THE FUTURE OF BIOCONTROLS FOR WELCOME, BY TOON MUSSCHOOT - HEAD CORPORATE AFFAIRS BENELUX

TUESDAY 29 NOVEMBER 2016 GHENT INNOVATION CENTER OPENING SPEECH MR. WILLY BORSUS, FEDERAL MINISTER OF AGRICULTURE

TUESDAY 29 NOVEMBER 2016 SYNGENTA GHENT INNOVATION CENTER SYNGENTA BIOCONTROL STRATEGY JEAN-PHILIPPE ALBERT - HEAD OF NEW TECHNOLOGY

TUESDAY 29 NOVEMBER 2016 SYNGENTA GHENT INNOVATION CENTER Helping small and large meet the challenges of global food security

OUR AMBITION 8M large-scale farms >100 Ha is to bring greater food security in an environmentally sustainable way

to an increasingly populous world

by creating a worldwide step-change

in productivity 450M smallholder farms ~2.0 Ha Demand for food is driven by population growth and rising calorie consumption

WORLD POPULATION WORLD DEMAND FOR GRAINS*

> 80% of growth in emerging markets bn tonnes 4 Developed +50% Emerging 3

2

1 Food Feed 0 1970 1990 2010 2030 2050 Source: FAO, Syngenta analysis * Cereals, and corn The growers’ world is becoming increasingly complex

New New Pests keep must not hurt pesticides I am nervous gaining bees or other must be safe of new resistance to beneficial for the technologies: my insects and are they safe? I don’t want I don’t trust environment. protection pollinators. big approaches. residues on companies. my food.

Increasing The value reguIations on chain and pesticides society are mean fewer having a crop protection greater products to influence on use. how I farm. Technology platforms across

Lawn and Garden

With the broadest portfolio in the industry Biocontrol products are based on naturally occurring compounds: minerals, microorganisms or plant extracts. They are used for biotic stress management in controlling fungal and bacterial diseases, arthropode pests, nematodes and weeds.

MINERALS MICROBIALS EXTRACTS SEMIO CHEMICALS Inorganic Microorganisms Plant, algae or Chemical signaling chemicals (virus, bacteria, fungi) other extracts molecules

CLASSIFICATION : EXTERNAL USE Syngenta has followed a selective licensing and acquisition approach to build its portfolio

PASTEURIA ACQUISITION BIOLOGICALS STRATEGY DSM PARTNERSHIP DEVGEN ACQUISITION

1993 2011 2012 2013 2014 2015

CLASSIFICATION : EXTERNAL USE Growth scenarios: by 2030 biocontrols could reach >7bn depending on industry ability to breakthrough performance barriers >7.0

Wave 3 – Breakthrough in performance • If standalone efficacy is similar to chemicals • ≥7% of total CP market $bn ex. industry

2 1.5 ~4.0 Wave 2 – Integration in crop protection 1 programs • If improved efficacy 0 2015 • 4-5% of total CP market

Macrobials <2.0 Botanicals Wave 1 – Driven by residue reduction Semiochemicals only Microbials • If no improvement to technology, efficacy 2030 remains inferior to chemicals • ~3% of total CP market Source: Dunham Trimmer − July 2014 + Syngenta - Assumption Global CP market CAGR 2015-2030 5%

CLASSIFICATION : EXTERNAL USE Performance will steadily improve driven by scientific advancements triggered by industry investments

• Investments of major R&D firms • Partnerships with experts in industrial scale • Increase in molecular biology expertise • Strain developent using protein engineering, GM, DNA sequencing • Bioinformatics & system biology • Applicatation of computer algorithms to build DNA databases • Advancement in product screening • Assay development, high throughput robots • Sponsorship of entrepreneurs/universities/institutes by governments and VC • e.g., Pasteuria Biosciences, many others

CLASSIFICATION : EXTERNAL USE Our strategy is to leverage strengths and collaborate with partners to bring high performing products to the market

