Slide 1 - KKY Partners LLC


Dec 5, 2012 (5 years and 4 months ago)



Table of Contents

The bio
manufacturing capacity squeeze

Emerging plant
based production technology

Pharmaceutical applications: Clinical and non

Industrial applications

Monoclonal antibodies (Mabs)

Advantages of plants as factories

pollination risk


Best Practices

APHIS Regulations


The bio
manufacturing capacity squeeze

Since the human genome was deciphered, biotech products have occu

pied a growing portion of the drug discovery pipeline.

BioLogic USA 2004

estimates that the biotech drug market today is worth over
$40bn. According to Syngenta,

biopharmaceuticals represent the fastest growing
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
billion in United States alone.

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

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

The pipeline:

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


Biotech drugs

Made from
Recombinant Therapeutic Proteins


particularly antibodies.

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

FDA has approved approx. 60 RTP
based pharmaceuticals.

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

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

limited in size

require high CAPEX

require 4 or 5 years’ lead
time to come on

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

New technology: Genetically engineered

cultivation row crops like corn and
tobacco to serve as “bio
reactors” to produce RTPs


Production bottleneck:

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

Fermentation systems have 3 drawbacks:

they are limited in size;

they require high capital expenditure (CAPEX);

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


Emerging plant
based production technology

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

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

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

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


Pharmaceutical applications: Clinical & non

The “first wave” of clinical applications includes edible vaccines,

antibiotics, anti
HIV drugs & anti
clotting agents, among others. Edible
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
toxin that causes "Traveler's Disease” and TGVE (Transmissible Gastro
Enteritis Virus). Other clinical products in the pipeline are Albumin, Aprotinin,
Trypsin, Lactoferrin and, significantly, monoclonal antibodies (details on next

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

Industrial applications

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

Source: Pioneer Hi
Bred & DuPont


Monoclonal antibodies (Mabs)

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

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

Estimated 190+ Mabs now in clinical trials; +/

350 Mabs in pre

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

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


Advantages of plants as factories

Plant cells are eukaryotic; they are capable of acting as efficient

natural bioreactors making complex proteins with therapeutic properties
equivalent to human proteins.

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

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

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

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


pollination risk

pollination can occur between pharmacrops and conventional

crops for human & animal consumption, which could lead to as
unmeasured health hazards.

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
characterize all pharmacrops. Therefore, the risk of cross
pollination remains a
top priority issue that must be very carefully managed.

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

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
USDA responded by issuing new safety regulations:

Inspecting test plots 5 times per growing season instead of once

Greater separation distances between conventional crops and pharmacrops

Mandatory separate storage, planting & harvesting equipment


APHIS Best Practices

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

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

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




[Docket No. 03
1] March 10, 2003
Federal Register Vol. 68, No 46

Governs field testing
of plants engineered to produce pharmaceutical and
industrial compounds. APHIS authorized over 1000 field tests in 2002, of
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)

[Docket No. 03
1] August 6 2003
Federal Register Vol. 68, No 151

Compounds for industrial use:

Interim regulation till 12/31/04,
mandates prior government permit

for introduction of plants genetically
engineered to encode industrial compounds. Only 10 applications were
submitted to introduce plants producing industrial compounds in the 10
year period 1993
2003. 5 permit applications were submitted in the 6
months between Aug 2003 & Jan 2004.

[Docket No. 03
2] January 23, 2004
Federal Register Vol. 69, No 15

Environmental Impact Statement

(EIS) will address new trends including the use
of genetically engineered plants to produce pharmaceutical and industrial compounds.


The approval process for the introduction of GM plants for pharma

or industrial uses takes 3+ months.

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

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

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

APHIS Biotechnology

site map

Current Status of APHIS approvals

APHIS permitting process


Market makers

Research conducted by Freedonia, Theta and Drug & Market
Development Corp. estimate that ~60 private companies

and ~60 research institutes worldwide

are involved in biopharming R&D
with a strong product development pipeline, active field trials, advanced
regulatory approvals and affiliations to leading grain or seed companies.

These are the some of the high profile players.

BASF Plant Science



Pioneer Hi

Bayer CropScience

Dow AgroSciences

Exelixis Plant Sciences

Ventria Bioscience








Iowa State U

DOE Genomics:GTL

Mendel Biotechnology

Icon Genetics

Large Scale Biology Corp





Meristem was founded in 1997 to implement the Molecular Pharming®

plant genetics program initiated in 1992 by LIMAGRAIN, the world’s 2

largest seed company. Meristem has contractual access to Limagrain’s
infrastructure, in
field production know
how, patented germplasm, and plant male
sterility anti
pollen dispersal technology. As well, via R&D in

and out
agreements there are regular exchanges of scientific information with Limagrain.

