Innovation in Agricultural R&D:
Targets, Priorities and Delivery
CGIAR ADE-PSC Workshop
November 11th 2009
Dr Mike Bushell
Principal Scientific Advisor
Syngenta
Brief and themes
● The Research Process in Syngenta R&D
- Crop Protection Chemicals
- New crop varieties
● Organising for success
- How to agree research targets and priorities
● Innovation Culture
- Open Innovation
- Importance of Partnerships
- Research vs Development mindset
2
Research Target Profile
● Customer Need
● At the outset, could be pretty simple and high level...
- E.g. Broad spectrum cereal fungicide
● Knowledge of essential and desirable characteristics
● Knowledge of current market ($$size by country – key crops
and diseases, current offers, competition)
● View of market trends and changes 10years ahead
-
3
Market size for new active ingredient >>$100m
Time to market, 10+ years; cost $250m + capital
Cost depends on complexity, crop, country, pest spectrum
New formulation project are a different ballpark...time and cost
Disease, Insect, Weed Control Research Targets
Cereals
Fruit &Veg
Field crops
Non-selective
Corn selective
Cereals selective
Soya Bean selective
Rice selective
Sucking pests
Nematodes
Soil pests
Lepidoptera
4
Crop protection compounds: the long road to market
30
Develop
100’000
compounds
1-2
Evaluate
Profile
5000
compounds
Discover
Time
5
Lead Generation
● Agreed target profile will have additional critical success factors
- E.g. Fish safety
● How to find best starting points?
- Screening data searches (in house databases)
- Literature
• Competitor Patents
• Natural Product inspired
- Rational Design, e.g. based on a biochemical hypothesis
● Find or make a compound of significant interest – activity on target
pests, interesting mode of action, space for innovation (IP)
- Chemistry, Biology, Biosciences
- Typically mg to gram amounts
6
7
In vivo screening
8
Crop protection compounds: a long road to market
Research
Lead Optimisation
Lead Generation
Develop
100’000
compounds
1-2
Evaluate
30
Profile
Discover
Potential for collaborations at
every stage of the process
5000
compounds
Time
9
Optimisation Project
● Multidisciplinary project teams – large resources
● Portfolio process operates
-
Dedicated portfolio leader and planners
Regular review, annual portfolio review
Priority setting at the sub portfolio level
Flexible management of resources
● Strong linkage to the development and commercial functions
in centre and in key regions (APAC, NAFTA etc)
● Field trial programme on best analogues
● Increasing clarity on properties of the series and full profile
of leading candidates – activity, tox, ecotox
● Commercial potential
10
Crop protection compounds: a long road to market
Research
Develop
100’000
compounds
1-2
Development
Evaluate
30
Profile
Discover
5000
compounds
Stage
Gate
Process
Time
11
Candidate Selection and Development Decision
● What do I have to know to progress into development?
• Does it work?
• Can we make it?
• Is it ours?
• Is it safe?
• Can we sell it?
● Simple questions, but with multiple levels of details
● Performance in field trials, competitive position, manufacturing routes
and ballpark costs, complete review of all IP on candidate, processes
and formulations, biochemical mode of action, mammalian and
environmental safety profile, registration risks, and more....
● Full business case, costs, timelines, assumptions, financial measures
12
Development stage
● Development needs a very different mindset to Research
● Always change Project Leader by this stage
- Engineered handover – full time PL
● Complexity requires planning at a high level, 5-7 years to
sales
• Specialist functions own and deliver their own part
• Financial case depends on speed to market
- Critical path analyses
● Networks that the PL needs are different to mobilise
resources – downstream, techno-commercial, regional and
in key national countries
13
The Innovation Process
Numerous, partially
developed ideas
Portfolio Management
External
Technology
Decision
BLUE SKY
OPPORTUNITY
IDENTIFICATION
Stage 1
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OPTIMISATION
Stage 2
Handover
DEVELOPMENT
Stage 3
External Innovation is Critical for Success
“External Collaborations plays
a key role in nearly 50% of
P&Gs products… Our vision is
simple. We want P&G to be
known as the company that
collaborates – inside and out –
better than any other company
in the world”
A.G. Lafley, CEO OF P&G
15
“Not all smart people
work for you”
Bill Joy
Sun Microsystems
“We intend to make our internal
capability even more effective by