Portfolio / R&D 1

Grow • Grow geography and label of our current biofungicides current products (short-mid term) • Pursue biology proofing in integrated programs

2 • Complement portfolio through licensing/ acquisition of technologies Unlock promising efficacies similar to chemicals promising technology • Leverage strengths in development, formulation, supply chain and (mid term) registration to unlock their full potential 3 Discover • Build a discovery platform with DSM breakthrough • Discover (and develop) game changing new product: technologies o for major crop segments (long term) o efficacy similar to chemicals and new MOA

CLASSIFICATION : EXTERNAL USE Syngenta biofungicide key brands

SAKALIA® Biofungicide

SPECIALTY • Plant extract from of Reynoutria sachalinensis (giant knotweed) • Fast acting plant defense activator • Helps deliver consistent disease control in high value fruits and vegetables against foliar VEGETABLES diseases • SAKALIA commercialized in Turkey; planned for EU 2018

TAEGRO™ Biofungicide

• Naturally occurring bacterium Bacillus subtilis var. amyloliquefaciens SPECIALTY • Broad spectrum, with activity against soil and foliar diseases • In integrated programs, can help reduce residues and secure marketable yields VEGETABLES • TAEGRO planned for EU in 2018, India, Mexico and South America in 2019

CLASSIFICATION : EXTERNAL USE Syngenta biofungicide key brands

AFLA-GUARD® Biofungicide CORN

• Non-toxigenic strain of Aspergillus flavus (NRRL 21882) • Significantly reducing aflatoxin levels (of up to 90%) PEANUTS • Helps manage complexities and risks associated with crop aflatoxin levels • AFLA-GUARD commercialized in North America; planned for EU, Australia and South America

TIMOREX® GOLD Biofungicide SPECIALTY

• Plant extract from Melaleuca alternifolia (Tea Tree)

• Acts by altering the membrane structures of pathogens VEGETABLES • Effective against a wide range of plant pathogens on various crops • TIMOREX GOLD commercialized by Syngenta in Chile, Mexico and Argentina

CLASSIFICATION : EXTERNAL USE

At the forefront of innovation, focused on delivering quality yield.

ADDRESSING GROWERS’ AND SOCIETY’S NEEDS WITH RNA-BASED BIOCONTROLS

GEERT PLAETINCK – SENIOR SCIENTIST GHENT INNOVATION CENTER

® SYNGENTA’S GHENT INNOVATION CENTER

ADD MOVIE BIOCONTROLS: AN EFFECTIVE SOLUTION TO MEET GROWERS’ NEEDS • Next-generation biocontrols are expected to offer significantly more activity compared to biological products of the past. • Will benefit from new, more custom-made formulations. • RNA-based biocontrols:  Act through a natural cell process (RNA interference, or RNAi).  Syngenta is a pioneer in the field with the development of a RNA biocontrol portfolio. RNA-BASED BIOCONTROLS: • A new paradigm in biocontrol :  Employing a new mode of action  Can be used like any other modern crop protection product  Compatible with current agricultural practices and chemical compounds  High product level efficacy  Highly selective product towards the targeted pest RNA-BASED BIOCONTROLS: MODE OF ACTION

A CELL OF THE PEST

nucleus

DNA

Blocked or degraded mRNA

cytoplasm

NO TARGET PROTEIN

The RNA-based biocontrol, The pest eats the biocontrol which is taken up into the pest’s The pest is controlled and the which is double-stranded cells. The RNAi process is triggered, which stops synthesis of plant matures to yield its crop. RNA, is sprayed onto the the essential protein in the target pest, controlling the pest Non-target insects are not plant. before it can cause too much damage to the crop. affected due to the precision of the RNA-based biocontrol. HIGH PRODUCT-LEVEL EFFICACY

ADD MOVIE GP Slide 6 UNPARALLELED PEST SELECTIVITY

CPB selective RNA-based biocontrol MLB selective RNA-based biocontrol RNA-based biocontrol against CPB and MLB COLORADO POTATO BEETLE RNA-BASED BIOCONTROL IS SELECTIVE

