotechnology Icon GeneticsIcon Genetics Large Scale Biology CorpLarge Scale Biology Corp CeresCeres

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MERISTEM® THERAPEUTICS

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Meristem was founded in 1997 to implement the Molecular Pharming® Meristem was founded in 1997 to implement the Molecular Pharming® plant genetics program initiated in 1992 by LIMAGRAIN, the world’s 2plant genetics program initiated in 1992 by LIMAGRAIN, the world’s 2ndnd largest seed company. Meristem has contractual access to Limagrain’s largest seed company. Meristem has contractual access to Limagrain’s infrastructure, in-field production know-how, patented germplasm, and plant male infrastructure, in-field production know-how, patented germplasm, and plant male sterility anti-pollen dispersal technology. As well, via R&D in- and out-licensing sterility anti-pollen dispersal technology. As well, via R&D in- and out-licensing agreements there are regular exchanges of scientific information with Limagrain.agreements there are regular exchanges of scientific information with Limagrain.

Meristem was 1st to extract and purify active human haemoglobin in plant cells. Meristem was 1st to extract and purify active human haemoglobin in plant cells.

Meristem employs 40 scientists. The HQ, pilot production plant and research labs Meristem employs 40 scientists. The HQ, pilot production plant and research labs are located in are located in Clermont-Ferrand, in the south central region of France. The , in the south central region of France. The company has raised Euro 40+ million from life science investors led by Banexi company has raised Euro 40+ million from life science investors led by Banexi Ventures Partners. Ventures Partners.

Meristem holds patents covering production and isolation of particular classes of Meristem holds patents covering production and isolation of particular classes of recombinant proteins from plants, extraction and purification processes, promoters recombinant proteins from plants, extraction and purification processes, promoters and vectors for increased expression of recombinant proteins, and increased and vectors for increased expression of recombinant proteins, and increased biomass production & inhibition of germination in the field.biomass production & inhibition of germination in the field.

Meristem’s Molecular Pharming® technology can produce recombinant proteins Meristem’s Molecular Pharming® technology can produce recombinant proteins from the gene up to production of several tons of purified active substances. The from the gene up to production of several tons of purified active substances. The platform offers several comparative advantages for the production of complex platform offers several comparative advantages for the production of complex therapeutic proteins -including antibodies- in terms of biological safety, volume, therapeutic proteins -including antibodies- in terms of biological safety, volume, cost, speed of production and scale-up. cost, speed of production and scale-up.

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Meristem’s most advanced compound is gastric lipase, used in the Meristem’s most advanced compound is gastric lipase, used in the treatment of Exocrine Pancreatitis Insufficiency, a digestive disorder treatment of Exocrine Pancreatitis Insufficiency, a digestive disorder afflicting cystic fibrosis patients. Other compounds in the pipeline are human afflicting cystic fibrosis patients. Other compounds in the pipeline are human serum albumin (HSA), lactoferrin, collagen, monoclonal antibodies and serum albumin (HSA), lactoferrin, collagen, monoclonal antibodies and recombinant allergen from dust mites. recombinant allergen from dust mites.

Meristem holds various license and/or research agreements with:Meristem holds various license and/or research agreements with:

INSTITÜT FUR BOTANIK (Münster, Germany) for the glycosylation of INSTITÜT FUR BOTANIK (Münster, Germany) for the glycosylation of recombinant proteins in plants; recombinant proteins in plants;

JAPAN TOBACCO for the introduction of JAPAN TOBACCO for the introduction of Agrobacterium tumefaciens Agrobacterium tumefaciens bacteria bacteria gene constructs into plant cells; gene constructs into plant cells;

PANGENE for the use of their homologous recombination technique for the PANGENE for the use of their homologous recombination technique for the expression of HSA in plants; expression of HSA in plants;

MOGEN LICENSING (now Syngenta) for the use of a binary vector plasmid-MOGEN LICENSING (now Syngenta) for the use of a binary vector plasmid-based technique for the introduction of specific genes into plant cells;based technique for the introduction of specific genes into plant cells;

CALGENE (now part of MONSANTO) for research and production of proteins in CALGENE (now part of MONSANTO) for research and production of proteins in plants; plants;

CORNELL RESEARCH FOUNDATION for the use of its rice actin gene and CORNELL RESEARCH FOUNDATION for the use of its rice actin gene and promoter.promoter.

