Seminar on Emerging Risk Assessment Approaches for Biopesticides | Session 1: Regulatory Considerations for Peptides
OECD_ENV
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Oct 30, 2025
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About This Presentation
The seminar aimed to foster dialogue on emerging risk assessment approaches for biopesticides, and to initiate a process for developing recommendations through the exchange of experiences and challenges faced by governments and stakeholders in this area.
Held over three half-days, the seminar focus...
Slide Content
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Magda Sachana|
Environment Health and Safety Division, Environment
Directorate, OECD
Regulatory Considerations for
Peptides
The 13
th
Expert Group on Biopesticides Seminar
Seminar on Emerging Risk Assessment Approaches for
Biopesticides
February 25
th
, 2025
OECD, Paris
Magda Sachana|
Environment Health and Safety Division, Environment
Directorate, OECD
Regulatory Considerations for
Peptides
The 13
th
Expert Group on Biopesticides Seminar
Seminar on Emerging Risk Assessment Approaches for
Biopesticides
February 25
th
, 2025
OECD, Paris
Restricted Use - À usage restreint
Scientific Breakthroughs on Peptides through
the years
Zhang et al., 2023
Scientific Breakthroughs on Peptides through
the years
Zhang et al., 2023
Restricted Use - À usage restreint
Background
Emerging Peptide Applications in Pest
Control
Naturally occurring and synthetic peptides
can trigger natural plant defense mechanisms
and enhance resistance to diseases and
pests
Regulatory aspects
Data needs and harmonisation of regulatory
approaches
Outlook
Peptide technology is anticipated to grow
significantly, presenting new research and
regulatory opportunities in pest management
Background
Emerging Peptide Applications in Pest
Control
Naturally occurring and synthetic peptides
can trigger natural plant defense mechanisms
and enhance resistance to diseases and
pests
Regulatory aspects
Data needs and harmonisation of regulatory
approaches
Outlook
Peptide technology is anticipated to grow
significantly, presenting new research and
regulatory opportunities in pest management
Restricted Use - À usage restreint
Purpose and scope of session
Information Exchange
among regulators, scientists, and stakeholders to enhance knowledge peptides
Understanding Peptides
Learn about various types of peptides and their potential applications as plant protection products.
Which types fall into the definition of biocontrol agents?
Regulatory Considerations
Identify key considerations for classifying peptides as biocontrol agents and focus on regulatory
needs for risk assessments
Harmonising Approaches
Discuss options for harmonising regulatory assessment approaches for peptides among OECD
member countries
Purpose and scope of session
Information Exchange
among regulators, scientists, and stakeholders to enhance knowledge peptides
Understanding Peptides
Learn about various types of peptides and their potential applications as plant protection products.
Which types fall into the definition of biocontrol agents?
Regulatory Considerations
Identify key considerations for classifying peptides as biocontrol agents and focus on regulatory
needs for risk assessments
Harmonising Approaches
Discuss options for harmonising regulatory assessment approaches for peptides among OECD
member countries
Restricted Use - À usage restreint
Speakers
Research Perspective
Andrea CHINI, National Biotechnology Centre, Spain
Emilio MONTESINOS, Institute of Food and Agricultural, University of
Girona, Spain
Case Studies on Peptides
Eva VAN HENDE, Biotalys
Matthew ORR, Vestaron
Industry Insights
Jennifer LEWIS, IBMA
Emmanuelle BONNERIS, Bayer
Regulatory Considerations
Jacobijn VAN ETTENT, Ctgb, The Netherlands
Emma BABIJ, Health Canada, Canada
Speakers
Research Perspective
Andrea CHINI, National Biotechnology Centre, Spain
Emilio MONTESINOS, Institute of Food and Agricultural, University of
Girona, Spain
Case Studies on Peptides
Eva VAN HENDE, Biotalys
Matthew ORR, Vestaron
Industry Insights
Jennifer LEWIS, IBMA
Emmanuelle BONNERIS, Bayer
Regulatory Considerations
Jacobijn VAN ETTENT, Ctgb, The Netherlands
Emma BABIJ, Health Canada, Canada
Plant Molecular Genetic
National Centre of Biotechnology
[email protected]
Andrea Chini
Natural peptides and
natural-like peptides
Regulatory Considerations for Peptides 25/02/25
National Centre of Biotechnology
[email protected]
Andrea Chini
Natural peptides and
natural-like peptides
Regulatory Considerations for Peptides 25/02/25
Themainaimsofthispresentationare:
1)tolearnaboutthedifferenttypesofpeptidesthat
exist(innature)orareindevelopment
2)identifytheconsiderationsnecessarytoclassify
certainpeptidesasbiocontrolagents
3)definitionofpeptidesasbiocontrolagents
Aim of the discussion
1)tolearnaboutthedifferenttypesofpeptidesthat
exist(innature)orareindevelopment
2)identifytheconsiderationsnecessarytoclassify
certainpeptidesasbiocontrolagents
3)definitionofpeptidesasbiocontrolagents
Aim of the discussion
Themainobjectiveofthispresentationistoopenthe
discussiononwhetherthechanges(editedoroptimised)in
theaminoacidsequenceofnaturalpeptidescanbe
considerednatural-likeand,therefore,theycanfallwithinthe
definitionofbiocontrol.
Aim of the discussion
discussiononwhetherthechanges(editedoroptimised)in
theaminoacidsequenceofnaturalpeptidescanbe
considerednatural-likeand,therefore,theycanfallwithinthe
definitionofbiocontrol.
Aim of the discussion
Definition of natural peptides
Naturalpeptidesareshortchainsofaminoacids,often
arbitrarilyrestrictedtoshortproteinsof2to100amino
acids,thatoccurnaturallyinplant,animalandmicrobialcells.
Naturalpeptidesareshortchainsofaminoacids,often
arbitrarilyrestrictedtoshortproteinsof2to100amino
acids,thatoccurnaturallyinplant,animalandmicrobialcells.
Role of natural peptides in plants
inputoutput
Endogenous
developmental
signals
External biotic
and abiotic
stresses
Development
and growth
Adaptation and
defence
responses
inputoutput
Endogenous
developmental
signals
External biotic
and abiotic
stresses
Development
and growth
Adaptation and
defence
responses
Natural peptides as bioprotectants
Paradigmatic example of natural peptide
Systemin AVQSKPPSKRDPPKMQTD
1 200
Pearce et al., (1991) Science 253:895-898. DOI: 10.1126/science.253.5022.895
Systemin AVQSKPPSKRDPPKMQTD
1 200
Pearce et al., (1991) Science 253:895-898. DOI: 10.1126/science.253.5022.895
Feng et al., (2023) aBIOTECH doi.org/10.1007/s42994-023-00100-0
Biosynthesis of natural peptides
Biosynthesis of natural peptides
Biosynthesis of natural peptides
Montesinos (2023) Annual Review of Phytopathology 61:301-324 doi.org/10.1146/annurev-phyto-021722-034312
Montesinos (2023) Annual Review of Phytopathology 61:301-324 doi.org/10.1146/annurev-phyto-021722-034312
Peptide modifications: natural toolbox
Wenski et al., (2022) Synth Syst Biotechnol. 7:631-647 doi: 10.1016/j.synbio.2022.01.007
Wenski et al., (2022) Synth Syst Biotechnol. 7:631-647 doi: 10.1016/j.synbio.2022.01.007
Current debate on natural-like peptides
Naturalpeptidesarethosederivedfromunmodified
animals,plantsororganismsthroughnaturallyoccurring
processesortraditionalbreeding.
Naturalpeptidesarethosederivedfromunmodified
animals,plantsororganismsthroughnaturallyoccurring
processesortraditionalbreeding.
Framework of natural-like peptides
From few thousand reposted natural peptides
Hundred quintillions of theoretically occurring in nature
(104,857,600,000,000,000,000,000,000)
From few thousand reposted natural peptides
Hundred quintillions of theoretically occurring in nature
(104,857,600,000,000,000,000,000,000)
Yuan et al., (2021) Plant Biotechnology 38, 137–143 DOI: 10.5511/plantbiotechnology.20.0720a
Strategies to identify natural peptides
Analysis of sequence conservation of small peptides
Strategies to identify natural peptides
Analysis of sequence conservation of small peptides
Feng et al., (2023) aBIOTECH doi.org/10.1007/s42994-023-00100-0
Strategies to identify natural peptides
Genome-wide mining
Strategies to identify natural peptides
Genome-wide mining
Wong et al., (2023) Science 381:164-170. doi: 10.1126/science.adh1114
De la Fuente et al., (2023) Nat Chem Biol. 19:1296-1298. doi: 10.1038/s41589-023-01448-6
https://delafuentelab.seas.upenn.edu/
Cesar de la Fuente
Encrypted peptides identified by AI & ML
De la Fuente et al., (2023) Nat Chem Biol. 19:1296-1298. doi: 10.1038/s41589-023-01448-6
https://delafuentelab.seas.upenn.edu/
Cesar de la Fuente
Encrypted peptides identified by AI & ML
Wong et al., (2023) Science 381:164-170. doi: 10.1126/science.adh1114
De la Fuente et al., (2023) Nat Chem Biol. 19:1296-1298. doi: 10.1038/s41589-023-01448-6
https://delafuentelab.seas.upenn.edu/
Cesar de la Fuente
Encrypted peptides
Encrypted peptides identified by AI & ML
De la Fuente et al., (2023) Nat Chem Biol. 19:1296-1298. doi: 10.1038/s41589-023-01448-6
https://delafuentelab.seas.upenn.edu/
Cesar de la Fuente
Encrypted peptides
Encrypted peptides identified by AI & ML
Strategies to identify natural peptides
Ribosome profiling (Ribo-seq)
Libraries construction
& sequencing
Footprint
recovery
Xiao et al., (2018) Nucleic Acids Research doi.org/10.1093/nar/gky179
Ribosome profiling (Ribo-seq)
Libraries construction
& sequencing
Footprint
recovery
Xiao et al., (2018) Nucleic Acids Research doi.org/10.1093/nar/gky179
Strategies to identify natural peptides
Mass spectrometry
Chen et al., (2022) Plant Cell doi/10.1105/tpc.114.131185
Mass spectrometry
Chen et al., (2022) Plant Cell doi/10.1105/tpc.114.131185
Current peptidome knowledge
Onlythetipofthepeptidomeiceberghasbeen
identifiedandthelargeportionofchemicalspace
remainstobeexplored.
Walker et al., (2020) BMC Genomics 21, 387 doi.org/10.1186/s12864-020-06785-7
Onlythetipofthepeptidomeiceberghasbeen
identifiedandthelargeportionofchemicalspace
remainstobeexplored.
Walker et al., (2020) BMC Genomics 21, 387 doi.org/10.1186/s12864-020-06785-7
www.nipgr.ac.in/PlantPepDB/
PlantPepDBisamanuallycurateddatabaseofplantpeptideshavingdifferent
functionsandtherapeuticactivities.Itcontains3,848peptideentries
collectedfrom11databasesand835publishedresearcharticles…
Peptide database tools
Yang et al., (2023) Front. Plant Bioinformatics. doi.org/10.3389/fpls.2023.1224394
PlantPepDBisamanuallycurateddatabaseofplantpeptideshavingdifferent
functionsandtherapeuticactivities.Itcontains3,848peptideentries
collectedfrom11databasesand835publishedresearcharticles…
Peptide database tools
Yang et al., (2023) Front. Plant Bioinformatics. doi.org/10.3389/fpls.2023.1224394
Protein database tools
UniProtisprobablytheworld’sleadinghigh-quality,comprehensiveandfreely
accessibleresourceofproteinsequenceandfunctionalinformation.
UniProtincludes570,420revisedand251,131,474unrevisedproteins.
www.uniprot.org/
www.ebi.ac.uk/pdbe/
UniProtisprobablytheworld’sleadinghigh-quality,comprehensiveandfreely
accessibleresourceofproteinsequenceandfunctionalinformation.
UniProtincludes570,420revisedand251,131,474unrevisedproteins.
www.uniprot.org/
www.ebi.ac.uk/pdbe/
Mode-of-action: peptides in plant protection
Montesinos (2023) Annual Review of Phytopathology 61:301-324 doi.org/10.1146/annurev-phyto-021722-034312
Montesinos (2023) Annual Review of Phytopathology 61:301-324 doi.org/10.1146/annurev-phyto-021722-034312
Synergistic peptides
Özçelik et al., (2023) ACS Chem. Neurosci. 14:3609–3621 doi.org/10.1021/acschemneuro.3c00248
Clarke, et al., (2023) npj Antimicrobials and Resistance 1, 8 doi.org/10.1038/s44259-023-00010-7
Putative function as biocontrol agent elicitor
Özçelik et al., (2023) ACS Chem. Neurosci. 14:3609–3621 doi.org/10.1021/acschemneuro.3c00248
Clarke, et al., (2023) npj Antimicrobials and Resistance 1, 8 doi.org/10.1038/s44259-023-00010-7
Putative function as biocontrol agent elicitor
Amino Acid Substitution of Short Peptides
AminoacidsubstitutioninGHWYYRCW(originalnaturalpeptide)onthe
inhibitionoftheactivityofhumanα-amylaseandα-glucosidaseformedicalstudies.
