Introduction of new fungicides for Septoria Leaf Blotch Control

Transcription

1 Introduction of new fungicides for Septoria Leaf Blotch Control Andy Leadbeater Head of Fungicide Technical R&D, Basel Switzerland EPP Workshop on azole fungicides and Septoria leaf blotch control, Rothamsted December 2010

2 Agriculture is innovation driven Percent of sales R&D investment as percent of sales by sector 2 2 Source: Financial Times, Phillips McDougall

3 Loss of active substances: Cereal fungicides example ? Strobilurin Strobilurin ther 18% 49% Triazole 33% ther 31% 8% Triazole 61% Strobilurin resistance continues to grow Triazoles significantly restricted by cut-off criteria Still fewer other alternatives available Strobilurins dominate, followed by triazoles Triazoles dominate Strobilurin resistance widespread Reduced Yields Loss of EU competitiveness Greater reliance on grain imports Charts show percentages of EU-27 arable fungicide value 3

4 Waves of new chemistry for sustainable disease control From broad spectrum and low resistance risk to highly specific and high resistance risk Innovation key for solving continuous pathogen adaptation Mixtures: tool for resistance management program and disease control security. 4

5 Industry can come up with new solutions... Costs of new product discovery and development have risen by 39% from

6 $M Costs of ew Product Discovery and Development Total $152 m Development 67 Research 72 Total $184 m Development 79 Total $256 m Development 146 Research 94 Research 85 Registration Environmental Chemistry Toxicology Field Trials Chemistry. Tox/Env Chemistry Biology Chemistry 6 Source: ECPA / Crop Life America 2010

7 Will new chemistry be available to fill the gap? Drivers for Innovation: eed.. Rapid time to Market Have.. Increasing delays (average 6 years) Stable development costs Increasing number, and complexity of new tests Predictable review process Significant uncertainty Return on R&D investment Erosion of data protection rights 7

8 Industry can come up with new solutions... Costs of new product discovery and development have risen by 39% from umber of molecules screened to bring 1 to market is around 140,000. umber of years between first synthesis and market has increased to 9.8 years. Increased registration requirements thus increase cost and impact on development workload and time to market negatively. ew EU regulations raise the hurdles further for new product innovation and are likely to reduce the chances of success. 8

9 Key Fungicide Introductions Year Fungicide thiram, zineb, nabam, biphenyl, oxine copper, tecnazene, captan, folpet, fentin acetate, fentin hydroxide, anilazine, blasticidin S, maneb, dodine, dicloran mancozeb, captafol, dithianon, propineb, thiabendazole, chlorothalonil, dichlofluanid, dodemorph, kasugamycin, polyoxins, pyrazophos, ditalimfos, carboxin, oxycarboxin, drazoxolon, tolyfluanide, difenphos, benomyl, fuberidazole, guazatine, dimethirimol, ethirimol, triforine, tridemorph Iprobenfos, thiophanate, thiophanate-methyl, validamycin, benodanil, triadimefon, imazalil, iprodione, bupirimate, fenarimol, nuarimol, buthiobate, vinclozolin, carbendazim, procymidone, cymoxanil, fosetyl-al, metalaxyl, furalaxyl, triadimenol, prochloraz, ofurace, propamocarb, bitertanol diclobutrazol, etaconazole, propiconazole tolclofos-methy, fenpropimorph benalaxyl, flutolanil, mepronil, pencycuron, cyprofuram, triflumizole, flutriafol, penconazole, flusilazole, diniconazole, oxadixyl, fenpropidin, hexaconazole, cyproconazole, myclobutanil, tebuconazole, pyrifenox, difenoconazole, tetraconazole, fenbuconazole, dimethomorph, fenpiclonil, fludioxonil, epoxyconazole, bromuconazole, pyrimethanil, metconazole, fluquinconazole, triticonazole, fluazinam, azoxystrobin, kresoxim-methyl, metaminostrobin, cyprodinil, mepanipyrim, famoxadone, mefenoxam, quinoxyfen, fenhexamid, fenamidone, trifloxystrobin, cyazofamid (acibenzolar s methyl)

10 Key Fungicide Introductions Year Fungicide present picoxystrobin, pyraclostrobin, prothioconazole, ethaboxam, zoxamide, fluopicolide, flumorph, benthiavalicarb, iprovalicarb, mandipropamid, boscalid, silthiofam, meptyldinocap, amisulbrom, orysastrobin, metrafenone, ipconazole, proquinazid, penthiopyrad, isopyrazam, ametoctradin Future Many known pipeline products ca. 20 Industry continues to invest heavily into providing new innovative solutions, despite increased costs and legislation. Sustainability is essential to maintain this investment 10