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For the in-house product pipelineFor the in-house product pipeline, Meristem undertakes the pre-, Meristem undertakes the pre-clinical and early clinical development phases, then licenses-out to clinical and early clinical development phases, then licenses-out to pharmaceutical and biotechnology partners (as it has already done for pharmaceutical and biotechnology partners (as it has already done for lipase) before the completion of phase II clinical trials, but retaining lipase) before the completion of phase II clinical trials, but retaining responsibility for production scale-up as well as ownership of the Drug responsibility for production scale-up as well as ownership of the Drug Master File. Under its agreement with QUINTILES, it now has the option Master File. Under its agreement with QUINTILES, it now has the option to continue the development of selected products through later stage to continue the development of selected products through later stage clinical trials, or right through to market approval, at which point a clinical trials, or right through to market approval, at which point a marketing partner will be sought.  marketing partner will be sought.  

For 3For 3rdrd party products party products, Meristem offers pharmaceutical and , Meristem offers pharmaceutical and biotechnology companies contract research, development and biotechnology companies contract research, development and production agreements to co-develop and ultimately manufacture the production agreements to co-develop and ultimately manufacture the proteins invented and patented by them, including monoclonal proteins invented and patented by them, including monoclonal antibodies.antibodies.

Meristem has the world's 1st kilogram-scale pilot facility for the extrac-Meristem has the world's 1st kilogram-scale pilot facility for the extrac-tion and purification of pharmaceutical grade plant-derived recombinant tion and purification of pharmaceutical grade plant-derived recombinant proteins. The facility is able to purify up to 350 grams of lipase per week proteins. The facility is able to purify up to 350 grams of lipase per week (corresponds to processing 700 kilos maize) or up to 20 kilos of purified (corresponds to processing 700 kilos maize) or up to 20 kilos of purified lipase per year.lipase per year.

MERISTEM®'s strategy is to apply its Molecular Pharming® technology and MERISTEM®'s strategy is to apply its Molecular Pharming® technology and phyto-pharmaceutical expertise to develop in-house products and 3rd party phyto-pharmaceutical expertise to develop in-house products and 3rd party products.products.

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Meristem successfully produced milligram quantities of complete and Meristem successfully produced milligram quantities of complete and conform monoclonal antibodies in tobacco. It forecasts manufacturing conform monoclonal antibodies in tobacco. It forecasts manufacturing monoclonal antibodies at a cost similar to other recombinant proteins monoclonal antibodies at a cost similar to other recombinant proteins in its development pipeline, which could reduce cost by as much as 5-10 in its development pipeline, which could reduce cost by as much as 5-10 times by comparison to existing technologies. 5-10X savings should apply to all times by comparison to existing technologies. 5-10X savings should apply to all monoclonal antibodies in the same class (IgG, IgE, IgA) since within a given class monoclonal antibodies in the same class (IgG, IgE, IgA) since within a given class antibodies share almost entirely the same protein chain configuration.antibodies share almost entirely the same protein chain configuration.

Multiple-year authorizations for in-field production of crops have been obtained Multiple-year authorizations for in-field production of crops have been obtained in France for tobacco and corn. Meristem also produces in Spain, the USA and in France for tobacco and corn. Meristem also produces in Spain, the USA and Chile. By alternating the growing seasons between France, Spain, Chile and the Chile. By alternating the growing seasons between France, Spain, Chile and the USA, multiple production cycles are possible each year. USA, multiple production cycles are possible each year.

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Verdia, Inc.

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Verdia was established in 1999. In July 2004 DuPont acquired Verdia Verdia was established in 1999. In July 2004 DuPont acquired Verdia from Maxygen (Nasdaq: from Maxygen (Nasdaq: MAXY) for $64 MM. ) for $64 MM.

Verdia’s MolecularBreeding™ technology is designed to Verdia’s MolecularBreeding™ technology is designed to direct molecular evolutiondirect molecular evolution to optimize input traits (disease, herbicide & pest resistance) and output traits to optimize input traits (disease, herbicide & pest resistance) and output traits (nutritional value) through high throughput (HTP) assays that selectively (nutritional value) through high throughput (HTP) assays that selectively “interrogate” microbial and plant diversity, and then predict the efficiency of the “interrogate” microbial and plant diversity, and then predict the efficiency of the genetic material’s coding for the expression of targeted traits. DuPont says that genetic material’s coding for the expression of targeted traits. DuPont says that MolecularBreeding™ technology will allow it to accelerate its gene research MolecularBreeding™ technology will allow it to accelerate its gene research targets by as much as 3 years.targets by as much as 3 years.