Yamashita et al., (2020) ACS Biomater. Sci. Eng. 11:6117–6125 doi.org/10.1021/acsbiomaterials.0c01010
AminoacidsubstitutioninGHWYYRCW(originalnaturalpeptide)onthe
inhibitionoftheactivityofhumanα-amylaseandα-glucosidaseformedicalstudies.
Yamashita et al., (2020) ACS Biomater. Sci. Eng. 11:6117–6125 doi.org/10.1021/acsbiomaterials.0c01010
Amino Acid Substitution of Short Peptides
Kim., et al. (2022) Commun Biol 5, 1199 doi.org/10.1038/s42003-022-04164-4
Aminoacidsubstitutiontoimproveactivityofanantimicrobialpeptides
(AMP)ofthenaturalpeptidecoprisinwithunknowntargets.
Kim., et al. (2022) Commun Biol 5, 1199 doi.org/10.1038/s42003-022-04164-4
Aminoacidsubstitutiontoimproveactivityofanantimicrobialpeptides
(AMP)ofthenaturalpeptidecoprisinwithunknowntargets.
Theclassificationofmodified/optimisedpeptidesas
"natural"or"unnatural"isstillamatterofdebate
anditoftendependsonthecontextand
perspectivefromwhichitisconsidered.
Can modified peptides be considered natural-like?
"natural"or"unnatural"isstillamatterofdebate
anditoftendependsonthecontextand
perspectivefromwhichitisconsidered.
Can modified peptides be considered natural-like?
Ifamodifiedplantpeptideisderivedfromnaturallyoccurring
proteinsthroughprocedurethatmimicorenhancenatural
processes(suchasselectiveortraditionalbreedingmethods),it
mightwellbeconsiderednaturaltosomeextent.
Origin and identification
Thisconceptcanbeextendedtopotentiallyencodedpeptides
deducedbylargescalegenomicandtranscriptomicresources.
Genome-wide
mining
proteinsthroughprocedurethatmimicorenhancenatural
processes(suchasselectiveortraditionalbreedingmethods),it
mightwellbeconsiderednaturaltosomeextent.
Origin and identification
Thisconceptcanbeextendedtopotentiallyencodedpeptides
deducedbylargescalegenomicandtranscriptomicresources.
Genome-wide
mining
Optimised/modifiedpeptidesareusuallyobtained
throughgeneticengineeringtechniqueswithintentional
modifications.Theacceptanceofthesemodificationsas
"natural"canvarybasedonregulators.
Genetic modifications
throughgeneticengineeringtechniqueswithintentional
modifications.Theacceptanceofthesemodificationsas
"natural"canvarybasedonregulators.
Genetic modifications
Chemical modifications
Modifiedpeptidescangeneratedby
chemicallyalterationoftheaminoacids
someofwhichoccurinnature(e.g.
phosphorylationornitrosylation)mainly
asregulatorymechanisms.
Incontrast,furtherhuman-promoted
modificationsthatdonotoccurin
naturegenerateunnaturalaminoacids
(UAAs).Suchpeptidesareprimarily
considered"unnatural"sincetheydo
notoccurwithouthumanintervention.
Limorenko & Lashuel (2022) Chem. Soc. Rev., 51:513-565 doi.org/10.1039/D1CS00127B
Modifiedpeptidescangeneratedby
chemicallyalterationoftheaminoacids
someofwhichoccurinnature(e.g.
phosphorylationornitrosylation)mainly
asregulatorymechanisms.
Incontrast,furtherhuman-promoted
modificationsthatdonotoccurin
naturegenerateunnaturalaminoacids
(UAAs).Suchpeptidesareprimarily
considered"unnatural"sincetheydo
notoccurwithouthumanintervention.
Limorenko & Lashuel (2022) Chem. Soc. Rev., 51:513-565 doi.org/10.1039/D1CS00127B
Itisimportanttonotethattheclassificationcanvary,andwhat
isconsiderednaturalinonecontextmightnotbeconsidered
naturalinanother.Inaddition,theregulatorycontexttakes
intoaccountseveralfactorsinadditiontothescientificnotions.
Functional conservation approach
isconsiderednaturalinonecontextmightnotbeconsidered
naturalinanother.Inaddition,theregulatorycontexttakes
intoaccountseveralfactorsinadditiontothescientificnotions.
Functional conservation approach
Severalrecently-developedAI-based3-Dprediction
applications(suchasAlfaFold)areopeningnew
opportunitiestocharacterisetheactivityofnaturalproteins
relayingontheirpredictedthree-dimensionalstructures.
Three-dimensional prediction tools
https://alphafold.ebi.ac.uk/
Jumper et al., (2021) Nature 596:583–589 doi.org/10.1038/s41586-021-03819-2
applications(suchasAlfaFold)areopeningnew
opportunitiestocharacterisetheactivityofnaturalproteins
relayingontheirpredictedthree-dimensionalstructures.
Three-dimensional prediction tools
https://alphafold.ebi.ac.uk/
Jumper et al., (2021) Nature 596:583–589 doi.org/10.1038/s41586-021-03819-2
BenchmarkingAlphaFold2onpeptidestructureprediction
Peptide-specific 3-D prediction tools
https://alphafold.ebi.ac.uk/
Rey et al., (2023) Nucleic Acids Research, 51:W432–437 doi.org/10.1093/nar/gkad376
https://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD4/
Fritz McDonald et al., (2023) Structure 31:111-119.e2 doi.org/10.1016/j.str.2022.11.012
Peptide-specific 3-D prediction tools
https://alphafold.ebi.ac.uk/
Rey et al., (2023) Nucleic Acids Research, 51:W432–437 doi.org/10.1093/nar/gkad376
https://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD4/
Fritz McDonald et al., (2023) Structure 31:111-119.e2 doi.org/10.1016/j.str.2022.11.012
Insummary,theclassificationofnaturalandnatural-likepeptidesisnotan
well-definedanduniversally-acceptedconcept.Conversely,thedefinition
isstillamultifacetedandevolvingnotion
Asscientificresearchadvancescontinue,theregulatoryframeworksalso
evolves,shapingthedefinitionofnatural,natural-likeandunnatural
peptides.Therefore,thisnotioncannotberepresentedasfixedimage
butitshouldbeconsideredasanevolvingconcept.
Final remarks
From few thousand reposted natural peptides
Hundred quintillions of theoretically occurring in nature
(104,857,600,000,000,000,000,000,000)
well-definedanduniversally-acceptedconcept.Conversely,thedefinition
isstillamultifacetedandevolvingnotion
Asscientificresearchadvancescontinue,theregulatoryframeworksalso
evolves,shapingthedefinitionofnatural,natural-likeandunnatural
peptides.Therefore,thisnotioncannotberepresentedasfixedimage
butitshouldbeconsideredasanevolvingconcept.
Final remarks
From few thousand reposted natural peptides
Hundred quintillions of theoretically occurring in nature
(104,857,600,000,000,000,000,000,000)
Emilio Montesinos
Professorof PlantPathology
Universityof Girona
E-mail:[email protected]
Researchgate:www.researchgate.net/profile/Emilio_Montesinos2
The 13th Expert Group on BioPesticides Seminar
on “Emerging Risk Assessment Approaches for Biopesticides”
Session 1 “Regulatory Considerations for Peptides"
Target-oriented functional peptides for plant
disease control. Development and challenges
Professorof PlantPathology
Universityof Girona
E-mail:[email protected]
Researchgate:www.researchgate.net/profile/Emilio_Montesinos2
The 13th Expert Group on BioPesticides Seminar
on “Emerging Risk Assessment Approaches for Biopesticides”
Session 1 “Regulatory Considerations for Peptides"
Target-oriented functional peptides for plant
disease control. Development and challenges
Montesinos, E., Annu.Rev. Phytopathol.
(2023). Vol. 61.
Montesinos E. et al. 2022. ISTE LtD.
A FEW REFERENCES
(2023). Vol. 61.
Montesinos E. et al. 2022. ISTE LtD.
A FEW REFERENCES
Molecular Design
(Structure-function approach)
Peptide Synthesis
(Combinatorial Chemistry
Libraries)
Improved
Peptides
100-1000 new peptides
Leader
Peptides
Hemolyticactivity
Proteasestability
Preliminarytoxicity
Efficacytesting(Proof-of-concept)
Peptides from living organisms
(structure, function, ...)(e.g. cecropin)
HT Screening
Antimicrobial, defence elicitation
Developing analogs and newly designed peptides. Peptide discovery platformΔ
p
H
Time (min)
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
(Structure-function approach)
Peptide Synthesis
(Combinatorial Chemistry
Libraries)
Improved
Peptides
100-1000 new peptides
Leader
Peptides
Hemolyticactivity
Proteasestability
Preliminarytoxicity
Efficacytesting(Proof-of-concept)
Peptides from living organisms
(structure, function, ...)(e.g. cecropin)
HT Screening
Antimicrobial, defence elicitation
Developing analogs and newly designed peptides. Peptide discovery platformΔ
p
H
Time (min)
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
Mechanisms of action of functional peptides. Direct action against pathogens
Figure from Montesinos, E., Annu.Rev. Phytopathol. (2023). Vol. 61.
Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Figure from Montesinos, E., Annu.Rev. Phytopathol. (2023). Vol. 61.
Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
BP100
Ferré et al. 2006. Applied and Environmental Microbiology 72:3302-3308.
Monrocetal.2006.Peptides 27: 2567-2574..
Badosaetal.2007. Peptides.28:2276-2285.
Vilà et al. 2016.PLoS ONE03/2016; 11(3):e0151639.
Baró et al. 2020. Phytopathology 110:1018-1026
Moll L. et al. 2021. Frontiers in Microbiology
Moll L. et al. 2024. Plant Disease.
Target oriented peptides against the pathogens
Lytic Antibiofilm
Anti LPS
PNAs
Antimotility
Obeng E.M. et a. 2017. J Biol. Meth.
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
BP15
Ferré et al. 2006. Applied and Environmental Microbiology 72:3302-3308.
Monrocetal.2006.Peptides 27: 2567-2574..
Badosaetal.2007. Peptides.28:2276-2285.
Vilà et al. 2016.PLoS ONE03/2016; 11(3):e0151639.
Baró et al. 2020. Phytopathology 110:1018-1026
Moll L. et al. 2021. Frontiers in Microbiology
Moll L. et al. 2024. Plant Disease.
Target oriented peptides against the pathogens
Lytic Antibiofilm
Anti LPS
PNAs
Antimotility
Obeng E.M. et a. 2017. J Biol. Meth.
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
BP15
Indirect action. Plant response to elicitor peptides
Figure from Montesinos, E., Annu.Rev. Phytopathol. (2023). Vol. 61. Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Figure from Montesinos, E., Annu.Rev. Phytopathol. (2023). Vol. 61. Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
No antimicrobial activity
Foix, L. et al. 2021. BMC Genomics 22, 360.
Ruíz et al. 2018. BMC Genetics. DOI10.1186/s12863-017-0593-4.
Priming the plant with synthetic endogenous peptides (PEPs)
Consensus sequence of PEPs in 36 species of Rosaceae
EVAAIVLRIKVSRAERPPTSTGSGGQTN
Peach response at transcriptomic lervel after topical treatment
(defence gene overexpression)
PpPep1
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Bacterial spot of
peach control
Foix, L. et al. 2021. BMC Genomics 22, 360.
Ruíz et al. 2018. BMC Genetics. DOI10.1186/s12863-017-0593-4.
Priming the plant with synthetic endogenous peptides (PEPs)
Consensus sequence of PEPs in 36 species of Rosaceae
EVAAIVLRIKVSRAERPPTSTGSGGQTN
Peach response at transcriptomic lervel after topical treatment
(defence gene overexpression)
PpPep1
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Bacterial spot of
peach control
Bifunctional peptides. Lytic and plant defence elicitor activities
Strong plant response to treatment
(defence gene overexpression)
Montesinos, L et al. 2021. Front. Plant Sci. 12:756357.
Moll L. et al. 2022. Phytopathology.
Strong bactericidal activity
Baró et al.,2020. Phytopathology110: 1018-1026
Tomato
Microarray
MBC at <10 ppm
RINSAKDDAAGLQIA
Flagellin 15
KKLFKKILKYLAGPAGIGKFLHSAKKDEL
BP178 (an engineered peptide)
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Almond
RNAseq
Almond scorch disease control
Strong plant response to treatment
(defence gene overexpression)
Montesinos, L et al. 2021. Front. Plant Sci. 12:756357.