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
are located in
, in the south central region of France. The
company has raised Euro 40+ million from life science investors led by Banexi
Ventures Partners.

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

Meristem’s Molecular Pharming® technology can produce recombinant proteins
from the gene up to production of several tons of purified active substances. The
platform offers several comparative advantages for the production of complex
therapeutic proteins
including antibodies

in terms of biological safety, volume,
cost, speed of production and scale


Meristem’s most advanced compound is gastric lipase, used in the

treatment of Exocrine Pancreatitis Insufficiency, a digestive disorder

afflicting cystic fibrosis patients. Other compounds in the pipeline are human

serum albumin (HSA), lactoferrin, collagen, monoclonal antibodies and

recombinant allergen from dust mites.

Meristem holds various license and/or research agreements with:

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

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

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

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

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

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


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

For 3

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

Meristem has the world's 1st kilogram
scale pilot facility for the extrac

tion and purification of pharmaceutical grade plant
derived recombinant

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

lipase per year.

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


Meristem successfully produced milligram quantities of complete and

conform monoclonal antibodies in tobacco. It forecasts manufacturing
monoclonal antibodies at a cost similar to other recombinant proteins

in its development pipeline, which could reduce cost by as much as 5

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 antibodies share almost entirely the same protein chain configuration.

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
Chile. By alternating the growing seasons between France, Spain, Chile and the
USA, multiple production cycles are possible each year.


Verdia, Inc.


Verdia was established in 1999. In July 2004 DuPont acquired Verdia

from Maxygen (Nasdaq:
) for $64 MM.

Verdia’s MolecularBreeding™ technology is designed to
direct molecular evolution

to optimize input traits (disease, herbicide & pest resistance) and output traits
(nutritional value) through high throughput (HTP) assays that selectively
“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
MolecularBreeding™ technology will allow it to accelerate its gene research
targets by as much as 3 years.

Verdia’s focus is on developing novel input traits for the major row crops

soybean & cotton

as genetic alternatives to the $28 billion crop protection
chemical market. Three pipeline projects

biofuels, specialty chemicals &
enabling technologies

appear oriented toward industrial compounds.

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 gene material depends on market opportunity, commercial potential,
technical feasibility and the competitive landscape.

Once HTP assays have predicted which genetic material most efficiently codes for
desired traits, single or multiple genes are recombined in 2 discrete “
” steps

“DNA Reshuffling” and “MaxyScan™”.


Traits expressed by reshuffled genes are validated in

using model plants like tobacco or
Arabidopsis Thaliana
, a weed

intensely studied by researchers due to its rapid growth and compact


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

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

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

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 issued foreign patents and approximately 200 pending U.S. and foreign




Verenium (Nasdaq:
) emerged from the merger between

Diversa and Celunol.


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

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

Verenium’s process has 2 advantages by comparison to lab

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

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


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

Each GigaMatrix

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

GigaMatrix is capable of screening
one billion clones per day, permits
rapid screening of genes and gene
pathways, thus maximizing the

novel enzyme &
small molecule drug discovery.





is a private company focused on developing recombinant

therapeutic proteins and monoclonal antibodies by leveraging the

natural characteristics of the small green aquatic plant,

Biolex has a proprietary genetic engineering and protein recovery LEX System™
that can escalate a protein from amino acid sequence to purified product for
clinical trials and commercial supply.

Biolex is funded by a syndicate of life science venture firms and strategic
investors including Johnson & Johnson and Dow.

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

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

Plant replication without pollen or seeds

Fast growth rate, with biomass doubling every 36 hours

High protein content resulting in high expression levels

Secretes target protein into an easily purified medium

Contrary to filed crops, production is in a contained & controlled facility

Previous point permits high conformance to regulatory requirements

Scale up is quick and predictable


The natural characteristics of

coupled with the contained

LEX System™ avoids most of the environmental risks associated

with plant
manufactured pharmaceuticals.

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

In 2004 Biolex
acquired Epicyte Pharmaceuticals

which specializes in the
discovery and development of human monoclonal antibodies, having successfully
expressed (in corn) an antibody for protection against herpes simplex virus

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

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

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


Exelixis Plant Sciences


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

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

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

After acquiring Agritope Inc. in 2000, Exelixis formed
Exelixis Plant

to expand its access to plant model system technologies
and product development.