Verdia’s focus is on developing novel input traits for the major row crops – corn, Verdia’s focus is on developing novel input traits for the major row crops – corn, soybean & cotton - as genetic alternatives to the $28 billion crop protection soybean & cotton - as genetic alternatives to the $28 billion crop protection chemical market. Three pipeline projects - biofuels, specialty chemicals & chemical market. Three pipeline projects - biofuels, specialty chemicals & enabling technologies - appear oriented toward industrial compounds.enabling technologies - appear oriented toward industrial compounds.

The raw genetic material chosen for HTP assay is sourced either from biodiversity The raw genetic material chosen for HTP assay is sourced either from biodiversity around the globe, in-licensing or the public domain. Initial selection of un-assayed around the globe, in-licensing or the public domain. Initial selection of un-assayed gene material depends on market opportunity, commercial potential, technical gene material depends on market opportunity, commercial potential, technical feasibility and the competitive landscape.feasibility and the competitive landscape.

Once HTP assays have predicted which genetic material most efficiently codes for Once HTP assays have predicted which genetic material most efficiently codes for desired traits, single or multiple genes are recombined in 2 discrete “desired traits, single or multiple genes are recombined in 2 discrete “trait trait optimizationoptimization” steps - “DNA Reshuffling” and “MaxyScan™”. ” steps - “DNA Reshuffling” and “MaxyScan™”.

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Traits expressed by reshuffled genes are validated in-greenhouse Traits expressed by reshuffled genes are validated in-greenhouse using model plants like tobacco or using model plants like tobacco or Arabidopsis ThalianaArabidopsis Thaliana, a weed , a weed intensely studied by researchers due to its rapid growth and compact intensely studied by researchers due to its rapid growth and compact genome.genome.

Reshuffled genes that meet selection criteria are integrated in row crop Reshuffled genes that meet selection criteria are integrated in row crop germplasm and tested in-field, germplasm and tested in-field, typically by Verdia’s partners or 3rd party typically by Verdia’s partners or 3rd party contract research developerscontract research developers..

Scientists at Verdia and Pioneer Hi-Bred developed the first agricultural trait Scientists at Verdia and Pioneer Hi-Bred developed the first agricultural trait developed through gene shuffling.developed through gene shuffling.

Product pipeline: includes 20 product candidates with a potential technology Product pipeline: includes 20 product candidates with a potential technology value of over $2.8 billion. 7 products are in commercial development with its value of over $2.8 billion. 7 products are in commercial development with its sister company Pioneer Hi-Bred International, and with Syngenta.sister company Pioneer Hi-Bred International, and with Syngenta.

Intellectual property: Verdia has filed 11 U.S. patent applications on its Intellectual property: Verdia has filed 11 U.S. patent applications on its technologies and products. Verdia has also licensed 55 issued U.S. patents, 32 technologies and products. Verdia has also licensed 55 issued U.S. patents, 32 issued foreign patents and approximately 200 pending U.S. and foreign issued foreign patents and approximately 200 pending U.S. and foreign applications. applications.

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VERENIUM

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Verenium (Nasdaq: VRNM) emerged from the merger between Verenium (Nasdaq: VRNM) emerged from the merger between Diversa and Celunol. Diversa and Celunol.

VereniumVerenium develops small molecules and enzymes for chemical process, develops small molecules and enzymes for chemical process, industrial, agricultural and pharmaceutical applications.industrial, agricultural and pharmaceutical applications.

Verenium sources genetic material from global microbial bio-diversity as Verenium sources genetic material from global microbial bio-diversity as far reaching as geothermal and hydrothermal vents, boiling mud pots, far reaching as geothermal and hydrothermal vents, boiling mud pots, alkaline springs, manure piles, contaminated industrial sites, Arctic alkaline springs, manure piles, contaminated industrial sites, Arctic tundra, dry Antarctic valleys, super cooled sea ice, microbial mats, tundra, dry Antarctic valleys, super cooled sea ice, microbial mats, bacterial communities associated with insects, nematodes, fungi and bacterial communities associated with insects, nematodes, fungi and plant endophytes. It then applies ultra high-throughput (UHTP) screening plant endophytes. It then applies ultra high-throughput (UHTP) screening and gene shuffling technology to discover novel “natural” compounds.and gene shuffling technology to discover novel “natural” compounds.

Verenium’s process has 2 advantages by comparison to lab-based Verenium’s process has 2 advantages by comparison to lab-based synthesis: synthesis:

(1)(1) Nature produces more complex/sophisticated chemical structures Nature produces more complex/sophisticated chemical structures with a broader range of possible applications; with a broader range of possible applications;

(2)(2) it leverages the characteristics of molecules that have been pre-it leverages the characteristics of molecules that have been pre-selected in the environment to perform specific biological functions.selected in the environment to perform specific biological functions.