Moll L. et al. 2022. Phytopathology.
Strong bactericidal activity
Baró et al.,2020. Phytopathology110: 1018-1026
Tomato
Microarray
MBC at <10 ppm
RINSAKDDAAGLQIA
Flagellin 15
KKLFKKILKYLAGPAGIGKFLHSAKKDEL
BP178 (an engineered peptide)
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Almond
RNAseq
Almond scorch disease control
ACUTE TOXICITY TESTING
The 13th Expert Group on BioPesticides Seminar, Paris 25
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February 2025
Mammals toxicity
Phytotoxicity
Hemolytic activity
Caenorhabditis elegans
nematode
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
Mammals toxicity
Phytotoxicity
Hemolytic activity
Caenorhabditis elegans
nematode
Greenhouse and field tests of plant disease control (Proof-of-concept)
BP100/BP178/BP15 (acetate salt) 150-200 mg a.i./L
PdPEP100 nM
Spray or endotherapy in water solution
Preventative application
Efficacy 50-90%
Erwinia amylovora- apple/pear
Xanthomonas arboricola pv. pruni-peach
P. syringe pv. actinidiae-kiwifruit
Xanthomonas arboricola pv. juglandis-walnut
Xylella fastidiosa- almond
Ca. Liberibacter aisaticus- citrus
Stolbur phytoplasm- potato
Badosa et al. 2007. Peptides.
Badosa et al. 2013. PLOSone
Puig et al. 2015. Plant Disease.
Brown spot of pear (Stemphylium vesicarium)-Field test
Several prokariotic diseases-Greenhouse tests
Rufo et al. 2016. Plant Pathology.
Moll L. et al. 2022. Phytopathology
Montesinos L. et al. 2021. F. Plant Sci.
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
BP100/BP178/BP15 (acetate salt) 150-200 mg a.i./L
PdPEP100 nM
Spray or endotherapy in water solution
Preventative application
Efficacy 50-90%
Erwinia amylovora- apple/pear
Xanthomonas arboricola pv. pruni-peach
P. syringe pv. actinidiae-kiwifruit
Xanthomonas arboricola pv. juglandis-walnut
Xylella fastidiosa- almond
Ca. Liberibacter aisaticus- citrus
Stolbur phytoplasm- potato
Badosa et al. 2007. Peptides.
Badosa et al. 2013. PLOSone
Puig et al. 2015. Plant Disease.
Brown spot of pear (Stemphylium vesicarium)-Field test
Several prokariotic diseases-Greenhouse tests
Rufo et al. 2016. Plant Pathology.
Moll L. et al. 2022. Phytopathology
Montesinos L. et al. 2021. F. Plant Sci.
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
The challenge. Sources and production of functional peptides
Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
Montesinos L. et al. 2017. BMC Plant Biol.
Montesinos L. et al. 2016. PlosOne
Company, N. et al. 2013. Plant Biotech. J.
Ferré R. et al. 2006. Appl. Environ. Microbiol.
Prepared with Biorender
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
Montesinos L. et al. 2017. BMC Plant Biol.
Montesinos L. et al. 2016. PlosOne
Company, N. et al. 2013. Plant Biotech. J.
Ferré R. et al. 2006. Appl. Environ. Microbiol.
Our relevant publications
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
THE TEAM AND FUNDING
E. Badosa L. Montesinos
A. Bonaterra
N. DaranasG. RosellóBea Gascón
M. Pla
Plant pathology
L. Feliu
M. Planas E. Bardají
Peptide chemistry
PepXyl
SmartPepxyl
Current PhD students
Lluís Moll Pau CaravacaA. Buisac
G.Sundin. Michigan State University
L. De la Fuente. Auburn University
T.Dupont/A. Baró. Washington State University
B. Landa. Sustainable Agriculture Institute. CSIC
A.Fereres. Instituto de Ciencias Agrarias. CSIC
M. Saponari, P. Saldarelli. CNR-Bari.
N. Wulff, S. Lopes, B. Sanches. Fundecitrus.
G. Grandchamp, Y. Niu. Invaio.
Collaboration
Funding
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
E. Badosa L. Montesinos
A. Bonaterra
N. DaranasG. RosellóBea Gascón
M. Pla
Plant pathology
L. Feliu
M. Planas E. Bardají
Peptide chemistry
PepXyl
SmartPepxyl
Current PhD students
Lluís Moll Pau CaravacaA. Buisac
G.Sundin. Michigan State University
L. De la Fuente. Auburn University
T.Dupont/A. Baró. Washington State University
B. Landa. Sustainable Agriculture Institute. CSIC
A.Fereres. Instituto de Ciencias Agrarias. CSIC
M. Saponari, P. Saldarelli. CNR-Bari.
N. Wulff, S. Lopes, B. Sanches. Fundecitrus.
G. Grandchamp, Y. Niu. Invaio.
Collaboration
Funding
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
Thanks
https://epsapps.udg.edu/cidsav/
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
https://epsapps.udg.edu/cidsav/
The 13th Expert Group on BioPesticides Seminar, Paris 25
th
February 2025
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Case Study Biotalys
The 13th Expert Group on
BioPesticidesSeminar
on “Emerging Risk Assessment
Approaches for Biopesticides”
February 25
th
, 2025Paris
Dr. ir.Eva Van Hende
Case Study Biotalys
The 13th Expert Group on
BioPesticidesSeminar
on “Emerging Risk Assessment
Approaches for Biopesticides”
February 25
th
, 2025Paris
Dr. ir.Eva Van Hende
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2
Disclaimer
This presentation, including the oral presentation (together, the “Materials”) has been prepared by the management of BiotalysNV (the “Company”). The Materials must be treated confidentially and may not be distributed, passed on or otherwise disclosed.
The Materials serve information purposes only and do not constitute a prospectus or any offer for sale or subscription of, orsolicitation or invitation to buy or subscribe for, any securities of the Company. The Company’s business, operations, financial
situation and prospects are subject to risks and uncertainties. A description of the most important risks and uncertainties canbe found in the Company’s annual report available on its website (www.Biotalys.com)
This presentation includes market share and industry data, which were obtained by the Company from industry publications, press releases, data published by government agencies, industry reports prepared by consultants and other market data providers
and internal surveys. The third party sources the Company has used generally state that the information they contain has beenobtained from sources believed to be reliable. Some of these third party sources also state, however, that the accuracy and
completeness of such information is not guaranteed and that the projections they contain are based on significant assumptions. As the Company does not have access to the facts and assumptions underlying such market data, or statistical information and
economic indicators contained in these third party sources, the Company is unable to verify such information and, while the Company believes it to be reliable, it cannot guarantee its accuracy or completeness.
In addition, certain information in this document is not based on published data obtained from independent third parties or extrapolations therefrom, but rather is based upon the Company's best estimates, which are in turn based upon information obtained
from trade and business organizations and associations, consultants and other contacts within the industries in which the Company operates, information published by its competitors and its own experience and knowledge of conditions and trends in the
markets in which it operates. The Company cannot provide any assurance that any of the assumptions that it has made while compiling this data from third party sources are accurate or correctly reflect its position in the industry and none of its internal
estimates have been verified by any independent sources. The Company makes no representation or warranty as to the accuracy or completeness of this information. The Company has not independently verified this information and, while the Company
believes it to be reliable, it cannot guarantee its accuracy.
You are responsible for protecting yourself against viruses and other destructive items. You are accessing the Materials is at your own risk and it is your responsibility to take precautions to ensure that they are free from viruses or other items of a destructive
nature.
The Materials are provided in conjunction with the oral presentation held by the Company and should not be taken out of context.
The information contained in the Materials is subject to change without prior notice. The presentation of the Materials (or any part hereof) shall not create any implication that there has been no change in the information contained in the Materials since the
date hereof or that there has been no change in the business or financial position of the Company or its subsidiary since thedate hereof. The Company does not undertake to provide any additional information, update or keep current information contained
in the Materials, or to remedy any omissions in or from the Materials and any opinions expressed in the Materials are subjecttochange without prior notice. The foregoing is in any event without prejudice to the Company's obligations under applicable law in
relation to disclosure.
The Materials contain certain forward-looking statements, sometimes identified by the words “believes,” “expects,” “predicts,” “intends,” “projects,” “plans,” “estimates,” “aims,” “foresees,” “anticipates,” “targets,” and similar expressions, which speak only as at
the date of the Materials. Such statements reflect current views with respect to future events and are subject to risks and uncertainties. Forward-looking statements are based on current plans, estimates, projections and expectations. These statements are
based on certain assumptions that may prove to be erroneous. No representations or warranties, express or implied, are given as to the achievement or reasonableness of, and no reliance should be placed on, such forward-looking statements, including
any projections, estimates forecasts or targets contained herein.
Nothing in this presentation constitutes an offer of securities for sale in the EEA, the United Kingdom, Switzerland, Japan, theUnited States or elsewhere. The securities of the Company are not registered under the U.S. Securities Act of 1933, as amended
(the “Securities Act”) and may not be offered, sold or otherwise transferred within the United States (as such term is defined in Regulation S under the Securities Act) unless registered under the Securities Act or pursuant to an exemption from such
registration. There is no intention to register securities of the Company under the Securities Act.
You acknowledge that all industrial and intellectual property rights to this presentation are and shall remain vested in the Company. By attending this presentation or accessing the Materials you shall not acquire any right, title, license to use, or interest in the
presentation or the Materials.
All of the trademarks, service marks and logos displayed in the Materials, including but not limited to Biotalys, AGROBODY, EVOCA are registered and unregistered trademarks of the Company or one of its affiliates. Except as expressly provided in the
Materials, you may not reproduce, display or otherwise use trademarks without first obtaining the Company’s written permission.
Biotalysand each of their logos are commercial names, trademarks or registered trademarks owned by BiotalysNV.
2
Disclaimer
This presentation, including the oral presentation (together, the “Materials”) has been prepared by the management of BiotalysNV (the “Company”). The Materials must be treated confidentially and may not be distributed, passed on or otherwise disclosed.
The Materials serve information purposes only and do not constitute a prospectus or any offer for sale or subscription of, orsolicitation or invitation to buy or subscribe for, any securities of the Company. The Company’s business, operations, financial
situation and prospects are subject to risks and uncertainties. A description of the most important risks and uncertainties canbe found in the Company’s annual report available on its website (www.Biotalys.com)
This presentation includes market share and industry data, which were obtained by the Company from industry publications, press releases, data published by government agencies, industry reports prepared by consultants and other market data providers
and internal surveys. The third party sources the Company has used generally state that the information they contain has beenobtained from sources believed to be reliable. Some of these third party sources also state, however, that the accuracy and
completeness of such information is not guaranteed and that the projections they contain are based on significant assumptions. As the Company does not have access to the facts and assumptions underlying such market data, or statistical information and
economic indicators contained in these third party sources, the Company is unable to verify such information and, while the Company believes it to be reliable, it cannot guarantee its accuracy or completeness.
In addition, certain information in this document is not based on published data obtained from independent third parties or extrapolations therefrom, but rather is based upon the Company's best estimates, which are in turn based upon information obtained
from trade and business organizations and associations, consultants and other contacts within the industries in which the Company operates, information published by its competitors and its own experience and knowledge of conditions and trends in the
markets in which it operates. The Company cannot provide any assurance that any of the assumptions that it has made while compiling this data from third party sources are accurate or correctly reflect its position in the industry and none of its internal
estimates have been verified by any independent sources. The Company makes no representation or warranty as to the accuracy or completeness of this information. The Company has not independently verified this information and, while the Company
believes it to be reliable, it cannot guarantee its accuracy.
You are responsible for protecting yourself against viruses and other destructive items. You are accessing the Materials is at your own risk and it is your responsibility to take precautions to ensure that they are free from viruses or other items of a destructive
nature.
The Materials are provided in conjunction with the oral presentation held by the Company and should not be taken out of context.
The information contained in the Materials is subject to change without prior notice. The presentation of the Materials (or any part hereof) shall not create any implication that there has been no change in the information contained in the Materials since the
date hereof or that there has been no change in the business or financial position of the Company or its subsidiary since thedate hereof. The Company does not undertake to provide any additional information, update or keep current information contained
in the Materials, or to remedy any omissions in or from the Materials and any opinions expressed in the Materials are subjecttochange without prior notice. The foregoing is in any event without prejudice to the Company's obligations under applicable law in
relation to disclosure.