SPECIES COMMON NAME ORDER BIOLOGICAL ACTIVITY Spodoptera littoralis Cotton leafworm Lepidoptera No Plutella xylostella* Diamondback moth Lepidoptera No Bemisia tabaci* Silverleaf whitefly Hemiptera No Aonidiella aurantii Red scale Hemiptera No Aphis craccivora Cowpea aphid Hemiptera No Myzus persicae* Green peach aphid Hemiptera No Nilaparvata lugens* Brown plant hopper Hemiptera No Orius laevigatus Flower bug Hemiptera No Aphidius colemani Parasitic wasp Hymenoptera No Beneficials Apis mellifera* Honey bee Hymenoptera No Typhlodromus pyri Predatory mite Acarina No Tetranychus urticae Spider mite Trombidiformes No Frankliniella occidentalis Western flower thrip Thysanoptera No Callosobruchus maculatus Cowpea weevil Coleoptera No Diabrotica undecimpunctata* Spotted cucumber beetle Coleoptera No Diabrotica barberi Northern corn rootworm Coleoptera No Family: Diabrotica balteata Banded cucumber beetle Coleoptera No Chrysomelidae Diabrotica virgifera virgifera* Western corn rootworm Coleoptera No Phaedon cochleariae Mustard leaf beetle Coleoptera No Leptinotarsa decemlineata* Colorado potato beetle Coleoptera Yes

* Report sensitivity to eRNA RNA-BASED BIOCONTROL PROTECTS UNDER FIELD CONDITIONS EXPERIMENTAL FIELD TRIAL CONDITIONS • High incidence of Colorado potato beetle infestation • Populations of Colorado potato beetle that have developed resistance against classical pesticides

OBSERVATIONS AND RESULTS RNA-BASED BIOCONTROL • Treatment proved statistical equivalence to standard controls • Effective against adults and larvae • No impact on beneficial insects or predators of Colorado potato beetle

• No phytotoxicity UNTREATED • On planta stability for a relevant duration in time BROADENING THE TECHNOLOGY FOCUS TO MAJOR PESTS Soil Insects:

protection of 5 week old corn plants against Western Corn rootworm larvae, Diabrotica v. virgifera, through a drench applied RNA- based biocontrol BROADENING THE TECHNOLOGY FOCUS TO MAJOR PESTS… NEXT STEPS

EXPERTISE ACROSS R&D PLATFORMS

Bioactivity Delivery Mobility

Stability

EVALUATION OF 3rd PARTY TECHNOLOGIES FORMULATION TECHNOLOGY IMPROVES EFFICACY AND PERSISTENCE IN SOIL

30000

25000

) 2 20000

15000 area (mm area

Leaf 10000

5000

0 FORMULATION TECHNOLOGY IMPROVES STABILITY, DELIVERY AND PLANT PROTECTION Piercing and Sucking Insects: RNA-based biocontrol with formulation technology protects 2 weeks old soybean plants against damage by Southern Green Stink bug, Nezara viriluda SHARING DATA IN AN OPEN AND TRANSPARENT WAY

• Syngenta is committed to being transparent in how RNA-based biocontrols are developed and to periodically make our data available, to maximize the potential benefits for people, and the environment • We are sharing our early stage non-target insect screening data for our lead product as Open Data in order to engage in a new type of dialogue with scientists and researchers. • We partner with the Open Data Institute to publish our data to the best practice standards in the industry. • http://www4.syngenta.com/how-we-do-it/research-and-development RNA-BASED BIOCONTROLS ADDRESS SOCIETAL, GROWER AND ENVIRONMENTAL NEEDS

• RNAi is a natural process which regulates protein synthesis • The biocontrol is highly effective and biodegradable • The trigger can be made highly selective for a target protein in a target pest and therefore harmless for other non-target insects • Combining attributes which are important for effective insect control and • We will continue to perform trials and are committed to openly demonstrating the safety and efficacy of our biocontrol during the R&D process