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Verenium’s Verenium’s GigaMatrix™ ultra ™ ultra high-throughput screening high-throughput screening platform uses plates with a platform uses plates with a 100,000-well density contained in 100,000-well density contained in the same 3.3” x 5” foot-print of a the same 3.3” x 5” foot-print of a standard plate, making it standard plate, making it exponentially more efficient than exponentially more efficient than standard 96-, 384-, or 1536-well standard 96-, 384-, or 1536-well screening systems. screening systems.

Each GigaMatrixEach GigaMatrix well has a well has a diameter of a human hair, is diameter of a human hair, is reusable and requires minuscule reusable and requires minuscule reagent volume, making the reagent volume, making the system highly cost effective.system highly cost effective.

GigaMatrix is capable of screening GigaMatrix is capable of screening one billion clones per day, permits one billion clones per day, permits rapid screening of genes and gene rapid screening of genes and gene pathways, thus maximizing the pathways, thus maximizing the productivityproductivity of novel enzyme & novel enzyme & small molecule drug discovery. small molecule drug discovery.

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Biolex

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Biolex is a private company focused on developing recombinant Biolex is a private company focused on developing recombinant therapeutic proteins and monoclonal antibodies by leveraging the therapeutic proteins and monoclonal antibodies by leveraging the natural characteristics of the small green aquatic plant, natural characteristics of the small green aquatic plant, Lemna..

Biolex has a proprietary genetic engineering and protein recovery LEX System™ Biolex has a proprietary genetic engineering and protein recovery LEX System™ that can escalate a protein from amino acid sequence to purified product for that can escalate a protein from amino acid sequence to purified product for clinical trials and commercial supply.clinical trials and commercial supply. Biolex is funded by a syndicate of life science venture firms and strategic Biolex is funded by a syndicate of life science venture firms and strategic investors including Johnson & Johnson and Dow. investors including Johnson & Johnson and Dow.

Biolex CEO Jan Turek was formerly global head of Bayer’s Biological Products Biolex CEO Jan Turek was formerly global head of Bayer’s Biological Products Business Unit. Business Unit.

Lemna has various important comparative advantages in comparison to field crop Lemna has various important comparative advantages in comparison to field crop and animal-based transgenic production systems: and animal-based transgenic production systems:

Plant replication without pollen or seedsPlant replication without pollen or seeds Fast growth rate, with biomass doubling every 36 hoursFast growth rate, with biomass doubling every 36 hours High protein content resulting in high expression levelsHigh protein content resulting in high expression levels Secretes target protein into an easily purified mediumSecretes target protein into an easily purified medium Contrary to filed crops, production is in a contained & controlled facilityContrary to filed crops, production is in a contained & controlled facility Previous point permits high conformance to regulatory requirementsPrevious point permits high conformance to regulatory requirements Scale up is quick and predictableScale up is quick and predictable

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The natural characteristics of The natural characteristics of LemnaLemna coupled with the contained coupled with the contained LEX System™ avoids most of the environmental risks associated LEX System™ avoids most of the environmental risks associated with plant-manufactured pharmaceuticals. with plant-manufactured pharmaceuticals.

Biolex has established partnerships with top-tier pharmaceutical and Biolex has established partnerships with top-tier pharmaceutical and biotechnology companies including Bayer. biotechnology companies including Bayer.

In 2004 Biolex In 2004 Biolex acquired Epicyte Pharmaceuticals which specializes in the which specializes in the discovery and development of human monoclonal antibodies, having successfully discovery and development of human monoclonal antibodies, having successfully expressed (in corn) an antibody for protection against herpes simplex virus expressed (in corn) an antibody for protection against herpes simplex virus infections.infections.

Biolex owns cGMP manufacturing operations in Pittsboro, North Carolina. Alpha Biolex owns cGMP manufacturing operations in Pittsboro, North Carolina. Alpha Interferon-2b is in development as the first Biolex Protein, for which human clinical Interferon-2b is in development as the first Biolex Protein, for which human clinical trials began in 2004. trials began in 2004.

The 20+ human therapeutic proteins Biolex has attempted to-date have been The 20+ human therapeutic proteins Biolex has attempted to-date have been expressed successfully in the LEX System™. expressed successfully in the LEX System™.

Each of the proteins has the predicted composition, desired physical structure and Each of the proteins has the predicted composition, desired physical structure and correct biological activity.correct biological activity.