The Materials contain certain forward-looking statements, sometimes identified by the words “believes,” “expects,” “predicts,” “intends,” “projects,” “plans,” “estimates,” “aims,” “foresees,” “anticipates,” “targets,” and similar expressions, which speak only as at
the date of the Materials. Such statements reflect current views with respect to future events and are subject to risks and uncertainties. Forward-looking statements are based on current plans, estimates, projections and expectations. These statements are
based on certain assumptions that may prove to be erroneous. No representations or warranties, express or implied, are given as to the achievement or reasonableness of, and no reliance should be placed on, such forward-looking statements, including
any projections, estimates forecasts or targets contained herein.
Nothing in this presentation constitutes an offer of securities for sale in the EEA, the United Kingdom, Switzerland, Japan, theUnited States or elsewhere. The securities of the Company are not registered under the U.S. Securities Act of 1933, as amended
(the “Securities Act”) and may not be offered, sold or otherwise transferred within the United States (as such term is defined in Regulation S under the Securities Act) unless registered under the Securities Act or pursuant to an exemption from such
registration. There is no intention to register securities of the Company under the Securities Act.
You acknowledge that all industrial and intellectual property rights to this presentation are and shall remain vested in the Company. By attending this presentation or accessing the Materials you shall not acquire any right, title, license to use, or interest in the
presentation or the Materials.
All of the trademarks, service marks and logos displayed in the Materials, including but not limited to Biotalys, AGROBODY, EVOCA are registered and unregistered trademarks of the Company or one of its affiliates. Except as expressly provided in the
Materials, you may not reproduce, display or otherwise use trademarks without first obtaining the Company’s written permission.
Biotalysand each of their logos are commercial names, trademarks or registered trademarks owned by BiotalysNV.
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Key facts
3
Founded in 2013
as spin-off from the
VIB
Based in Belgium,in
the Ghentbiotech
cluster
Building the patent
portfolio
65 FTEs
and16 PhDs
1
Listedon Euronext
Brussels since 2021
AgTechcompany developing novel
protein-based solutions to protect
crops against pests and diseases.
Antibody-based technology already
successfully applied in pharma.
Regulatory review ongoing in the US
and EU for EVOCA
,2
, Biotalys’ first
product aiming to offer fruit &
vegetable growers a new tool to fight
major fungal diseases.
Notes: 1. As of January 2024; 2. EVOCAis pending registration. This product is not currently registered for sale or use in
the US, the EU or elsewhere, and is not being offered for sale
11,3%
Sofinnova
15,4%
AvH
12,6%
AIF
11,5%
Gimv
5,2%
Madeli
44%
Others
Confidential
Key facts
3
Founded in 2013
as spin-off from the
VIB
Based in Belgium,in
the Ghentbiotech
cluster
Building the patent
portfolio
65 FTEs
and16 PhDs
1
Listedon Euronext
Brussels since 2021
AgTechcompany developing novel
protein-based solutions to protect
crops against pests and diseases.
Antibody-based technology already
successfully applied in pharma.
Regulatory review ongoing in the US
and EU for EVOCA
,2
, Biotalys’ first
product aiming to offer fruit &
vegetable growers a new tool to fight
major fungal diseases.
Notes: 1. As of January 2024; 2. EVOCAis pending registration. This product is not currently registered for sale or use in
the US, the EU or elsewhere, and is not being offered for sale
11,3%
Sofinnova
15,4%
AvH
12,6%
AIF
11,5%
Gimv
5,2%
Madeli
44%
Others
Confidential
Restricted Use -À usage restreint
44
•Heavy-chain only antibodies: an
accidental discovery by Prof. Hamers at
the University of Brussels (VUB)
How a failed lab experiment in the early ’90-s changed the world
Prof. R. Hamers: 1932 -2021
AGROBODY Foundrytechnology platform ... a bit of history...
Confidential
44
•Heavy-chain only antibodies: an
accidental discovery by Prof. Hamers at
the University of Brussels (VUB)
How a failed lab experiment in the early ’90-s changed the world
Prof. R. Hamers: 1932 -2021
AGROBODY Foundrytechnology platform ... a bit of history...
Confidential
Restricted Use -À usage restreint
5
Camelids* have 2 types of IgG antibodies
5
Conventional
antibody
Heavy chain only
antibody
Heavy-Chain Heavy-
Chain
Light-Chain
Light-Chain
*Camelids: members of the Camelidae family; e.g. camels, dromedary, llamas, alpacas, vicunas, guanacos
Confidential
5
Camelids* have 2 types of IgG antibodies
5
Conventional
antibody
Heavy chain only
antibody
Heavy-Chain Heavy-
Chain
Light-Chain
Light-Chain
*Camelids: members of the Camelidae family; e.g. camels, dromedary, llamas, alpacas, vicunas, guanacos
Confidential
Restricted Use -À usage restreint
6
AGROBODYVHHs are derived from heavy chain only antibodies
6
Conventional
antibody
Heavy chain only
antibody
Heavy-Chain Heavy-
Chain
Light-Chain
Light-Chain
AGROBODY
TM
bioactive= smallestfunctional fragment of a heavy
chain only antibody (VHH) that is used as biocontrol
NANOBODY
TM
bioactive= smallestfunctional fragment of a heavy
chain only antibody (VHH) that is used as medicinal drug
AGROBODY bioactive
Confidential
6
AGROBODYVHHs are derived from heavy chain only antibodies
6
Conventional
antibody
Heavy chain only
antibody
Heavy-Chain Heavy-
Chain
Light-Chain
Light-Chain
AGROBODY
TM
bioactive= smallestfunctional fragment of a heavy
chain only antibody (VHH) that is used as biocontrol
NANOBODY
TM
bioactive= smallestfunctional fragment of a heavy
chain only antibody (VHH) that is used as medicinal drug
AGROBODY bioactive
Confidential
Restricted Use -À usage restreint
7
AGROBODYVHHs are derived from heavy chain only antibodies
7
Heavy chain only
antibody
AGROBODY
TM
bioactive= smallestfunctional fragment of a
heavy chain only antibody (VHH) that is used as biocontrol
NANOBODY
TM
= smallestfunctional fragment of a heavy chain
only antibody (VHH) that is used as medicinal drug AGROBODY bioactive
Confidential
7
AGROBODYVHHs are derived from heavy chain only antibodies
7
Heavy chain only
antibody
AGROBODY
TM
bioactive= smallestfunctional fragment of a
heavy chain only antibody (VHH) that is used as biocontrol
NANOBODY
TM
= smallestfunctional fragment of a heavy chain
only antibody (VHH) that is used as medicinal drug AGROBODY bioactive
Confidential
Restricted Use -À usage restreint
AGROBODY Foundry-validated platform for the generation
of biocontrolswith excellent agricultural efficacy
•Nature inspired –AGROBODY
TM
biocontrolsderived from special “heavy-chain only” camelid
antibodies
8
Heavy-chain
antibody
High binding capacity & specificity to selected
antigens –designed to have less side-effects
High stability & degradation into natural amino-
acids → Ease of use in natural environments
Multi-deployable
→ One platform for “Infinite” solutions
Manufactured in microbial cellsthrough
fermentation → Scalable, consistent, cost-efficient
Confidential
AGROBODY Foundry-validated platform for the generation
of biocontrolswith excellent agricultural efficacy
•Nature inspired –AGROBODY
TM
biocontrolsderived from special “heavy-chain only” camelid
antibodies
8
Heavy-chain
antibody
High binding capacity & specificity to selected
antigens –designed to have less side-effects
High stability & degradation into natural amino-
acids → Ease of use in natural environments
Multi-deployable
→ One platform for “Infinite” solutions
Manufactured in microbial cellsthrough
fermentation → Scalable, consistent, cost-efficient
Confidential
Restricted Use -À usage restreint
AGROBODYFoundry
9
Pathogen
assessment Nature inspired –boosting
the llama immune system Labin vitro
screening
On planta testing
Cost-effective
manufacturing
Formulation
Commercialization
Field trials &
registration
1 2
3
4
5
6
78
Confidential
AGROBODYFoundry
9
Pathogen
assessment Nature inspired –boosting
the llama immune system Labin vitro
screening
On planta testing
Cost-effective
manufacturing
Formulation
Commercialization
Field trials &
registration
1 2
3
4
5
6
78
Confidential
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10
Confidential
Pathogen
A
AGROBODY A
AGROBODY B
AGROBODY C
Pathogen
B
Pathogen
C2024 2029 2034
Programs in pipelinePrograms registered
7
1
11
3
15
7
Hundreds of
potential MoA
combinations
Total combinations
Source: Data based on company’s own estimates
AGROBODY biocontrolscan
be combined in one “super”
biocontrol
Biotalys is developing +10 different modes of action in the next decade, with the potential to combine these MoAsinto different products
and offer a multitude of unique AGROBODY biocontrol solutions by then
2025
…With the potential to unleash an array of combinations of
different MoAs, opening up major market growth vectors
10
Confidential
Pathogen
A
AGROBODY A
AGROBODY B
AGROBODY C
Pathogen
B
Pathogen
C2024 2029 2034
Programs in pipelinePrograms registered
7
1
11
3
15
7
Hundreds of
potential MoA
combinations
Total combinations
Source: Data based on company’s own estimates
AGROBODY biocontrolscan
be combined in one “super”
biocontrol
Biotalys is developing +10 different modes of action in the next decade, with the potential to combine these MoAsinto different products
and offer a multitude of unique AGROBODY biocontrol solutions by then
2025
…With the potential to unleash an array of combinations of
different MoAs, opening up major market growth vectors
Restricted Use -À usage restreint
Innovative pipeline of biofungicides and bioinsecticides
11
Distribution agreement
Manufacturing agreement
Research agreement
1 new program per year resulting in +10 AGROBODY biocontrolsto be launched on the market by 2040
Program Target Market Discovery
Early
Development
Late
Development
Registration
Partnership
Agreement
EVOCA
1
st
Gen
Botrytis, powdery
mildew
High-value fruits &
vegetables
EVOCA
Next Gen
Botrytis, powdery
mildew
High-value fruits &
vegetables
BioFun-6
Botrytis, powdery
mildew,
Anthracnosis
High-value fruits &
vegetables
Discussions
ongoing
BioFun-7
Cercosporaspp.
(leafspot disease)
Cowpeas and other
legumes
BioFun-4
Oomycetes
(water mold)
Potatoes / High-value
fruits & vegetables
Discussions
ongoing
BioFun-8 Alternaria spp.
Fruits & vegetables and
specialty crops
BioIns-2 Key insect pests Non-disclosed
Confidential
Innovative pipeline of biofungicides and bioinsecticides
11
Distribution agreement
Manufacturing agreement
Research agreement
1 new program per year resulting in +10 AGROBODY biocontrolsto be launched on the market by 2040
Program Target Market Discovery
Early
Development
Late
Development
Registration
Partnership
Agreement
EVOCA
1
st
Gen
Botrytis, powdery
mildew
High-value fruits &
vegetables
EVOCA
Next Gen
Botrytis, powdery
mildew
High-value fruits &
vegetables
BioFun-6
Botrytis, powdery
mildew,
Anthracnosis
High-value fruits &
vegetables
Discussions
ongoing
BioFun-7
Cercosporaspp.
(leafspot disease)
Cowpeas and other
legumes
BioFun-4
Oomycetes
(water mold)
Potatoes / High-value
fruits & vegetables
Discussions
ongoing
BioFun-8 Alternaria spp.
Fruits & vegetables and
specialty crops
BioIns-2 Key insect pests Non-disclosed
Confidential
Restricted Use -À usage restreint
Regulatory packages submitted
12
EVOCA regulatory approval process continues to advance
Future regulatory packages under consideration
Ongoing dialogue with agencies to clarify
outstanding items
Novel nature of the technology requires in-
depth review, but also sets standard for
future approvals of protein-based
biocontrols
Regulatory packages filed in US and EU
Trials executed in the following regions
Confidential
Regulatory packages submitted
12
EVOCA regulatory approval process continues to advance
Future regulatory packages under consideration
Ongoing dialogue with agencies to clarify
outstanding items
Novel nature of the technology requires in-
depth review, but also sets standard for
future approvals of protein-based
biocontrols
Regulatory packages filed in US and EU
Trials executed in the following regions
Confidential
Restricted Use -À usage restreint
Biologicals have changed the rules for the pharmaceutical
industry
•The pharmaceutical industry has undergone a significant transformation over the past few decades, shifting
from a dominance of small-molecule drugs to a strong focus on biologics, particularly monoclonal antibodies.
•Seen as more expensive and less-effective alternative to small molecules in the late ‘90s, biologics today are
taking over drug market sales with no signs of slowing down.