tapping into the best scientific
capability outside of our walls
wherever it exists.”
Jeff Kindler, Chairman and CEO
Pfizer 2007
Henry Chesbrough, Open Innovation 2003
16
Benefits of collaborations
● Soft benefits
- Window on external technology
• Technology foresight
- Opportunity for professional development of our science leaders
• interaction with top academics and institutions
• involvement with frontier research areas
• breadth and interest in science
• broader horizons – increased Innovation potential
- Relationship building
• recruitment
• company image
• consultancy and advocacy
- Contribution to building the Global knowledge economy
• Encouraging science in our local home bases
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Benefits of Collaborations (2)
● Harder business benefits
- Access to technology quickly without building internal capability
• speed and flexibility
• cost – revenue and/or capital
• quality
• evaluate new technologies before bringing in house
- Technology acquisition for product development
• new lead areas for Crop Protection
• new traits for GM plants or traditional breeding
- Product support work
• agronomy, weed, disease and pest resistance studies
• part of regulatory submission or technical marketing story
18
Collaborations come in all sizes
● Formulation Robot - the culmination of a 5 year project to design and
build this unique facility
● Bosch – IP sharing for mutual advantage
19
University Innovation Centres
- Innovation Centres
• Microbiology and natural products (HBERC, Wuhan)
• Sensors (Manchester)
• Polymer Chemistry (Warwick)
• Synthetic Chemistry (SIOC)
• Systems Biology (Imperial)
• Sugar Cane (Queensland)
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Biofuels: improving efficiency
Sugar Cane
● Soil conservation (minimal till, less
compression)
● Efficiency (improved mechanization,
reduce costs, integrated SC)
● Reduces CO2
● Launch 2011
Corn amylase
● Breakthrough technology
● Third successful trial
● 8-15¢/gallon benefit
● Awaiting USDA approval
21
Increasingly complex farmer needs beyond single ag inputs
Old
Must-have
Customer needs
● Yield potential
New
Importance
low
(seeds breeding)
● Biotic stress control
(weeds, insects, diseases)
high
Ag input technology:
single seeds, chemicals
benefits
Differentiators
● Abiotic stress control
(eg heat, drought)
● Use efficiency
(eg nitrogen use)
● Farm profitability
(eg labor, cost flexibility)
● Convenience, simplicity
“Farmer of the future”:
focus on profitable yield
realization; multiple
parameters
(eg no-till)
Future
needs
● Sustainability, safety
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(eg carbon, residues)
● Quality
(eg protein, healthy oils)
Value chain/consumer:
increasing influence on
supply chain, farmers
1. Corn: leading drought tolerance technology, 2011 launch
● Productivity & cost advantages
- ~10% more yield
- ~50% less water
● Stabilize yields
● Reduce moisture needs on
existing cropland
- Less yield loss in dry years
- Less irrigation in normal years
● Increase productivity from
marginal cropland
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Pending regulatory approvals, not meant to be an offer for sale.
2. Moddus: water efficiency increases yield and quality
10% less water and 25% more yield compared to competition (not the control!)
Source: Prof. S. Schubert,
University of Giessen
Germany 2004
Australia (2006): Avg. 13% increased yields in stressed environments in irrigated areas; 7% in rainfed areas
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Source: Charts taken from US Sales Kit pack for Moddus and Germany Research Report
3. Invinsa: water and heat stress management
Invinsa
Control
Invinsa
Invinsa V12
UTC
Oil
Untreated Control
Medium N
Invinsa
Low N
Improved N Use Efficiency
Medium N
Low N
Untreated Control
Kansas State University-2007
25
Customer benefit : better germination, stronger stand
establishment
Thiram
(Check)
Fungicide seed treatment controlling of soil-borne diseases that affect the
germinating seedling
26
Crop enhancement : chemicals and genetics working together
Evidence from the field
Growers notice :
• Healthier, more vigorous plants
without pest pressure
• Translates into higher yields
Evidence from the lab
• Healthier, more vigorous maize
seedlings treated with
Thiamethoxam (Cruiser®)
• No pests, controlled environment,
sterile soil....
Untreated
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Cruiser® treated
Agricultural technology : for a sustainable future
● Increasing yield
-