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Exelixis Plant Sciences

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Exelixis (Exelixis (Nasdaq: EXEL) is focused on the discovery and development ) is focused on the discovery and development of new drug therapies for cancer and other proliferative diseases. of new drug therapies for cancer and other proliferative diseases.

The company leverages an integrated gene-to-drug platform that The company leverages an integrated gene-to-drug platform that moves from DNA data to gene protein functionality quickly and cost moves from DNA data to gene protein functionality quickly and cost effectively.effectively.

Exelixis has partnerships with Bayer CropScience, Dow AgroSciences, Exelixis has partnerships with Bayer CropScience, Dow AgroSciences, Bristol-Myers Squibb, Merck, Pharmacia, Schering-Plough, among Bristol-Myers Squibb, Merck, Pharmacia, Schering-Plough, among others. others.

After acquiring Agritope Inc. in 2000, Exelixis formed After acquiring Agritope Inc. in 2000, Exelixis formed Exelixis Plant Exelixis Plant SciencesSciences to expand its access to plant model system technologies to expand its access to plant model system technologies and product development. and product development.

Exelixis Plant Sciences focuses on model plant systems like Exelixis Plant Sciences focuses on model plant systems like Arabidopsis, tomato and rice, to produce high value compounds like Arabidopsis, tomato and rice, to produce high value compounds like natural flavors and colorants for the packaged foods and cosmetics natural flavors and colorants for the packaged foods and cosmetics industries, as well as pharmaceuticals.industries, as well as pharmaceuticals.

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To tap naturally occurring plant compounds, Exelixis Plant Sciences To tap naturally occurring plant compounds, Exelixis Plant Sciences developed assays to identify the genetic mechanisms that control the developed assays to identify the genetic mechanisms that control the production of these compounds. production of these compounds.

Using a combination of model plant species and proprietary gene Using a combination of model plant species and proprietary gene discovery technology, robotics and high-throughput biochemical discovery technology, robotics and high-throughput biochemical assays, Exelixis Plant Sciences has discovered novel mechanisms for assays, Exelixis Plant Sciences has discovered novel mechanisms for controlling the production of valuable naturally occurring compounds controlling the production of valuable naturally occurring compounds including natural colorants for the cosmetics and textiles industries including natural colorants for the cosmetics and textiles industries and natural flavors for the packaged food industry.and natural flavors for the packaged food industry.

Exelixis’ proprietary gene discovery technology has been developed Exelixis’ proprietary gene discovery technology has been developed through Agrinomics LLC, a 50-50 joint venture between Exelixis and through Agrinomics LLC, a 50-50 joint venture between Exelixis and Bayer CropScience. Bayer CropScience.

The gene discovery technology uses a positive genetic trait The gene discovery technology uses a positive genetic trait identification methodology known as “activation tagging” (ACTTAG™) identification methodology known as “activation tagging” (ACTTAG™) to identify gain-of-function and loss-of-function mutations and to to identify gain-of-function and loss-of-function mutations and to permit up-regulation or over-expression as vehicles for plant trait permit up-regulation or over-expression as vehicles for plant trait modification.modification.

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Large Scale Biology Corporation

(LSBC)

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Large Scale Biology Corporation (LSBC) produces biopharmaceuticals Large Scale Biology Corporation (LSBC) produces biopharmaceuticals and other commercial proteins from plants using its GENEWARE® and other commercial proteins from plants using its GENEWARE® technology platform that comprises industrial-scale processes for technology platform that comprises industrial-scale processes for the extraction and purification of proteins, peptides and other the extraction and purification of proteins, peptides and other biochemicals from plant biomass, mainly tobacco.biochemicals from plant biomass, mainly tobacco.

LSBC believes GENEWARE® provides the quickest, safest, most economic and LSBC believes GENEWARE® provides the quickest, safest, most economic and highest-throughput technique for manufacturing proteins from their encoding highest-throughput technique for manufacturing proteins from their encoding genes, offering commercial advantages over traditional protein manufacturing genes, offering commercial advantages over traditional protein manufacturing methods such as E. coli fermentation, mammalian cell culture and transgenic methods such as E. coli fermentation, mammalian cell culture and transgenic animals.animals.

The company has a 27,000 square footThe company has a 27,000 square foot production facility in Owensboro, Kentucky, production facility in Owensboro, Kentucky, used to produce commercial quantities of recombinant crops and a range of used to produce commercial quantities of recombinant crops and a range of therapeutics including peptides, enzymes and vaccines.therapeutics including peptides, enzymes and vaccines.

LSBC has strong intellectual property protection through 52 issued US patents and LSBC has strong intellectual property protection through 52 issued US patents and 109 pending US patents, plus 49 issued and 146 pending foreign patents. 109 pending US patents, plus 49 issued and 146 pending foreign patents.