Biologicals are outpacing the growth of small-molecule drugs
13
Ref: The Rise of Biologics: Emerging Trends and Opportunities. CAS
Small molecules
(“chemistry”)
Biologicals
Easy to produce Higher production cost
Stable Degrade faster (compared to
chemicals)
Oral delivery (a pill is more
accepted than a needle)
Not stable in the gut/stomach
➔iv/sc delivery
Promiscuous action: “it gets
everywhere” ➔toxicity
More specific ➔reduced
toxicity, better safety profile
•Progress in biotechnology and a deeper understanding of disease
mechanisms gave way to a revolutionary advancement of biologics.
•The agro-industry is now also making this transition towards biologicals
•Number of antibody therapeutics granted approval is increasing
•>140 antibodies approved in US or EU
•4 Nanobody-based therapies have been approved
•Pipelines of pharmaceutical companies filled with antibodies and
Nanobodies
Confidential
Biologicals have changed the rules for the pharmaceutical
industry
•The pharmaceutical industry has undergone a significant transformation over the past few decades, shifting
from a dominance of small-molecule drugs to a strong focus on biologics, particularly monoclonal antibodies.
•Seen as more expensive and less-effective alternative to small molecules in the late ‘90s, biologics today are
taking over drug market sales with no signs of slowing down.
Biologicals are outpacing the growth of small-molecule drugs
13
Ref: The Rise of Biologics: Emerging Trends and Opportunities. CAS
Small molecules
(“chemistry”)
Biologicals
Easy to produce Higher production cost
Stable Degrade faster (compared to
chemicals)
Oral delivery (a pill is more
accepted than a needle)
Not stable in the gut/stomach
➔iv/sc delivery
Promiscuous action: “it gets
everywhere” ➔toxicity
More specific ➔reduced
toxicity, better safety profile
•Progress in biotechnology and a deeper understanding of disease
mechanisms gave way to a revolutionary advancement of biologics.
•The agro-industry is now also making this transition towards biologicals
•Number of antibody therapeutics granted approval is increasing
•>140 antibodies approved in US or EU
•4 Nanobody-based therapies have been approved
•Pipelines of pharmaceutical companies filled with antibodies and
Nanobodies
Confidential
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AGROBODYbioactives: a unique, identifiable group
14
•Compact size: Approximately 15 kDa
•Structural composition: 9 beta-strands forming a typical IGV fold
•Framework regions: 4 regions with 80% homology to human VH
domains
•3D structural similarity: VHH and human VH structures can be
superimposed
•Complementarity-determining regions (CDRs): 3 regions
•Amino acid substitutions: Occur at four FR2 positions (37, 44, 45, and
47; Kabat numbering)
•Rapid renal filtration: Quick clearance from the blood
•Short serum half-life: Approximately 2 hours
Ref: Asaadi et al. Biomarker Research (2021) 9:87
Confidential
AGROBODYbioactives: a unique, identifiable group
14
•Compact size: Approximately 15 kDa
•Structural composition: 9 beta-strands forming a typical IGV fold
•Framework regions: 4 regions with 80% homology to human VH
domains
•3D structural similarity: VHH and human VH structures can be
superimposed
•Complementarity-determining regions (CDRs): 3 regions
•Amino acid substitutions: Occur at four FR2 positions (37, 44, 45, and
47; Kabat numbering)
•Rapid renal filtration: Quick clearance from the blood
•Short serum half-life: Approximately 2 hours
Ref: Asaadi et al. Biomarker Research (2021) 9:87
Confidential
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15
THANK YOU!!
15
THANK YOU!!
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@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
VP Regulatory
Vestaron Corporation
CASE STUDY
SPEAR® PEPTIDE-
BASED INSECTICIDE
MATT ORR
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@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
VP Regulatory
Vestaron Corporation
CASE STUDY
SPEAR® PEPTIDE-
BASED INSECTICIDE
MATT ORR
@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
2
What are Vestaron Peptides?
Omega/Kappa Peptide
MW 4,571
Inhibitory Cystine Knot (ICK) Peptide
•Peptides are very small proteins.
•They are short, linear sequencesof amino
acids, one of the main building blocks of life.
•Vestaron’s products are derived from
naturally-occurring peptides found in the
venom of spiders, scorpions, and other
animals, giving them unique insecticidal
properties.
•Peptides break down in the environmentinto
amino acids.
2
What are Vestaron Peptides?
Omega/Kappa Peptide
MW 4,571
Inhibitory Cystine Knot (ICK) Peptide
•Peptides are very small proteins.
•They are short, linear sequencesof amino
acids, one of the main building blocks of life.
•Vestaron’s products are derived from
naturally-occurring peptides found in the
venom of spiders, scorpions, and other
animals, giving them unique insecticidal
properties.
•Peptides break down in the environmentinto
amino acids.
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3
❖Chemical name: GS-omega/kappa-Hxtx-Hv1a
❖ MW: 4571 g/mol
❖ IRAC Classification – Group 32 (nAChR Allosteric Modulator – Site II)
❖Spear® is derived from a naturally-occurring peptide found in the venom of the Australian Blue-Mountain
Funnel-web Spider (Hadronyche versuta). The amino acid sequence of the peptide has been modified to
optimize its stability and yield.
❖The product is biologically manufactured via fermentation in a strain of food safe yeast that has been
engineered to express the GS-omega/kappa-Hxtx-Hv1a peptide.
❖The product is efficacious by contact (aphids, mites, whitefly) or by oral ingestion (lepidoptera) when co-
administered with a low dose of Bacillus thuringiensis to facilitate bioavailability.
SPEAR LEP Profile
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3
❖Chemical name: GS-omega/kappa-Hxtx-Hv1a
❖ MW: 4571 g/mol
❖ IRAC Classification – Group 32 (nAChR Allosteric Modulator – Site II)
❖Spear® is derived from a naturally-occurring peptide found in the venom of the Australian Blue-Mountain
Funnel-web Spider (Hadronyche versuta). The amino acid sequence of the peptide has been modified to
optimize its stability and yield.
❖The product is biologically manufactured via fermentation in a strain of food safe yeast that has been
engineered to express the GS-omega/kappa-Hxtx-Hv1a peptide.
❖The product is efficacious by contact (aphids, mites, whitefly) or by oral ingestion (lepidoptera) when co-
administered with a low dose of Bacillus thuringiensis to facilitate bioavailability.
SPEAR LEP Profile
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Bioavailability
Imidacloprid
Molecular weight = 256 g/mol
GS-omega/kappa-Hxtx-Hv1a
Molecular weight = 4565 g/mol
4
1)Bioavailability refers to an active ingredient’s ability to reach the target site and thereby
neutralize the pest.
2)SPEAR
®
, like all proteins, has difficulty permeating the lining of the pest’s stomach after
ingestion so needs a little help.
3)Bacillus Thuringiensis in low doses allows SPEAR to escape the stomach and reach the
target site.
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Bioavailability
Imidacloprid
Molecular weight = 256 g/mol
GS-omega/kappa-Hxtx-Hv1a
Molecular weight = 4565 g/mol
4
1)Bioavailability refers to an active ingredient’s ability to reach the target site and thereby
neutralize the pest.
2)SPEAR
®
, like all proteins, has difficulty permeating the lining of the pest’s stomach after
ingestion so needs a little help.
3)Bacillus Thuringiensis in low doses allows SPEAR to escape the stomach and reach the
target site.
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5
United States
•First registration of the active ingredient granted in 2014
•Product launched in specialty crops in 2019
•Expansion into broad acre row crops in 2023
Mexico – Registration in 2021, product launched in 2022
Canada – Registration and commercial launch in 2023
EU
•Submitted in 2022 with the Netherlands (Ctgb) as rapporteur member state
•Article 53 Emergency Use Authorizations granted in Greece, Italy, and Cyprus in 2024 and 2025
Global Registrations
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5
United States
•First registration of the active ingredient granted in 2014
•Product launched in specialty crops in 2019
•Expansion into broad acre row crops in 2023
Mexico – Registration in 2021, product launched in 2022
Canada – Registration and commercial launch in 2023
EU
•Submitted in 2022 with the Netherlands (Ctgb) as rapporteur member state
•Article 53 Emergency Use Authorizations granted in Greece, Italy, and Cyprus in 2024 and 2025
Global Registrations
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TOXICOLOGY
•No acute toxicity
•Slightly irritating to the skin,
not a sensitizer
•Non-mutagenic, non-
clastogenic, non-aneugenic
•No adverse effects observed
in subchronic (90-day) or
prenatal development studies
in rats
ENVIRONMENTAL FATE
•Readily biodegradable
•Terrestrial half-life < 4 days
(est.)
•Aquatic half-life < 1 day (est.)
•Not a leaching risk
•Biological activity highly
dependent on 3D structure
Regulatory Data Overview
6
ECOTOXICOLOGY
•Practically non-toxic to bees
(EPA cat III)
•No observed adverse effects on
aquatic or terrestrial plants and
animals
•Low impact to beneficial insects
•The use of Bt as a facilitator of
bioavailability confers a high
degree of selectivity to
lepidopteran pests
Favorable environmental and worker-safety profile
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TOXICOLOGY
•No acute toxicity
•Slightly irritating to the skin,
not a sensitizer
•Non-mutagenic, non-
clastogenic, non-aneugenic
•No adverse effects observed
in subchronic (90-day) or
prenatal development studies
in rats
ENVIRONMENTAL FATE
•Readily biodegradable
•Terrestrial half-life < 4 days
(est.)
•Aquatic half-life < 1 day (est.)
•Not a leaching risk
•Biological activity highly
dependent on 3D structure
Regulatory Data Overview
6
ECOTOXICOLOGY
•Practically non-toxic to bees
(EPA cat III)
•No observed adverse effects on
aquatic or terrestrial plants and
animals
•Low impact to beneficial insects
•The use of Bt as a facilitator of
bioavailability confers a high
degree of selectivity to
lepidopteran pests
Favorable environmental and worker-safety profile
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First Active Ingredient
from a Revolutionary
Pest Control Platform
7
First launched in 2020, SPEAR
®
bioinsecticides use a novel
mode of action to affect one of the proven insecticidal
nervous system receptors of target pest insects – the
nicotinic acetylcholine receptor or nAChR.
By harnessing the power of peptides, SPEAR reduces
reliance on synthetic chemicals, benefiting the
environment, workers, and biodiversity in the ecosystem,
while promoting long-term agricultural sustainability.
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First Active Ingredient
from a Revolutionary
Pest Control Platform
7
First launched in 2020, SPEAR
®
bioinsecticides use a novel
mode of action to affect one of the proven insecticidal
nervous system receptors of target pest insects – the
nicotinic acetylcholine receptor or nAChR.
By harnessing the power of peptides, SPEAR reduces
reliance on synthetic chemicals, benefiting the
environment, workers, and biodiversity in the ecosystem,
while promoting long-term agricultural sustainability.
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Commercial Traction in Core U.S. Markets
COMMERCIAL METRICS
8
ACRES SPRAYED OF SPEAR LEP
®
IN CALIFORNIA
1
01
>0.9M acres sprayed across North America
02
Every acre is a 1:1 displacement of synthetic
pesticides with 0 validated complaints
03
Seamless integration into existing crop
protection programs complementing and even
extending use of existing synthetic pesticides
04
Focus markets include fruit, vegetable and nut
crops
05
Manufacturing at scale and profitably
1.Source: Raw Data Analytics
202220212020
36k
75k
126k
↑
67%
↑
107%
167k
↑
33%
2023
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Commercial Traction in Core U.S. Markets
COMMERCIAL METRICS
8
ACRES SPRAYED OF SPEAR LEP
®
IN CALIFORNIA
1
01
>0.9M acres sprayed across North America
02
Every acre is a 1:1 displacement of synthetic
pesticides with 0 validated complaints
03
Seamless integration into existing crop
protection programs complementing and even
extending use of existing synthetic pesticides
04
Focus markets include fruit, vegetable and nut
crops
05
Manufacturing at scale and profitably
1.Source: Raw Data Analytics
202220212020
36k
75k
126k
↑
67%
↑
107%
167k
↑
33%
2023
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Vestaron's Peptides Target the Same Proven Insecticidal
Receptors as Traditional Chemical Insecticides
9
Voltage Gated Sodium Channel
Ryanodine Receptor
Nicotinic Acetylcholine Receptor
Neonicotinoids, Spinosyns
Acetylcholinesterase
Carbamates, Organophosphates
Glutamate-Gated Receptor
Avermectins, Milbemycins
Gaba-Gated Receptor
Cyclodienes, Fiproles
Pyrethroids, DDT, Oxadiazines
Diamides
$
4.7b
$
3.1b
$
2.3b
$
2.3b
$0.7b
$
1.3b
COMMERCIAL
IN DEVELOPMENT
VESTARON PRODUCTS KEY
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Vestaron's Peptides Target the Same Proven Insecticidal
Receptors as Traditional Chemical Insecticides
9
Voltage Gated Sodium Channel
Ryanodine Receptor
Nicotinic Acetylcholine Receptor
Neonicotinoids, Spinosyns
Acetylcholinesterase
Carbamates, Organophosphates
Glutamate-Gated Receptor
Avermectins, Milbemycins
Gaba-Gated Receptor
Cyclodienes, Fiproles
Pyrethroids, DDT, Oxadiazines
Diamides
$
4.7b
$
3.1b
$
2.3b
$
2.3b
$0.7b
$
1.3b
COMMERCIAL
IN DEVELOPMENT
VESTARON PRODUCTS KEY
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@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
Unconventional, by nature.