COFFEE BREAK

Live demonstrations and posters on research into RNA-based biocontrols: - General information - Production methods - Colorado Potato Beetle - Corn Rootworm - Soy Stinkbug RNAi: A NATURAL PROCESS TO REGULATE PROTEIN LEVELS IN THE CELL

cytoplasm

nucleus

DNA

transcription

RNA

mRNA

translation

PROTEIN RNAi: A NATURAL PROCESS TO REGULATE PROTEIN LEVELS IN THE CELL

A CELL OF THE RNA-based biocontrol TARGET PEST cellular uptake

cytoplasm Dicer dsRNA cleavage

nucleus siRNAs 21-24mers DNA RISC complex activation

transcription RISC

RNA mRNA recognition

mRNA

mRNA degradation PROTEIN mRNA messenger RNA dsRNA double-stranded RNA siRNA small interfering RNA RISC RNA induced silencing complex UNPARALLELED PEST SELECTIVITY

TWO CLOSELY RELATED CHRYSOMELID BEETLES

• Colorado potato beetle (CPB) • Mustard leaf beetle (MLB)

TARGETING THE EXPRESSION OF A CONSERVED GENE PRESENT IN BOTH SPECIES

PRECISION DESIGN

• CPB selective RNA-based biocontrol • MLB selective RNA-based biocontrol • RNA-based biocontrol against CPB and MLB SYNGENTA AND DSM PARTNERSHIP DISCOVERY AND DEVELOPMENT OF BIOCONTROLS GAME CHANGER

MATTHIAS BRANDL, HEAD BIOLOGICIAL PRODUCTS DEVELOPMENT Contents

1 Strategic ambition for Syngenta/DSM partnership

2 Biocontrol market – current products

3 “Game changer” requirements

4 Complementary of partners and collaboration details

5 Status of joint partnership program

Syngenta/DSM partnership Syngenta and DSM partnership is a fully integrated key element of the Syngenta Biocontrols strategy

Portfolio / R&D 1 Grow • Grow geography and label of our current biofungicides current products • Pursue biology proofing in integrated programs (short-mid term)

2 Unlock • Complement portfolio through licensing/ acquisition of technologies promising promising efficacies similar to chemicals technology • Leverage strengths in development, formulation, supply chain and registration to unlock (mid term) their full potential 3 Discover Build a discovery platform with DSM breakthrough • Discover (and develop) game changing new products technologies o for major crop segments (long term) o efficacy similar to chemicals and new MOA.

Syngenta/DSM partnership

Syngenta/DSM partnership Present biocontrol products market situation is not exciting highlighting an urgent need for innovation

Organism Activity

Bacillus spec. Fungicidal Organism Activity Insecticidal Nematicidal Bacillus spec. Fungicidal Organism InsecticidalActivity Baculovirus Insecticidal Nematicidal Paecilomyces spec.Bacillus spec. Fungicidal Biological activities only Beauveria spec. Insecticidal Baculovirus InsecticidalInsecticidal AspergillusNematicidal spec. Burkholderia spec. Insecticidal Beauveria spec. Insecticidal Baculovirus Insecticidal Most biocontrols at average  40-50% control Chromobacterium spec. Insecticidal Burkholderia spec. Insecticidal Beauveria spec. Insecticidal Granulovirus Insecticidal Chromobacterium spec. Insecticidal are based on Burkholderia spec. Insecticidal Epicocum spec. Nematicidal Granulovirus Insecticidal Reliability questionable? Chromobacterium spec. Insecticidal Gliocladium spec. Fungicidal well-known Epicocum spec. Nematicidal Granulovirus Insecticidal Nucleopolyhedrovirus Insecticidal Gliocladium spec. Fungicidal Epicocum spec. Nematicidal microorganisms Metarhizium spec. Insecticidal Nucleopolyhedrovirus Insecticidal New MoA missing Gliocladium spec. Fungicidal Metarhizium spec. Insecticidal and have been Penicillium spec. Nucleopolyhedrovirus Fungicidal Insecticidal