Since the summer of 2000, LSBC has been using tobacco plants to produce Since the summer of 2000, LSBC has been using tobacco plants to produce individualized therapeutic vaccines to treat patients with B-cell non-Hodgkin’s individualized therapeutic vaccines to treat patients with B-cell non-Hodgkin’s lymphoma (NHL).lymphoma (NHL).

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LSBC is aiming at developing personalized medicine tailored to the LSBC is aiming at developing personalized medicine tailored to the specific needs of patient populations or even individual patients. specific needs of patient populations or even individual patients. LSBC believes this approach will become a key driving force in 21LSBC believes this approach will become a key driving force in 21stst century medicine and pharmaceutical development. century medicine and pharmaceutical development.

As human diseases typically involve abnormalities in protein expression, As human diseases typically involve abnormalities in protein expression, discovering such abnormalities is LSBC’s first step in identifying new molecular discovering such abnormalities is LSBC’s first step in identifying new molecular targets for therapeutic drugs. targets for therapeutic drugs.

To find disease-related proteins, healthy and diseased tissue samples are To find disease-related proteins, healthy and diseased tissue samples are compared using LSBC’s ProGEx™ technology that combines extreme sensitivity compared using LSBC’s ProGEx™ technology that combines extreme sensitivity with industrial scale reproducible analysis.with industrial scale reproducible analysis.

Potential protein targets have been identified across a spectrum of disease Potential protein targets have been identified across a spectrum of disease areas, including depression, raised cholesterol, osteoporosis, osteoarthritis, areas, including depression, raised cholesterol, osteoporosis, osteoarthritis, obesity, diabetes and cardiovascular disease.obesity, diabetes and cardiovascular disease.

LSBC has collaboration agreements with Agilent, Dow, GlaxoSmithKline, LSBC has collaboration agreements with Agilent, Dow, GlaxoSmithKline, National Institute of Environmental Health Sciences, National Institute of National Institute of Environmental Health Sciences, National Institute of Standards and Technology (NIST), National University of Singapore, Novozymes, Standards and Technology (NIST), National University of Singapore, Novozymes, U.S. Navy, University of Arkansas for Medical Sciences, University of Cape Town, U.S. Navy, University of Arkansas for Medical Sciences, University of Cape Town, University of South Florida, the Government of Ukraine and Weyerhaeuse, University of South Florida, the Government of Ukraine and Weyerhaeuse, among others.among others.

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Ventria Bioscience

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Ventria Bioscience, headquartered in Sacramento, California, has Ventria Bioscience, headquartered in Sacramento, California, has created a rich product pipeline in human nutrition, human therapeutics created a rich product pipeline in human nutrition, human therapeutics and animal health, through internal R&D and collaborations with world-and animal health, through internal R&D and collaborations with world-renowned biotech and industry leaders. renowned biotech and industry leaders.

The company is led by renowned The company is led by renowned Board of Directors, an experienced , an experienced management team, a rich , a rich scientific network and leading-edge scientists who, prior and leading-edge scientists who, prior to joining Ventria, had accumulated over 120 years of biotech experience, to joining Ventria, had accumulated over 120 years of biotech experience, registered 145 U.S. and foreign registered 145 U.S. and foreign patents, and published over 600 , and published over 600 scientific papers..

Among others, Ventria has strategic partnerships with Procter & Gamble, Sigma-Among others, Ventria has strategic partnerships with Procter & Gamble, Sigma-Aldrich Fine Chemicals and Sioux Pharm Inc. Aldrich Fine Chemicals and Sioux Pharm Inc.

In 1997 Ventria's scientists developed a breakthrough protein/peptide expression In 1997 Ventria's scientists developed a breakthrough protein/peptide expression technology, “ExpressTec”, whose cost-efficiency and proven commercial scalability technology, “ExpressTec”, whose cost-efficiency and proven commercial scalability addresses under-served needs in human and animal health, by delivering addresses under-served needs in human and animal health, by delivering affordableaffordable treatments on a global scale. treatments on a global scale.

ExpressTec production includes ExpressTec production includes lactoferrin and and lysozyme, both proteins that can be , both proteins that can be administered orally or topically in a variety of human and animal health administered orally or topically in a variety of human and animal health applications. Metric-ton quantities for these products are in demand worldwide, yet applications. Metric-ton quantities for these products are in demand worldwide, yet they have proven costly or impossible to produce in traditional production systems they have proven costly or impossible to produce in traditional production systems like bacteria, yeast or fungi.like bacteria, yeast or fungi.