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@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
Unconventional, by nature.
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Reviewing the
definition of biocontrol
in light ofnew peptide
technologies for plant
protection
Jennifer Lewis
Emmanuelle Bonneris
Reviewing the
definition of biocontrol
in light ofnew peptide
technologies for plant
protection
Jennifer Lewis
Emmanuelle Bonneris
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Summary
•Introduction –what is biocontrol
•How to manage innovation in biocontrol
•The way to approach regulation of this technology
•Conclusion
Summary
•Introduction –what is biocontrol
•How to manage innovation in biocontrol
•The way to approach regulation of this technology
•Conclusion
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Introduction
Introduction
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The 4 types of biocontrol: invertebrates, microbials, semiochemicalsand natural
substances which includes proteins and peptides
4
Semiochemicals
Microbials Natural substances
Invertebrates
The 4 types of biocontrol: invertebrates, microbials, semiochemicalsand natural
substances which includes proteins and peptides
4
Semiochemicals
Microbials Natural substances
Invertebrates
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IBMA Definition of Natural Substances
Natural substances consist of one or more components that
originate from nature, including but not limited to: plants,
algae/microalgae, animals, minerals, bacteria, fungi,
protozoans, peptides, proteins (e.g. enzymes, antibodies),
viruses, viroids, and mycoplasmas. They can either be
sourced from nature or are nature identical if synthetized.
This definition excludes semiochemicals and microbials,
which have their own defintion.
5
IBMA Definition of Natural Substances
Natural substances consist of one or more components that
originate from nature, including but not limited to: plants,
algae/microalgae, animals, minerals, bacteria, fungi,
protozoans, peptides, proteins (e.g. enzymes, antibodies),
viruses, viroids, and mycoplasmas. They can either be
sourced from nature or are nature identical if synthetized.
This definition excludes semiochemicals and microbials,
which have their own defintion.
5
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How to
manage
innovation in
biocontrol
How to
manage
innovation in
biocontrol
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Peptides and Proteins as Novel Crop Protection Products
7
•New uses of proteins and peptides are
emerging for pest and disease control
including
•Plant elicitor technology – eg Harpin proteins
•Antibodies for pest and disease control eg
Biotalys portfolio
•Spider venom peptides for insect control eg
Vestaron portfolio
•Many are identical to nature while others
have small modifications to improve some
aspect of their application eg shelf life
Peptides and Proteins as Novel Crop Protection Products
7
•New uses of proteins and peptides are
emerging for pest and disease control
including
•Plant elicitor technology – eg Harpin proteins
•Antibodies for pest and disease control eg
Biotalys portfolio
•Spider venom peptides for insect control eg
Vestaron portfolio
•Many are identical to nature while others
have small modifications to improve some
aspect of their application eg shelf life
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Examples of Peptide innovations
Harpin and PRETec (Plant
Response Elicitor
Technologies) and PHC-
91398 a growth regulator
FLG22 induces the natural
immune response
Computational biology & AI to
ID micropeptides
Peptide maSAMP for
Huanglongbing
Bialaphosa tripeptide
herbicide
Neuropeptide
bioinsecticideSpear® derived
from Spider venom
Hicure® peptides is a natural
biostimulant
Opportune herbicide Agrobodies for pest and
diseases: Evoca for Botrytis
Antimicrobial peptide (AMP)
technology
Problad Plus a biofungicide Plant-derived peptide LRPP is
a biostimulant
Insect neuropeptides
disturbing target physiology
for pest kill
Antifungal peptide platform
InnaLB, InnaNema,
InnaHLB
8
Modified from Pam Marrone
Examples of Peptide innovations
Harpin and PRETec (Plant
Response Elicitor
Technologies) and PHC-
91398 a growth regulator
FLG22 induces the natural
immune response
Computational biology & AI to
ID micropeptides
Peptide maSAMP for
Huanglongbing
Bialaphosa tripeptide
herbicide
Neuropeptide
bioinsecticideSpear® derived
from Spider venom
Hicure® peptides is a natural
biostimulant
Opportune herbicide Agrobodies for pest and
diseases: Evoca for Botrytis
Antimicrobial peptide (AMP)
technology
Problad Plus a biofungicide Plant-derived peptide LRPP is
a biostimulant
Insect neuropeptides
disturbing target physiology
for pest kill
Antifungal peptide platform
InnaLB, InnaNema,
InnaHLB
8
Modified from Pam Marrone
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Expert review of state of the art of peptide innovations
9
Dr. Andrea Chini (National Center for Biotechnology (CNB/CSIC)) was engaged to open the discussion on
whether the changes (edited or optimised) in the amino acid sequence of natural peptides can be
considered nature identical and, therefore, they can fall within the IBMA-developed definition of biocontrol.
Expert review of state of the art of peptide innovations
9
Dr. Andrea Chini (National Center for Biotechnology (CNB/CSIC)) was engaged to open the discussion on
whether the changes (edited or optimised) in the amino acid sequence of natural peptides can be
considered nature identical and, therefore, they can fall within the IBMA-developed definition of biocontrol.
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Review concluded there is no clear cut definition relating
to nature identicality for peptides
10
Review concluded there is no clear cut definition relating
to nature identicality for peptides
10
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Innovation– Process for reviewing new technology
11
Sept
2023 2024
Academic
expert engaged
to review case
for re-
engineered
peptides to be
considered
nature identical
Nov
Jan-
April
May June June Sept Oct
Scoping Committee
confirmed inclusion
of identical peptides
and proteins and
requested more
information from
Natural Substances
PG
Natural Substances
Professional
Group–subgroup
on definitions
prepare
background
document
Review of
background
document by
academic
expert
Natural
Substances
Professional
Group workshop
– Review of
background
document
Scoping
committee
review – agree
conditions under
which
modifications to
peptides and
proteins can be
deemed nature
identical
Natural
Substances PG –
subgroup on
definitions
revise
background
document
Natural
Substances
Professional
Group finalise
background
paper for
submission to
Council
Scoping Committee = Council Members and the Technical Project Manager with specialist advice from
scientific experts as required.
Innovation– Process for reviewing new technology
11
Sept
2023 2024
Academic
expert engaged
to review case
for re-
engineered
peptides to be
considered
nature identical
Nov
Jan-
April
May June June Sept Oct
Scoping Committee
confirmed inclusion
of identical peptides
and proteins and
requested more
information from
Natural Substances
PG
Natural Substances
Professional
Group–subgroup
on definitions
prepare
background
document
Review of
background
document by
academic
expert
Natural
Substances
Professional
Group workshop
– Review of
background
document
Scoping
committee
review – agree
conditions under
which
modifications to
peptides and
proteins can be
deemed nature
identical
Natural
Substances PG –
subgroup on
definitions
revise
background
document
Natural
Substances
Professional
Group finalise
background
paper for
submission to
Council
Scoping Committee = Council Members and the Technical Project Manager with specialist advice from
scientific experts as required.
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IBMA Scoping Committee Conclusion: When certain conditions
are met modified peptides/proteins are biocontrol
12
Natural substances consist of one or more components that originate from nature, including but not limited
to: plants, algae/microalgae, animals, minerals, bacteria, fungi, protozoans, peptides, proteins (e.g.
enzymes, antibodies), viruses, viroids, and mycoplasmas. They can either be sourced from nature or are
nature identical if synthetized. This definition excludes semiochemicals and microbials, which have their
own definition.
Among natural substances, IBMA considers that peptides and proteins containing sequence modifications of
a peptide/protein sourced from nature are deemed nature-identical provided all of the following conditions
are met
(1)they contain only naturally occurring amino-acids
(2)such modifications do not change the 3-dimensional structure
(3)such modifications do not change the biological function and
(4)the biological breakdown occurs in a predicted way according to a natural pathway.
IBMA Scoping Committee Conclusion: When certain conditions
are met modified peptides/proteins are biocontrol
12
Natural substances consist of one or more components that originate from nature, including but not limited
to: plants, algae/microalgae, animals, minerals, bacteria, fungi, protozoans, peptides, proteins (e.g.
enzymes, antibodies), viruses, viroids, and mycoplasmas. They can either be sourced from nature or are
nature identical if synthetized. This definition excludes semiochemicals and microbials, which have their
own definition.
Among natural substances, IBMA considers that peptides and proteins containing sequence modifications of
a peptide/protein sourced from nature are deemed nature-identical provided all of the following conditions
are met
(1)they contain only naturally occurring amino-acids
(2)such modifications do not change the 3-dimensional structure
(3)such modifications do not change the biological function and
(4)the biological breakdown occurs in a predicted way according to a natural pathway.
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Emmanuelle Bonneris
Chair of IBMA Natural
Substances Professional Group,
Bayer
The way to
approach
regulation
ofthis
technology
Emmanuelle Bonneris
Chair of IBMA Natural
Substances Professional Group,
Bayer
The way to
approach
regulation
ofthis
technology
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How to regulatethistechnology?
1) Use a specific strategy suited to the unique characteristics
of each protein category in considering the outcome of
different initiatives at OECD and in different regions of the
world, ref., Problem Formulation for the Risk Assessment of
BioPesticides, 26 February 2024 (OECD)
Due to the large differences amongst proteins and peptides, assessments conducted for new proteins or
peptides technologies should:
2) Establish criteria on how to address areas of potential
adverse effects (harms) for these specific technologies via
problem formulation approach:
-Is it a targeted MoA? How is the peptide produced? Does
the peptide already have a recognized specification (e.g
food/feed use)?
-Is the peptide to be approved of potential human concern
triggering testing?
-Is the peptide readily biodegradable?
-Is organisms group (habitat) expected to be exposed
(depending on protection goals)?
4) Use relevant new approach methodologies where possible
to avoid unnecessary testing (incl. animal studies), some
being adapted for the peptide technology (in vitro or in silico
methods suitable?)
3) Use published data available (e.g., EPA Doc. and
preliminary literature review), e.g. acute studies available for
US dossier (Weight-of-Evidence) approach to be presented
in RMS pre-submission meeting for discussion to avoid
repeating studies in EU
Goal:
Harmonized
approach to
evaluate protein
technologies
How to regulatethistechnology?
1) Use a specific strategy suited to the unique characteristics
of each protein category in considering the outcome of
different initiatives at OECD and in different regions of the
world, ref., Problem Formulation for the Risk Assessment of
BioPesticides, 26 February 2024 (OECD)
Due to the large differences amongst proteins and peptides, assessments conducted for new proteins or
peptides technologies should:
2) Establish criteria on how to address areas of potential
adverse effects (harms) for these specific technologies via
problem formulation approach:
-Is it a targeted MoA? How is the peptide produced? Does
the peptide already have a recognized specification (e.g
food/feed use)?
-Is the peptide to be approved of potential human concern
triggering testing?
-Is the peptide readily biodegradable?
-Is organisms group (habitat) expected to be exposed
(depending on protection goals)?
4) Use relevant new approach methodologies where possible
to avoid unnecessary testing (incl. animal studies), some
being adapted for the peptide technology (in vitro or in silico
methods suitable?)
3) Use published data available (e.g., EPA Doc. and
preliminary literature review), e.g. acute studies available for
US dossier (Weight-of-Evidence) approach to be presented
in RMS pre-submission meeting for discussion to avoid
repeating studies in EU
Goal:
Harmonized
approach to
evaluate protein
technologies
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Data requirements on a “need to know basis” –
environmental safety
Considerations for proteins/peptides
•Targeted MoA or non- toxic MoA: e.g harpin peptides trigger natural defense mechanisms in
plants.
•Intended use including application methods
•Natural occurrence
•Phys-chem and biological properties
•Well documented and reported (already regulatory approval for other uses with data package)
Instead of establishing minimum risk in all possible aspects of environmental risk the scope is to:
(1)Use all available information to create conceptual model for potential hazards and exposure
e.g. properties of the substance, literature, intended use pattern, stability, read-across to
comparable substances, experience from established uses
(2) Target the assessment to species which could be affected by the mode of action of the
substance AND will be exposed based on the intended application method.
→ In line with problem formulation principles
Are there plausible
pathways to harm?
How are these been
assessed?