11 Fungicide Mode of Action Groups Available for Resistance Management in Wheat (adapted from HGCA, 2010) Rusts S tritici S nodorum Mildew Eyespot Ear Blight DMIs Triazoles **** **** **** ** **** *** QoI Strobilurins **** * **** * * *** Amines Amines *** * *** Chloronitriles Chlorothalonil * *** ** * APDs Cyprodinil **** *** ** Azanaphthalenes Quinoxyfen **** Proquinazid Benzofenone Metrafenone * **** ** Phenylacetamides Cyflufenamid **** Dithiocarbamate Mancozeb * ** ** * Carboxamides Various **** ****? *** ****? (provisional) performance of best fungicides in each class (adapted from HGCA 2010; modified) **** excellent *** very good ** moderate * poor (**** resistance losses) 11 Septoria tritici: Powdery mildew: Very limited possibilities for resistance management Good situation with > 6 modes of action

12 12 So What's ew??

13 Bayer presentation IUPAC Congress Melbourn Classification: ITERAL USE LY

14 ew QoIs -The Strobilurin Family (FRAC Code 11) Company Compound Launch Syngenta azoxystrobin Sales 2008: 895 mio US$* BASF pyraclostrobin Sales 2008: 670 mio US$* Bayer CS trifloxystrobin Sales 2008: 474 mio US$* Kumiai pyribencarb 2010 Shenyang pyrametostrobin Provisionally approved Shenyang coumoxystrobin? Shenyang pyraoxystrobin Provisionally approved Shenyang triclopyricarb? Shenyang dicloaminostrobin? 14 * Phillips McDougall 2009

15 Summary (QoI / Strobilurins) o new breakthrough in the QoI area (new compounds show limited biological potential) All new compounds seem to be x-resistant to the market strobilurins ew compounds might be only of local importance e.g. China 15

16 Complex II Inhibitors SDHI Family Boscalid (BASF) the first broad spectrum SDHI H Cl boscalid Cl Chemical Group Mode of Action Spectrum Characteristics Registration 2002 Pyridine carboxamide (bisphenyltype amide) SDHI (complex II inhibitor) Sales First sales 2003 Alternaria (vegis), botrytis (grapes), sclerotinia (lawn, oilseed rape and lettuce) and eyespot (cereals) Protective, persistent, crop enhancement effects claimed 16 Reinhardsbrunn Symp April 2010

17 Historical verview of SDHIs (source: BASF) Market entry of selected fungicidal SDHI s & their main targets carboxin (Uniroyal) S benodanil (BASF) I fenfuram (Shell/Bayer CS) mepronil (Kumiai) flutolanil (ihon ohyaku) F F F furametpyr (Sumitomo) Cl thifluzamide (Monsanto/Dow) boscalid (BASF) Cl Cl penthiopyrad (Mitsui) fluopyram (Bayer CS) penflufen (Bayer CS) sedaxane (Syngenta) CF 3 CF 3 F S Cl CF 3 CHF 2 seed disinfection (& foliar spray) rice diseases F F F S Br F F F Br specialty crops bixafen (Bayer CS) isopyrazam (Syngenta) CHF 2 Cl CHF 2 Cl F cereals fluxapyroxad (BASF) CHF 2 F F F 17

18 SDHI - Mode of Action AcetylCoA xalacetate Citrate Citrate Cycle Complex II (Succinate Dehydrogenase) Respiration Inhibitor - SDHI 3 H + inside Mitochondrial Membrane outside ADH+H + AD + I Fumarate Succinate Complex II Q 2 e- 2 H + Complex III ½ H + - IV H 2 ADP + P i ATP 2 H + 2 H + 2 H + SDHIs Strobilurins 3 H + 18

19 SDHI s bind to the UQ pocket of SQR of the complex II Essential TCA cycle reaction Isopyrazam F F 2x e - Succinate Ubiquinone n H Septoria tritici SDH inhibition...can be blocked isopyrazam SY 520 (9:1) Bixafen Penthiopyrad 50 Boscalid Fluopyram Log (nm) AI

20 Efficacy of Isopyrazam for control of Septoria tritici IZM 1.0+ EPZ 0.5 IZM 1.0 EPZ 1.0 Untreated % Septoria tritici on leaf 2 (58 DAA2) Source: AGRISEARCH, UK 20 Variety: DUXFRD LSD: Application: GS30-31 (22/04), GS39-41 (14/05),