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Economically advantaged expression capability (e.g. 10g/kg of brown rice)Economically advantaged expression capability (e.g. 10g/kg of brown rice) Proven scalability for large volumes of recombinant proteins/peptides with Proven scalability for large volumes of recombinant proteins/peptides with

minimal capital investment compared with other systemsminimal capital investment compared with other systems Free of infectious or toxic contaminantsFree of infectious or toxic contaminants Self-pollinating crops provide a safe and closed production systemSelf-pollinating crops provide a safe and closed production system Efficient supply management since the protein/peptide can be stored in its Efficient supply management since the protein/peptide can be stored in its lowest cost form for multiple yearslowest cost form for multiple years Utilizes a proven production and processing infrastructureUtilizes a proven production and processing infrastructure

ExpressTec uses self-pollinating crops (rice and barley) as the (rice and barley) as the production host for these products, bypassing many of the production host for these products, bypassing many of the technological constraints inherent in other protein production technological constraints inherent in other protein production methods. methods.

The key benefits are:The key benefits are:

ExpressTec is versatile, expressing the following range of molecules:ExpressTec is versatile, expressing the following range of molecules:

Large molecules (larger than 50 kD)Large molecules (larger than 50 kD) Small molecules (less than 10 kD)Small molecules (less than 10 kD) Multiple sub-unit molecules (e.g. fibrinogen) Multiple sub-unit molecules (e.g. fibrinogen) Structural/functional proteins or enzymesStructural/functional proteins or enzymes Products resulting from metabolic engineeringProducts resulting from metabolic engineering

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Syngenta

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Headquartered in Basel, Switzerland, Syngenta is a world leader in Headquartered in Basel, Switzerland, Syngenta is a world leader in agribusiness crop protection, ranking 3rd in the commercial seeds agribusiness crop protection, ranking 3rd in the commercial seeds market. Sales in 2003 were approximately US$ 6.6 billion. Syngenta market. Sales in 2003 were approximately US$ 6.6 billion. Syngenta employs some 19,000 people in over 90 countries. Syngenta is listed on the employs some 19,000 people in over 90 countries. Syngenta is listed on the Swiss stock exchange (SYNN) and in New York (Swiss stock exchange (SYNN) and in New York (SYT).).

Since May 2004 Syngenta is the process of acquiring Advanta, the 5th largest Since May 2004 Syngenta is the process of acquiring Advanta, the 5th largest agricultural seed company in the world.agricultural seed company in the world. AdvantaAdvanta is ais a Dutch company owned by Dutch company owned by AstraZeneca (UK) and Royal Cosun (Netherlands). Both the E.U. and the US AstraZeneca (UK) and Royal Cosun (Netherlands). Both the E.U. and the US Department of Justice have approved the deal, structured as follows:Department of Justice have approved the deal, structured as follows:

Syngenta will acquire all the shares of Advanta BVSyngenta will acquire all the shares of Advanta BV

Syngenta will retain Advanta’s North American corn and soybean Syngenta will retain Advanta’s North American corn and soybean business plus Agripro Wheatbusiness plus Agripro Wheat

Syngenta will sell the rest of Advanta’s worldwide business to Fox Paine Syngenta will sell the rest of Advanta’s worldwide business to Fox Paine & Company, a private equity company based in Foster City, CA, with US & Company, a private equity company based in Foster City, CA, with US $ 1.5+ billion under management$ 1.5+ billion under management

Fox Paine will also take a 10% share in the Advanta North American Fox Paine will also take a 10% share in the Advanta North American business that will be retained by Syngenta business that will be retained by Syngenta

The acquisition of the North American corn and soybean business of Advanta is The acquisition of the North American corn and soybean business of Advanta is expected to increase Syngenta’s share in the US corn market to more than 10% expected to increase Syngenta’s share in the US corn market to more than 10% and broaden Syngenta’s germplasm base and enhance its platform for and broaden Syngenta’s germplasm base and enhance its platform for biotechnology products. biotechnology products.

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The Syngenta genealogy…

1758 Geigy founded

1876 Sandoz founded

1884 Ciba established

1926 Imperial Chemical Industries (ICI) formed through merger

1970 Ciba and Geigy merge to form Ciba-Geigy, renamed Ciba in 1992

1993 Zeneca de-merged from ICI

1996 Ciba and Sandoz merge to form Novartis

1999 Astra and Zeneca merge

2000 Novartis agribusiness and Zeneca agrochemicals merge to form Syngenta

speaks for itself.