Data requirements on a “need to know basis” –
environmental safety
Considerations for proteins/peptides
•Targeted MoA or non- toxic MoA: e.g harpin peptides trigger natural defense mechanisms in
plants.
•Intended use including application methods
•Natural occurrence
•Phys-chem and biological properties
•Well documented and reported (already regulatory approval for other uses with data package)
Instead of establishing minimum risk in all possible aspects of environmental risk the scope is to:
(1)Use all available information to create conceptual model for potential hazards and exposure
e.g. properties of the substance, literature, intended use pattern, stability, read-across to
comparable substances, experience from established uses
(2) Target the assessment to species which could be affected by the mode of action of the
substance AND will be exposed based on the intended application method.
→ In line with problem formulation principles
Are there plausible
pathways to harm?
How are these been
assessed?
Restricted Use - À usage restreint
Data requirements on a “need to know basis”
– General considerations for proteins/peptides
Identification of
relevant risk areas to
address, i.e.,
Toxicology, Residues,
Ecotoxicology,
Environmental fate
Is there potential
for exposure to
relevant species
susceptible to
cause an
unacceptable
effect ?
No
Risk is
concluded
as low
Yes,
may be so
which data can
be required to
generate?
For Toxicology, Ecotoxicology, and Environmental fate: Tiered
approach: Acute/base studies may be required as chronic tests -
waiving is possible if MoA can show no possible relevant exposure
Specific tests may be required, e.g., analysis of residual antimicrobial
activity, detection and quantification of Plasmid DNA, Survival of PPP
Production Cell line, quantification of agglomerated % active
ingredient, analysis of potential gene resistance
Early engagement with regulatory authorities is essential to discuss testing strategy, waivers and WoE assessments
Data requirements on a “need to know basis”
– General considerations for proteins/peptides
Identification of
relevant risk areas to
address, i.e.,
Toxicology, Residues,
Ecotoxicology,
Environmental fate
Is there potential
for exposure to
relevant species
susceptible to
cause an
unacceptable
effect ?
No
Risk is
concluded
as low
Yes,
may be so
which data can
be required to
generate?
For Toxicology, Ecotoxicology, and Environmental fate: Tiered
approach: Acute/base studies may be required as chronic tests -
waiving is possible if MoA can show no possible relevant exposure
Specific tests may be required, e.g., analysis of residual antimicrobial
activity, detection and quantification of Plasmid DNA, Survival of PPP
Production Cell line, quantification of agglomerated % active
ingredient, analysis of potential gene resistance
Early engagement with regulatory authorities is essential to discuss testing strategy, waivers and WoE assessments
@ 2 0 2 4 V E S T A R O N C O R P O R A T I O N . A L L R I G H T S R E S E R V E D
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TOXICOLOGY
•No acute toxicity
•Slightly irritating to the skin,
not a sensitizer
•Non-mutagenic, non-
clastogenic, non-aneugenic
•No adverse effects observed
in subchronic (90-day) or
prenatal development studies
in rats
ENVIRONMENTAL FATE
•Readily biodegradable
•Terrestrial half-life < 4 days
(est.)
•Aquatic half-life < 1 day (est.)
•Not a leaching risk
•Biological activity highly
dependent on 3D structure
Regulatory Data Overview (Case 1)
17
ECOTOXICOLOGY
•Practically non-toxic to bees
(EPA cat III)
•No observed adverse effects on
aquatic or terrestrial plants and
animals
•Low impact to beneficial insects
•The use of Bt as a facilitator of
bioavailability confers a high
degree of selectivity to
lepidopteran pests
Favorable environmental and worker-safety profile
Bacillus Thuringiensis in low
doses allows SPEAR to escape
the pest stomach and reach the
target site.
Restricted Use - À usage restreint
TOXICOLOGY
•No acute toxicity
•Slightly irritating to the skin,
not a sensitizer
•Non-mutagenic, non-
clastogenic, non-aneugenic
•No adverse effects observed
in subchronic (90-day) or
prenatal development studies
in rats
ENVIRONMENTAL FATE
•Readily biodegradable
•Terrestrial half-life < 4 days
(est.)
•Aquatic half-life < 1 day (est.)
•Not a leaching risk
•Biological activity highly
dependent on 3D structure
Regulatory Data Overview (Case 1)
17
ECOTOXICOLOGY
•Practically non-toxic to bees
(EPA cat III)
•No observed adverse effects on
aquatic or terrestrial plants and
animals
•Low impact to beneficial insects
•The use of Bt as a facilitator of
bioavailability confers a high
degree of selectivity to
lepidopteran pests
Favorable environmental and worker-safety profile
Bacillus Thuringiensis in low
doses allows SPEAR to escape
the pest stomach and reach the
target site.
Restricted Use - À usage restreint
What are our needs to support faster approval
of proteins/peptides? - General considerations
New peptide technologies are so diverse in types, e.g. neuropeptides, antibodies, harpin protein that:
•We need a strong regulatory framework following a problem formulation approach to guide development
of relevant data package for worldwide approvals of proteins/peptides
•We need alignment within different initiatives amongst problem formulation to ensure consistency on how
we want to regulate peptides technologies.
•We need data requirements and specific guidance documents for novel technologies such as
proteins/peptides in the OECD program.
•We need pre-submission consultations guidance on the information/data requirements and to facilitate
the submission of a more complete data package/dossier which will in turn facilitate the review and
decision-making process.
•We need procedures able to accelerate approvals of these technologies especially when already registered
out of Europe.
What are our needs to support faster approval
of proteins/peptides? - General considerations
New peptide technologies are so diverse in types, e.g. neuropeptides, antibodies, harpin protein that:
•We need a strong regulatory framework following a problem formulation approach to guide development
of relevant data package for worldwide approvals of proteins/peptides
•We need alignment within different initiatives amongst problem formulation to ensure consistency on how
we want to regulate peptides technologies.
•We need data requirements and specific guidance documents for novel technologies such as
proteins/peptides in the OECD program.
•We need pre-submission consultations guidance on the information/data requirements and to facilitate
the submission of a more complete data package/dossier which will in turn facilitate the review and
decision-making process.
•We need procedures able to accelerate approvals of these technologies especially when already registered
out of Europe.
Restricted Use - À usage restreint
Options for the Future to faster approvals of proteins
Current Situation
Pathogen
A
AGROBODY A
AGROBODY B
AGROBODY C
Pathogen
B
Pathogen
CCoformulant
TG
AI
Bioprocess related
non-relevant
components
Agrobody
Evoca
TM
Future Situation
Production processes will be
optimized, multiple
AGROBODIES will follow
Options for the Future
Consider alternative regions
Structural Read Across?
https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efs
a.2011.EN-159
Group registration(like SCLP) forallVHHs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237237/
Or …one by one…?
Discussion/Brainstorm:
What are your
thoughts?
Case 2: Natural-identical single entities (Agrobodies
TM
case)
Options for the Future to faster approvals of proteins
Current Situation
Pathogen
A
AGROBODY A
AGROBODY B
AGROBODY C
Pathogen
B
Pathogen
CCoformulant
TG
AI
Bioprocess related
non-relevant
components
Agrobody
Evoca
TM
Future Situation
Production processes will be
optimized, multiple
AGROBODIES will follow
Options for the Future
Consider alternative regions
Structural Read Across?
https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efs
a.2011.EN-159
Group registration(like SCLP) forallVHHs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237237/
Or …one by one…?
Discussion/Brainstorm:
What are your
thoughts?
Case 2: Natural-identical single entities (Agrobodies
TM
case)
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At EU-level: Group registration for all VHHs
including different manufacturing methods
(=different production hosts. 5-batch (or 3?) done
for each host)
At Zonal level: Product registration for specific
VHH
differences are shown with following data:
-In silico experiments of the MoA
-Sequence of the specific VHH
-Efficacy (but limit the climatic zones)
How might it look? Arguments?
-VHHs are a well-defined category of proteins with the same 3D-folding
structure
-They differ in their variable domain only
-Degradation pattern will be similar between VHHs
-Hazard profile will be similar between VHHs
-The same VHH can be produced from different microbial sources. Wide
specifications can help to help set the best method for each VHH.
-Production by fermentation is constantly improved. % Bioprocess related
material will decrease with time.
-Mode of Action, Sequence and Efficacy will be different for each VHH
Case 2: Natural-identical single entities (Agrobodies
TM
case)
Options for the Future to faster approvals of proteins
At EU-level: Group registration for all VHHs
including different manufacturing methods
(=different production hosts. 5-batch (or 3?) done
for each host)
At Zonal level: Product registration for specific
VHH
differences are shown with following data:
-In silico experiments of the MoA
-Sequence of the specific VHH
-Efficacy (but limit the climatic zones)
How might it look? Arguments?
-VHHs are a well-defined category of proteins with the same 3D-folding
structure
-They differ in their variable domain only
-Degradation pattern will be similar between VHHs
-Hazard profile will be similar between VHHs
-The same VHH can be produced from different microbial sources. Wide
specifications can help to help set the best method for each VHH.
-Production by fermentation is constantly improved. % Bioprocess related
material will decrease with time.
-Mode of Action, Sequence and Efficacy will be different for each VHH
Case 2: Natural-identical single entities (Agrobodies
TM
case)
Options for the Future to faster approvals of proteins
Restricted Use - À usage restreint
Conclusion
Conclusion
Restricted Use - À usage restreint
Conclusion
22
Proteins and peptides are naturally occurring modern crop protection tools that fall within the
biocontrol definition
Peptides known today are the tip of the iceberg – many more to discover
IBMA considers that peptides with small modifications can be deemed nature identical if certain
structural and functional conditions are met
Regulatory frameworks should follow a “need to know” decision tree approach enabling faster
authorisation while ensuring a full safety evaluation
Faster authorisation is necessary to bring more biocontrol to market to accelerate the transition
to a more sustainable agriculture
Conclusion
22
Proteins and peptides are naturally occurring modern crop protection tools that fall within the
biocontrol definition
Peptides known today are the tip of the iceberg – many more to discover
IBMA considers that peptides with small modifications can be deemed nature identical if certain
structural and functional conditions are met
Regulatory frameworks should follow a “need to know” decision tree approach enabling faster
authorisation while ensuring a full safety evaluation
Faster authorisation is necessary to bring more biocontrol to market to accelerate the transition
to a more sustainable agriculture
Restricted Use - À usage restreint
IBMA
International Biocontrol Manufacturers Association AISBL
Rue de Trèves 61
1040 Brussels
Belgium
WWW.IBMA-GLOBAL.ORG
Thank you
Emmanuelle Bonneris
[email protected]
CHAIR
Marisé Borja
[email protected]
VICE CHAIR
Natural Substances
Working Group
(NSPG)
IBMA
International Biocontrol Manufacturers Association AISBL
Rue de Trèves 61
1040 Brussels
Belgium
WWW.IBMA-GLOBAL.ORG
Thank you
Emmanuelle Bonneris
[email protected]
CHAIR
Marisé Borja
[email protected]
VICE CHAIR
Natural Substances
Working Group
(NSPG)
Regulatory challenges for peptides
within plant protection products
and how they are resolved
Jacobijn van Etten, withinput fromtheGreenTEAM
The 13th Expert Group on BioPesticidesSeminar OECD 25-02-2025
within plant protection products
and how they are resolved
Jacobijn van Etten, withinput fromtheGreenTEAM
The 13th Expert Group on BioPesticidesSeminar OECD 25-02-2025
Ctgb GreenTEAM
Dedicated team working on biopesticides:
•11 experts
•3 project managers
•1 policy officer
•1 team leader
2024:
•8 active substances submitted for Peer Review +
•9 product authorisations(both extensions and new products)
Dedicated team working on biopesticides:
•11 experts
•3 project managers
•1 policy officer
•1 team leader
2024:
•8 active substances submitted for Peer Review +
•9 product authorisations(both extensions and new products)
Peptidesin plant protection
Peptides in Agriculture:
oSmall protein molecules (typically consisting of 2-50 amino acids).
oCan act as e.g., antimicrobial agents, insecticides, plant defense enhancer, or
growth regulators.
Emerging Interest:
oThe hazard profile of peptides in agriculture is generally favorable due to their
specificity, biodegradability, and low toxicity to non-target organisms.
Peptides in Agriculture:
oSmall protein molecules (typically consisting of 2-50 amino acids).
oCan act as e.g., antimicrobial agents, insecticides, plant defense enhancer, or
growth regulators.
Emerging Interest:
oThe hazard profile of peptides in agriculture is generally favorable due to their
specificity, biodegradability, and low toxicity to non-target organisms.