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


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

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

Exelixis’ proprietary gene discovery technology has been developed

LLC, a 50
50 joint venture between Exelixis and
Bayer CropScience.

The gene discovery technology uses a positive genetic trait
identification methodology known as “activation tagging” (ACTTAG™)
to identify gain
function and loss

mutations and to
permit up
regulation or over
expression as vehicles for plant trait


Large Scale

Biology Corporation



Large Scale Biology Corporation
(LSBC) produces biopharmaceuticals

and other commercial proteins from plants using its GENEWARE®

technology platform that comprises industrial
scale processes for

the extraction and purification of proteins, peptides and other

biochemicals from plant biomass, mainly tobacco.

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

The company has a 27,000 square foot

production facility in Owensboro, Kentucky,
used to produce commercial quantities of recombinant crops and a range of
therapeutics including peptides, enzymes and vaccines.

LSBC has strong intellectual property protection through 52 issued US patents and
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
individualized therapeutic vaccines to treat patients with B
cell non
lymphoma (NHL).


LSBC is aiming at developing personalized medicine tailored to the

specific needs of patient populations or even individual patients.

LSBC believes this approach will become a key driving force in 21

century medicine and pharmaceutical development.

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

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

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

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


Ventria Bioscience


Ventria Bioscience, headquartered in Sacramento, California, has

created a rich product pipeline in human nutrition, human therapeutics

and animal health, through internal R&D and collaborations with world

renowned biotech and industry leaders.

The company is led by renowned
Board of Directors
, an experienced
, a rich
scientific network

and leading
edge scientists who, prior to joining
Ventria, had accumulated over 120 years of biotech experience, registered 145
U.S. and foreign
, and published over 600
scientific papers

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

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

treatments on a global scale.

ExpressTec production includes

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


Economically advantaged expression capability (e.g. 10g/kg of brown

Proven scalability for large volumes of recombinant proteins/peptides with
minimal capital investment compared with other systems

Free of infectious or toxic contaminants

pollinating crops provide a safe and closed production system

Efficient supply management since the protein/peptide can be stored in its

lowest cost form for multiple years

Utilizes a proven production and processing infrastructure

ExpressTec uses self
pollinating crops

(rice and barley) as the

production host for these products, bypassing many of the

technological constraints inherent in other protein production


The key benefits are:

ExpressTec is versatile, expressing the following range of molecules:

Large molecules (larger than 50 kD)

Small molecules (less than 10 kD)

Multiple sub
unit molecules (e.g. fibrinogen)

Structural/functional proteins or enzymes

Products resulting from metabolic engineering




Headquartered in Basel, Switzerland, Syngenta is a world leader in

agribusiness crop protection, ranking 3rd in the commercial seeds

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
Swiss stock exchange (SYNN) and in New York (

Since May 2004 Syngenta is the process of acquiring Advanta, the 5th largest
agricultural seed company in the world.


is a

Dutch company owned by
AstraZeneca (UK) and Royal Cosun (Netherlands). Both the E.U. and the US
Department of Justice have approved the deal, structured as follows:

Syngenta will acquire all the shares of Advanta BV

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

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
$ 1.5+ billion under management

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

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%
and broaden Syngenta’s germplasm base and enhance its platform for
biotechnology products.


The Syngenta genealogy…


Geigy founded


Sandoz founded


Ciba established

Imperial Chemical Industries (ICI) formed through merger


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


Zeneca de
merged from ICI


Ciba and Sandoz merge to form Novartis


Astra and Zeneca merge

Novartis agribusiness and Zeneca agrochemicals merge to form

speaks for itself.


Syngenta Research & Technology flow


Syngenta product pipeline

Syngenta’s Biotechnology pipeline is comprised of the following

Categories, which are expected to be on the market within the next decade,
pending regulatory approvals.

New applications of biotechnology

feed and crop processing

Agronomic benefits in important crops

corn and cotton


Disease resistant wheat

Whole Foods

StayRipe™ banana & Humanitarian Golden Rice


term potential

Regarding Biopharma, Syngenta states:

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

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

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


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

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

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

David Jones

Head of Business Development

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


Bayer CropScience


"We see plant biotechnology as a growing and emerging driver in the
development of products to effectively meet demand for food, feed

and fiber . . and all kinds of renewable resources as well. We are not

limiting ourselves to a particular segment. We have substantial capa

bilities and assets to bring to bear, and we intend to pursue this."

Paul Schmidt

Head of new business ventures

Bayer CropScience

Bayer CropScience


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

LibertyLink canola and corn were among earliest ag biotech products

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

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


Dow AgroSciences



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

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