21 Isopyrazam for control of Septoria tritici IZM 125g+EPZ 90g Location: Terrington, UK Variety: Consort LSD: Applic: GS31/32 (28/04), GS39-45 (21/05) EPZ 90g+Bravo 500g IZM 125g EPZ 125g Untreated Rates: gai/ha % Septoria tritici on leaf 2, 54DAT2 21

22 Improved yields from SDHI chemistry IZM 125g + EPZ 90g Location: Terrington, UK Variety: Consort LSD: 0.97 Applic: GS31/32 (28/04), GS39-45 (21/05) EPZ 90g +Bravo 500g IZM 125g EPZ 125g Untreated Rates: gai/ha Yield (t/ha) 22

23 Isopyrazam Exciting ew Chemistry Untreated IZM, 125 ga/ha 23

24 Trials show outstanding brown rust control with isopyrazam Advantage isopyrazam Advantage 1l/ha high performing triazole Efficacy advantage 24 Source 23 trials various

25 Resistance risk assessment for SDHI fungicides Single site inhibitors Mutations in the target genes (sdh genes) lead to resistance Compound risk is medium to high Putative resistance risk - Mycosphaerella graminicola: medium to high - Pyrenophora teres: medium - Rhynchosporium secalis: low to medium - Puccinia recondita: low - Ramularia collo-cygni: medium SDHIs should always be applied in mixtures or alternations with an appropriate partner i.e. one that is active in its own right against current field populations of the target pathogen at the applied dose 25 Source: Sierotzki et al, Reinhardsbrunn 2010

26 Monitored species / SDHIs and reported cases of resistance Pathogen Field Sensitivity Pathogen Field Sensitivity A. alternata R (US), Pistachio E. necator S B. cinerea R (in grapes and strawberries, apple storage etc.) C. cassiicola R (cucurbits, Japan) M. fijiensis S P. xanthii R (cucurbits) V. inaequalis S M. graminicola S P. teres S R. secalis S R. collo-cygni S S. sclerotiorum S (R, single isolate from SR in 2008 but not re-found (FRAC)) P. leucotricha S Tapesia spp. S M. nivale S U. nuda S? 26

27 SDHI Sensitivity Monitoring 2010 monitoring in cereals (all FRAC Working Group companies) show a continuing fully sensitive situation for SDHIs against all pathogens including M graminicola. All values are within the estabished baseline sensitivity range. o change for isopyrazam since 2004 (start of monitoring). 27 C

28 SDHI FRAC Working Group recommendations SDHI Guidelines Cereals 2011 Apply SDHI fungicides always in mixtures applied as tank mix or as a coformulated mixture The mixture partner: - should provide satisfactory disease control when used alone on the target disease - must have a different mode of action Apply a maximum of 2 SDHI fungicide containing sprays per cereal crop. Apply the SDHI fungicide preventively or as early as possible in the disease cycle. Do not rely only on the curative potential of SDHI fungicides. Strongly reduced rate programs including multiple applications must not be used. Refer to manufacturers recommendations for rates. 28

29 Summary (Broad spectrum Compounds/SDHIs) Boscalid is so far the most significant SDHI in market, in many crops, also used in cereals. Penthiopyrad, bixafen, fluopyram, isopyrazam, fluxapyroxad are broad-spectrum, high potential SDHI fungicides expected to be significant in the market. For seed treatment sedaxane and penflufen are expected. Bixafen, isopyrazam, penthiopyrad, fluxapyroxad used in mixtures with other fungicides expected to be important in cereals based upon published information 29

30 30 WHAT'S EXT AFTER THE SDHIs?

31 What's next? Company published pipeline information shows a number of potential new fungicides, of undisclosed chemistry and mode of action These fungicides may or may not be novel in terms of mode of action Based upon investor presentations alone these seem to be quite some time away from market at present (6-9 years??) There is no guarantee that these willl pass regulatory hurdles and will make it to the market. Key message Industry is continuing to innovate but hurdles are high and it seems we will have to wait a while before the next wave of modes of action for cereals after the SDHIs hits the market. 31

32 Conclusions ew Fungicides for Septoria Control There are few modes of action available for M. graminicola control. The "next generation" of cereal fungicides is based around SDHIs. A very good number of high performing SDHIs will be launched and will need to be managed well to ensure longevity. Triazoles, chlorothalonil etc will be essential for resistance management. Chemistry / MA following the SDHIs, is not yet clear. ew EU regulations raise the hurdles further for new product innovation and are likely to reduce the chances of success.. R&D search criteria will be changed, hazard criteria designed in earlier in the process (will tend to reduce success) Drive to lower performing but lower hazard solutions (not lower risk!) e.g. biologicals 32