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Syngenta Research & Technology flow

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Syngenta product pipeline

Syngenta’s Biotechnology pipeline is comprised of the following Syngenta’s Biotechnology pipeline is comprised of the following Categories, which are expected to be on the market within the next decade, Categories, which are expected to be on the market within the next decade, pending regulatory approvals.pending regulatory approvals.

New applications of biotechnology - feed and crop processingNew applications of biotechnology - feed and crop processing Agronomic benefits in important crops - corn and cottonAgronomic benefits in important crops - corn and cotton Cereals - Disease resistant wheatCereals - Disease resistant wheat Whole Foods – StayRipe™ banana & Humanitarian Golden Rice Whole Foods – StayRipe™ banana & Humanitarian Golden Rice  Biopharma - Long-term potentialBiopharma - Long-term potential

Regarding Biopharma, Syngenta states:Regarding Biopharma, Syngenta states:  

"Biologicals represent the next generation of human pharmaceuticals. "Biologicals represent the next generation of human pharmaceuticals. But access to biologicals through traditional means can be limited by a But access to biologicals through traditional means can be limited by a number of factors, including the inability to make sufficient quantities number of factors, including the inability to make sufficient quantities and a high cost of production. and a high cost of production.

There is great potential for plant production to help overcome some of There is great potential for plant production to help overcome some of the factors that limit the availability of biologicals. the factors that limit the availability of biologicals.

Syngenta is building upon its traditions of scientific excellence and Syngenta is building upon its traditions of scientific excellence and responsible use of technology to deliver on the promise of responsible use of technology to deliver on the promise of biopharmaceuticals."biopharmaceuticals."

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Syngenta believes biopharmaceuticals hold great promise to Syngenta believes biopharmaceuticals hold great promise to address medical needs of the 21st century.address medical needs of the 21st century.

Syngenta’s biopharma business development unit has years of Syngenta’s biopharma business development unit has years of experience in plant biotechnology, bio-safety, pre-clinical and experience in plant biotechnology, bio-safety, pre-clinical and regulatory affairs to fully realize the biopharmaceutical potential.regulatory affairs to fully realize the biopharmaceutical potential.

““Syngenta’s roots in the pharmaceutical business could lead the Syngenta’s roots in the pharmaceutical business could lead the company in the direction of pharmacrops.”company in the direction of pharmacrops.”

David JonesDavid JonesHead of Business DevelopmentHead of Business Development

The Swiss company is investing $30 million of its more than $150 The Swiss company is investing $30 million of its more than $150 million annual biotech research-and-development budget in million annual biotech research-and-development budget in biopharmaceuticals.biopharmaceuticals.

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Bayer CropScience

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"We see plant biotechnology as a growing and emerging driver in the "We see plant biotechnology as a growing and emerging driver in the development of products to effectively meet demand for food, feed development of products to effectively meet demand for food, feed and fiber . . and all kinds of renewable resources as well. We are not and fiber . . and all kinds of renewable resources as well. We are not limiting ourselves to a particular segment. We have substantial capa-limiting ourselves to a particular segment. We have substantial capa-bilities and assets to bring to bear, and we intend to pursue this."bilities and assets to bring to bear, and we intend to pursue this."

Paul SchmidtPaul SchmidtHead of new business ventures Head of new business ventures Bayer CropScienceBayer CropScience

Bayer CropScienceBayer CropScience highlightsighlights

Bayer CropScience investing $880 million in 2004 in R&DBayer CropScience investing $880 million in 2004 in R&D

LibertyLink canola and corn were among earliest ag biotech products LibertyLink canola and corn were among earliest ag biotech products

Bayer CropScience plans to introduce canola with healthy oil content in Bayer CropScience plans to introduce canola with healthy oil content in 2007 or 2008. 2007 or 2008.

In the future, likely to tap parent Bayer AG's pharmaceutical expertise to In the future, likely to tap parent Bayer AG's pharmaceutical expertise to produce plant-based drugsproduce plant-based drugs

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Dow AgroSciences

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Dow AgroSciences focuses on the production of vaccines in Dow AgroSciences focuses on the production of vaccines in plant cells in vitro thus avoiding the confinement risk issues plant cells in vitro thus avoiding the confinement risk issues associated with making vaccines and other plant made associated with making vaccines and other plant made pharmaceuticals in whole plants or food crops. pharmaceuticals in whole plants or food crops.

Plant-cell-produced vaccines are a significant improvement Plant-cell-produced vaccines are a significant improvement over traditional vaccines since they do not contain any over traditional vaccines since they do not contain any components of animal origin.components of animal origin.