Innovation in Action. Passion to innovate. Global Conference on Sustainable Beef. Power to change. Science for a better life ///////////

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Global Conference on Sustainable Beef Innovation in Action Passion to innovate Power to change /////////// Dr Zsolt Szeidemann, Beef Species Team 11 Oct 2018 Science for a better life

150 years of innovation Bayer Animal Health: our shared responsibility drives our actions Bayer Science for Better Life people-food-animals Animal Health 1,5B sales 3000 employees 100+ products CAP&FAP Beef Group Parasiticides & BRD 2

Innovation #1 Customized Parasite Control ///////////

External parasites Why bother? Economic (in USD), health and well-being impact Direct health damage + vector borne diseases USA (Talley 2016) Horn fly 1,360M Stable fly 672M Horse fly 296M Face fly 191M Ticks 162 M Mosquitos 78M Lice 56M Brazil (Grisi et al 2014) GI parasites 7,100M Ticks 3,240M Horn fly 2,558M Cattle grub 383M Myasis 336M Stable fly 335M Mexico (Rodriguez-Vivas et al 2016) Ticks 573M GI parasites 445M Horn fly 231M Liver fluke 130M Coccidia 23M Stable fly 6 M Australia (AFI 2015) Ticks 156M (N) Buffalo fly 99M (N) Ephemeral fever 60M (N) Intestinal parasites 82M (S) Theileria 18M (S) Pink eye 11M (S) + animal wellbeing aspects 4

Challenges to parasite control Resistance not IF but WHEN? Diminishing governmental support Environmental safety and pesticide handling Rising regulatory requirements and development costs Climate change and trade facilitating spread of parasites Diverse customer preferences by regions Rampant resistance to parasiticides European cattle breeds taking over more resilient Asian breeds Limited education Immature alternative parasite control technologies Generic market Constant battle for the cattle industry Date of introduction (R. microplus) 1 st resistance arzenicals 1893 1936 (AUS) DDT 1846 1953 (AUS) organophosphates 1944 1963 (AUS) amidines 1975 1978 (AUS) pyrethroids 1977 1981 (AUS) macrocyclic lactones 1981 2001 (BRA) fipronil 2008 2012 (MX) 5

Holistic approach required Collaboration with all stakeholders Environmental aspects Product/portfolio development Customized Parasite Control Safety Pasture management Education & training Resistance monitoring 6

Product development Tradition, combined expertise and sustained innovation with Bayer Crop Science and Pharma Registration (2 years) 1 Customer need Development (3-8 years) 60M development compound 5 development candidates Broad spectrum Resistance-breaking Convenience Cattle ecto & endoparasiticides Discovery (2-4 years) 15-20M BCS & BPH 10 POC 200-2,000 synthetized compounds 1M screened compounds new compound class multiple projects progress 7

Broad portfolio for rotation Example: Defense Point (US) 8

Resistance monitoring and diagnostics Example: on farm diagnostic (MX) Triple Boophilus resistance 1 1983 Tick Control Rules #1 use the right active ingredient OP s SP s 1994-1995 2001-2008 #2 follow product label #3 rotate #4 vaccinate #5 strategic control #6 other management tools amitraz #7 justified macrocyclic lactone use Digital fly counting (in the works) 9 1 SENASICA/SAGARPA

Pasture management Example: weed management on pastures and grazeland (US) The hardest thing for most livestock producers to realize is that we are not in the cattle business. We are in the grass business. We are in effect, grass farmers. Allan Nation (editor, The Stockman Grass Farmer) 10 1 AgriWebb (https://www.youtube.com/watch?v=vzyyvs7ckqw)

Innovation #2 Zelnate ///////////

The challenge Complex disease stress + pathogens M haemolytica, P multocida, H. somnus, Mycoplasma spp, IBR, BVDV, PI3, BRSV Growing intensification 30% more beef 30% less cattle 1 feedlot mortality increased from 10.3 to 16.0 per 1000 cattle between 1994-2011 2 Consumer pressure on antibiotic use 59,3% of feedlot cattle in US receives AB on arrival 3 12 1 Capper: The environmental impact of beef production in the United States: 1977 compared with 2007 JASc Vol 89 Issue 12 2011 2 2014 Maday, The ongoing battle with BRD, Bovine Veterinarian (September) 30-33 3 NAHMS 2011

Doing the same thing over and over again and expecting different results? Focus on the host`s immune status rather on the bugs ENVIRONMENT HOST MANAGEMENT Viruses Vaccines Antibiotics Immunostimulants PATHOGEN Bacteria 13

Novel Mode of Action Stimulation of innate immunity 1 STINGactivation effects production of type 1 interferon anti-inflammatory activities antiviral and antibacterial activities counters Mannheimia haemolytica LPS effects prevents extensive lung inflammation, fibrosis, aids in combatting Mannheimia haemolytica 14 1 Ilg, Investigations on the molecular mode of action of the novel immunostimulator Zelnate: activation of the cgas-sting pathway in mammalian cells, Molecular Immunology, 90 (2017) 182-189

First licensed immunostimulant with BRD indication Extract from the USDA label Indication Aid in the treatment of Bovine Respiratory Disease due to Mannheimia haemolytica in cattle 4 months of age or older, when administered at the time of, or within 24 hours after, a perceived stressful event Dosage and administration 2 ml IM single dose Withdrawal time 21 days Zelnate is based on technology developed by Juvaris BioTherapeutics and is patent protected. Animal health applications are being exclusively developed by Bayer Animal Health and are the subject of Bayer patent applications. 15

Challenge studies demonstrated high efficacy 1 Zelnate as a stand-alone therapy significantly reduces lung lesion scores associated with BRD when administered in the face of disease challenge significantly reduces the risk of mortality when administered in the face of clinical BRD 16 1 USDA label

confidence interval of delta within -10% Field study suggests potential to replace antibiotics on arrivals 1 In defined cattle population and in metaphylactic setting Parameter P-value BRD morbidity (%) 7.65 13.84 non-inferior* Time to treatment (days) 28.1 22.6 <0.0001 BRD repulls (%) 17.90 11.10 0.5929 BRD chronicity (%) 27.90 29.10 0.9942 Overall BRD mortality (%) 0.44 0.50 0.7643 BRD case-fatality (%) 3.95 2.99 0.7287 ADG (lbs) 2.96 2.91 0.6759 DMI (lbs) 12.96 12.81 0.3768 Feed:Gain 4.50 4.55 0.7302 No statistical differences between treatment groups across all clinical and economic parameters. In this study, Zelnate was shown to be a viable nonantibiotic option for metaphylaxis in medium-risk feedlot cattle. 17 1 Nickell et al. A comparison of clinical and economic outcomes when metaphylactically administering either a novel DNA immunostimulant or tilmicosin to beef calves at medium high risk of developing bovine respiratory disease in the feedlot; RUAA, Den Hague, 2016

Our livestock. Our responsibility. Our future. delivering science based products and services introducing smart digital technologies enabling collective intelligence of all stakeholders 18