Bacillus thuringiensisTrichoderma spec. Metarhizium spec. Fungicidal Insecticidal Penicillium spec. FungicidalTrichoderma spec. on the market High use rates & semi-optimal Trichoderma spec. Fungicidal … Penicillium spec. … Fungicidal for many years … Trichoderma spec. … Fungicidal formulations … …

Bacillus subtilis var. amlyloliquefaciens

Syngenta/DSM partnership Source: microorganism pictures - internet Need for biocontrols “game changer”, SYT and DSM partnership developing real innovation

 Higher biological activity  similar to chemicals

 Consistent and reliable control under diverse conditions

 Control of most relevant targets – solve unmet needs

 Discover and utilize new modes-of-actions

 Seamless fit in standard farm practices

 Scalable and used in sizable markets

Syngenta/DSM partnership Source: sign - internet Excellent complementary of key strengths of partners  ingredients for success

Market Excellence in market understanding/needs Relevance of In-vitro bioassays for primary testing Diverse microbial strain collection Strain selection test systems Excellence in microbiology/fermentation Sample preparation Profiling In vitro / in planta – GH for profiling Molecular biology/genetics and initial testing Development Field, toxicology, regulatory Bioinformatics/robotics

Formulation & application Up-down scaling manufacturing Optimization Fermentation Scale-up Manufacturing Leadership in Ag markets Up-down scaling manufacturing Go to market Down stream processing Global footprint marketing/sales

Syngenta/DSM partnership Complementing strengths: an impressive landscape of capabilities

Clinton Jealott’s Hill US UK Ghent Belgium Stanton SYNGENTA US Enkhuizen Netherlands

Key research and Slater Bad Salzuflen Greensboro,US Germany development US Stein centers across the Switzerland Beijing China world… Woodland US Unrivalled global Research Breadth. Triangle Park General Santos US Philippines Gilroy Sarrians US Saint Sauveur France France TakFah Thailand Goa Uberlândia India Brazil Hyderabad India Syngenta/DSM partnership The DSM “network of excellence”

DSM Biotechnology Center Delft, Netherlands

DNP/Microbia Boston, USA

DSM Biotechnology Center Shanghai, China

DNP/Martek Columbia, USA

DNP/DFS DNP DNP Kaiseraugst/Sisseln, Switzerland Belvedere, USA Grenzach, Germany

Syngenta/DSM partnership DNP: DSM Nutritional Products A look at Syngenta and DSM core capabilities enabling creation of new biocontrol discovery platforms

Syngenta/DSM partnership A look at Syngenta and DSM core capabilities enabling creation of new biocontrol discovery platforms

Syngenta/DSM partnership Syngenta/DSM complementing activities in action

Delft/NL Stein/CH

• In vivo/in planta testing • Validation/profiling • Strain collection • GH • Sample preparation • In vitro testing • Field development • Formulation & application • Process development • Regulatory • Manufacturing • Sales and New biocontrol Marketing products Syngenta/DSM partnership  One year Syngenta/DSM partnership: Excellent progress in all aspects

• Team constituted / work closely together Teamwork • Communication / interaction lively and fluid   Partnership • All program elements aligned and established

Discovery • Discovery work established and validated  screening • Routine work ongoing platform • Screening/testing work progressing 

Nov 2015 Nov 2016

Agreement Status signed today

Syngenta/DSM partnership

At the forefront of innovation, focused on delivering quality yield.

Q&A SESSION

PLENARY

® At the forefront of innovation, focused on delivering quality yield.

CLOSING REMARKS

MARITZA VAN ASSEN – DIRECTOR NEFYTO (Dutch Crop Protection Association)

® NETWORKING RECEPTION

Live demonstrations and posters on research into RNA-based biocontrols: - General information - Production methods - Colorado Potato Beetle - Corn Rootworm - Soy Stinkbug