high yielding seeds
stress tolerance e.g. drought
crop enhancement
seed enhancement (priming/pelleting etc)
fertilisers
mechanisation incl. irrigation, protected crops


● Protecting yield
-
weed and pest control agents
seed treatment

● Improving yield quality
-

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= customer benefit delivered in or on the seed

oil composition of oilseeds
taste and nutrition of fruit/vegetables
baking/brewing quality of cereals
Biofuel-enabled crops



Our core, moving toward Integrated Crop strategies (ICS)
Takes yields
to a new level
Protects
yield potential
Reduces
loss
Sets yield
potential
Crop
Care
Pest
Control
Seeds
Basic
growing
conditions*
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* Soil fertility, micro-climate, water availability
Crop
Enhancement
Plant
Potential
Flavour and productivity in fruit and vegetables
Health
attributes
Disease / virus
resistance
Flavor
Consumer
traits
Yield
Color
Plant habit
Texture
Stress tolerance
Firmness
Long
shelf life
Post-harvest traits
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Grower
traits
Delivering flavour to the customer
Understand the
consumer
Understand the
metabolites
Sucrose
Understand the
genetics
Raffinose
Trehalose
Galactose
Maltose
Arabinose
Glucose
Starch
Threonate
G6P
Mannitol
Ribulose-5P
F6P
Cysteine
Ascorbate
Fructose
Sorbitol
O-acetylserine
Inositol
Leucine
Glycine
3-PGA
Serine
Glycerate
Glycerol
Glycerol-3P
Tryptophan
Valine
+
PEP
+
Shikimate
Phenylalanine
Isoleucine
Asparagine
alanine
Alanine
Aspartate
Pyruvate
OAA
Citrate
Glutamine
Pyroglutamate
Isocitrate
Methionine
Homoserine
Tyrosine
Quinate
Malate
-ketoglutarate
Glutamate
GABA
Threonine
Fumarate
Proline
Arginine
Putrescine
Succinate
Ornithine
Consumer Science
Metabolomics
Genomics
Correlations that associate QTLs/genes with consumer-desirable traits
Confidence in product attractiveness from the start
31
Sensory analysis: compare varieties across different attributes
Var #3
Var #2
Var #1
Control
What causes the difference in sweetness, is it just sugar?
32
Flavour dissection sets targets for trait discovery
Genetically
mapped
populations
Metabolite fingerprints
highlight effects between
genetic regions
Sucrose
QTL or candidate genes
discovered
Raffinose
Trehalose
Galactose
Maltose
Arabinose
Glucose
Starch
Threonate
G6P
Mannitol
Ribulose-5P
F6P
Cysteine
Ascorbate
Fructose
Sorbitol
O-acetylserine
Inositol
Leucine
Glycine
3-PGA
Serine
Glycerate
Glycerol
Glycerol-3P
Tryptophan
Valine
PEP
Shikimate
Phenylalanine
Isoleucine
Asparagine
alanine
Alanine
Aspartate
Pyruvate
OAA
Tyrosine
Quinate
Citrate
Glutamine
Pyroglutamate
Isocitrate
Methionine
Homoserine
Malate
-ketoglutarate
Glutamate
GABA
Threonine
Fumarate
Proline
Arginine
Putrescine
Succinate
Ornithine
Metabolite QTL*
Sucrose
Raffinose
Trehalose
Galactose
Maltose
Arabinose
Glucose
Starch
Threonate
G6P
Mannitol
Ribulose-5P
F6P
Cysteine
Ascorbate
Fructose
Sorbitol
O-acetylserine
Inositol
Leucine
Glycine
3-PGA
Serine
Glycerate
Glycerol
Glycerol-3P
Tryptophan
Valine
PEP
Shikimate
Phenylalanine
Isoleucine
Asparagine
alanine
Aspartate
Methionine
Homoserine
Alanine
Pyruvate
OAA
Tyrosine
Quinate
Citrate
Glutamine
Pyroglutamate
Isocitrate
Malate
-ketoglutarate
Glutamate
GABA
Threonine
Fumarate
Proline
Arginine
Putrescine
Succinate
Ornithine
33
Targeted assembly
possible with
genome wide
markers
Evolving technology = growing understanding = more potential
Past
Current
Future
• Rice / Arabidopsis
Genome
• Multiple Plant Genomes
• Expression Profiling
• Public Data sets
• Genomes of target crops
• Literature Mining
• QTL / Genetic Maps
• Metabolite Profiling
• Public Collaborations
• Biochemical/Genetic Pathways
• Next-Gen Sequencing; HD Genotyping
• Reverse Genetics
• Forward Genetics
• Genome-wide analysis
• Managed stress environments
• Environments x Chemicals x Genetics
• Precision phenotyping
• Improved data integration and validation
One Dimensional
Analysis
• By single data type
• Single crop/single trait
application
• Monogenic traits
• Markers for selection
• Network Analysis and Data Modeling
Two Dimensional Analysis
• Epigenetics
• Integrating and overlapping
multiple data types
Multi Dimensional Analysis
• Cross-crop data mining
• Understanding mechanisms
• Native traits and GM traits
synergy
• Exploiting diversity
• Multiple genes/QTLs
34
• Systems approaches
Integrating technologies for customer benefit
Innovative crop protection
chemistry and Seed Care
Biotechnology
expertise
35
Precision breeding
and plant genomics
Collaborations are Important and Fun!
● There is a lot of exciting science out there
● We need to be internally focussed on delivery, but
outward looking to seek useful opportunities
● Partnering with leading academic centres and companies
and in-licensing of novel compounds and innovative
products and technologies
● Partnerships that complement our in-house capabilities
and play a key role in strengthening our portfolio
Building Value through Partnerships
Driving Growth through Innovation
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Our company
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