Peptidesin PPP
•First dossiers in EU Regulatory system: antibodies for control of plant pathogenic
fungi and (poly)peptides for insect control
•In European context: Regulation (EC) No 1107/2009 for plant protection products is
applicable and a dossier for a peptide should comply with data requirements for
chemical active substances (i.e., part A)
•Peptides (and otheraminoacid-basedpolymeres)have different characteristics
compared to conventional chemical active substances
•First dossiers in EU Regulatory system: antibodies for control of plant pathogenic
fungi and (poly)peptides for insect control
•In European context: Regulation (EC) No 1107/2009 for plant protection products is
applicable and a dossier for a peptide should comply with data requirements for
chemical active substances (i.e., part A)
•Peptides (and otheraminoacid-basedpolymeres)have different characteristics
compared to conventional chemical active substances
Challengeswithpeptides
•TGAI can be complex mixture:
–How to set specification (98% characterization may not be needed;
information should be sufficient to cover risk and efficacy assessment);
–Relevance of other compounds?
–How to address leaching assessment?
•How to address data requirements on the route of degradation? (Is information
relevant –route is known for peptides in general; how to adjust tests?)
•Tertiary structure is crucial; how to demonstrate that structure in test item for
human health/ecotoxtesting (and efficacy) is intact? (e.g., influence of pH,
desiccation)
•Ecotoxicological tests may be difficult due to rapid degradation
•TGAI can be complex mixture:
–How to set specification (98% characterization may not be needed;
information should be sufficient to cover risk and efficacy assessment);
–Relevance of other compounds?
–How to address leaching assessment?
•How to address data requirements on the route of degradation? (Is information
relevant –route is known for peptides in general; how to adjust tests?)
•Tertiary structure is crucial; how to demonstrate that structure in test item for
human health/ecotoxtesting (and efficacy) is intact? (e.g., influence of pH,
desiccation)
•Ecotoxicological tests may be difficult due to rapid degradation
Assessment (poly)peptidesand proteins
•Alternative approaches to address data requirements may be needed
•Highly divergent properties of peptides –no one-size-fits-all approach possible
•Information on the mode of action is crucial to make the assessment fitting for the
particular peptide under assessment
•Case-by-case assessments are needed, but difficult to harmonise(between
applicant and assessor and also in peer review between all member states and
EFSA)
•Alternative approaches to address data requirements may be needed
•Highly divergent properties of peptides –no one-size-fits-all approach possible
•Information on the mode of action is crucial to make the assessment fitting for the
particular peptide under assessment
•Case-by-case assessments are needed, but difficult to harmonise(between
applicant and assessor and also in peer review between all member states and
EFSA)
How tosolvethese issues?
•Notifier should provide all relevant information on mode of action and
particularities of the substance in PSM and in dossier
•Data waiving should be very well explained
•Way forward to harmonisecase-by-case approaches: problem formulation using
likelihood pathways (i.e., pathways to assess the likelihood of not meeting the
protection goal & generic analysis plans; Steenbergh et al., 2025)
•Notifier should provide all relevant information on mode of action and
particularities of the substance in PSM and in dossier
•Data waiving should be very well explained
•Way forward to harmonisecase-by-case approaches: problem formulation using
likelihood pathways (i.e., pathways to assess the likelihood of not meeting the
protection goal & generic analysis plans; Steenbergh et al., 2025)
As part of thegenericanalysis plans:
•Information on the toxicological relevance of breakdown products of
(poly)peptides/proteins
•Information on waivers for data requirements which may be inapplicable for
(poly)peptides/proteins (e.g., vapourpressure, IR/NMR-spectra, solubility in
organic solvents)
•Likelihoodpathways can be used to justify not performing a test by integrating all
information relevant for the assessment of a protection goal (such as hazard, e-fate,
effects)
•Information on the toxicological relevance of breakdown products of
(poly)peptides/proteins
•Information on waivers for data requirements which may be inapplicable for
(poly)peptides/proteins (e.g., vapourpressure, IR/NMR-spectra, solubility in
organic solvents)
•Likelihoodpathways can be used to justify not performing a test by integrating all
information relevant for the assessment of a protection goal (such as hazard, e-fate,
effects)
Furtherconsiderations
•In general, the most efficient way to produce proteins is by fermentation.
Assessment of the manufacturing process according to Part B-requirements (within
a dossier that is furthermore fully Part A) may be needed. This ‘crossover’ could be
better supported, most importantly by IUCLID.
•Antibodies may reach their full efficacy potential when applied as a mixture of
antibody types, each with a different binding site. In this light group registration
and simple procedures to expand the registration package could be valuable
options.
•Guidance on available conventions regarding the nomenclature of the various
peptide categories is helpful
•In general, the most efficient way to produce proteins is by fermentation.
Assessment of the manufacturing process according to Part B-requirements (within
a dossier that is furthermore fully Part A) may be needed. This ‘crossover’ could be
better supported, most importantly by IUCLID.
•Antibodies may reach their full efficacy potential when applied as a mixture of
antibody types, each with a different binding site. In this light group registration
and simple procedures to expand the registration package could be valuable
options.
•Guidance on available conventions regarding the nomenclature of the various
peptide categories is helpful
Conclusions
•Peptide-based plant protection products offer innovative, sustainable, and
specific alternatives to conventional chemicals
•Peptides can be assessed based on current Part A data requirements
•Clear communication lines between notifier and authority are important
to get a good understanding of what the active substance entails
•The problem formulation approach using likelihood pathways is a way
forward to harmonisethe case-by-case approaches needed for peptides
•Peptide-based plant protection products offer innovative, sustainable, and
specific alternatives to conventional chemicals
•Peptides can be assessed based on current Part A data requirements
•Clear communication lines between notifier and authority are important
to get a good understanding of what the active substance entails
•The problem formulation approach using likelihood pathways is a way
forward to harmonisethe case-by-case approaches needed for peptides
Unclassified / Non classifié
Restricted Use -À usage restreint
Canada’s Experience Regulating
Peptides as Pest Control Products
Human Health Considerations
Restricted Use -À usage restreint
Canada’s Experience Regulating
Peptides as Pest Control Products
Human Health Considerations
Unclassified / Non classifié
Restricted Use -À usage restreint
Peptide active ingredients registered in Canada
•BLAD polypeptide
•First registered in 2015
•Research authorization in 2016
•Three commercial end-use products (fungicide) on field and greenhouse food crops and ornamentals
•GS-omega/kappa-Hxtx-Hv1a peptide
•Research authorizations in 2017, 2018, 2019 and 2022
•Presubmissionconsultations in 2014, 2018 and 2019
•First registered in 2023
•Two commercial end-use products (insecticide/acaricide) on field and greenhouse food crops, cannabis, and ornamentals
•Flg22-Bt peptide
•Presubmissionconsultation in 2022
•Not yet registered; in public consultation phase
•Two commercial end-use products (fungicide) on soybean seed and wheat crops
•All peptides assessed under non-conventional framework
2
Restricted Use -À usage restreint
Peptide active ingredients registered in Canada
•BLAD polypeptide
•First registered in 2015
•Research authorization in 2016
•Three commercial end-use products (fungicide) on field and greenhouse food crops and ornamentals
•GS-omega/kappa-Hxtx-Hv1a peptide
•Research authorizations in 2017, 2018, 2019 and 2022
•Presubmissionconsultations in 2014, 2018 and 2019
•First registered in 2023
•Two commercial end-use products (insecticide/acaricide) on field and greenhouse food crops, cannabis, and ornamentals
•Flg22-Bt peptide
•Presubmissionconsultation in 2022
•Not yet registered; in public consultation phase
•Two commercial end-use products (fungicide) on soybean seed and wheat crops
•All peptides assessed under non-conventional framework
2
Unclassified / Non classifié
Restricted Use - À usage restreint
Non-conventional Tier I data requirements - Toxicology
3
Data code (DACO)
USEPA
guideline
number
Information requirement
Use patterns
Test substance
Food
Non-
foodTGAI/ISP EP
Tier I
Acute studies
4.2.1 4.6.1 870.1100 Acute oral R R TGAI/ISP EP
4.2.2 4.6.2 870.1200 Acute dermal CR CR TGAI/ISP EP
4.2.3 4.6.3 870.1300 Acute inhalation R R TGAI/ISP EP
4.2.4 4.6.4 870.2400 Primary eye irritation R R TGAI/ISP EP
4.2.5 4.6.5 870.2500 Primary dermal irritation R TGAI/ISP EP
4.2.6 4.6.6 870.2600 Dermal sensitization R R TGAI/ISP EP
4.2.9 4.6.8 None Other acute studies CR CR TGAI/ISP EP
Short-term studies
4.3.1 4.7.1 870.3100 Short-term oral (90 day rodent) R CR TGAI/ISP EP
4.3.2 4.7.2 870.3150 Short-term oral (90 day and/or 12 month dog) CR CR TGAI/ISP EP
4.3.4 4.7.3 870.3250 Short-term dermal (90 day rodent) CR CR TGAI/ISP EP
4.3.6 4.7.6 870.3465 Short-term inhalation (90 day rodent) CR CR TGAI/ISP EP
4.3.8 4.7.7 None Other short-term studies CR CR TGAI/ISP EP
Special studies
4.5.2 NR 870.3700 Prenatal developmental toxicity (rodent) R CR TGAI/ISP NR
4.5.4 NR 870.5100 Genotoxicity: Bacterial Reverse mutation assay R CR TGAI/ISP NR
4.5.5 NR 870.5300 Genotoxicity: In vitro mammalian cell assay R CR TGAI/ISP NR
4.8 4.8 None Other studies/Data/Reports CR CR TGAI/ISP EP
R = Required; CR = Conditionally required; NR = Not required; TGAI = Technical grade of active ingredient; ISP = Integrated system product; EP = End-use product
Restricted Use - À usage restreint
Non-conventional Tier I data requirements - Toxicology
3
Data code (DACO)
USEPA
guideline
number
Information requirement
Use patterns
Test substance
Food
Non-
foodTGAI/ISP EP
Tier I
Acute studies
4.2.1 4.6.1 870.1100 Acute oral R R TGAI/ISP EP
4.2.2 4.6.2 870.1200 Acute dermal CR CR TGAI/ISP EP
4.2.3 4.6.3 870.1300 Acute inhalation R R TGAI/ISP EP
4.2.4 4.6.4 870.2400 Primary eye irritation R R TGAI/ISP EP
4.2.5 4.6.5 870.2500 Primary dermal irritation R TGAI/ISP EP
4.2.6 4.6.6 870.2600 Dermal sensitization R R TGAI/ISP EP
4.2.9 4.6.8 None Other acute studies CR CR TGAI/ISP EP
Short-term studies
4.3.1 4.7.1 870.3100 Short-term oral (90 day rodent) R CR TGAI/ISP EP
4.3.2 4.7.2 870.3150 Short-term oral (90 day and/or 12 month dog) CR CR TGAI/ISP EP
4.3.4 4.7.3 870.3250 Short-term dermal (90 day rodent) CR CR TGAI/ISP EP
4.3.6 4.7.6 870.3465 Short-term inhalation (90 day rodent) CR CR TGAI/ISP EP
4.3.8 4.7.7 None Other short-term studies CR CR TGAI/ISP EP
Special studies
4.5.2 NR 870.3700 Prenatal developmental toxicity (rodent) R CR TGAI/ISP NR
4.5.4 NR 870.5100 Genotoxicity: Bacterial Reverse mutation assay R CR TGAI/ISP NR
4.5.5 NR 870.5300 Genotoxicity: In vitro mammalian cell assay R CR TGAI/ISP NR
4.8 4.8 None Other studies/Data/Reports CR CR TGAI/ISP EP
R = Required; CR = Conditionally required; NR = Not required; TGAI = Technical grade of active ingredient; ISP = Integrated system product; EP = End-use product
Unclassified / Non classifié
Restricted Use - À usage restreint
Considerations for BLAD polypeptide
•BLAD: 20 kDa polypeptide of β-conglutin or fragment of the amino acid sequence of β-conglutin
–fragment of naturally occurring seed storage protein in sweet lupine (Lupinus albus)
–purified from lupine seeds
•Mode of action (fungicide): damages fungal cell wall and disrupts inner cell membrane by binding and degrading chitin
•Tier I data requirements fulfilled with combination of guideline and non-guideline studies, information, and other data
•Acute 6-pack: low toxicity by oral, dermal, and inhalation routes, mildly irritating to skin and eyes, not a dermal sensitizer.
•Rationales accepted to waive repeat-dose toxicity, developmental toxicity, and genotoxicity studies
–limited potential for short term oral exposure (rapid biodegradability in the environment, polypeptides are generally hydrolyzed and
absorbed as amino acids on ingestion) and no quantifiable residues on treated crops
–low dermal absorption anticipated (large MW)
•Allergenicity addressed by:
–Bioinformatics, susceptibility to protease digestion, and low estimated dietary intake
–scientific literature review regarding potential allergenicity and cross-reactivity of BLAD polypeptide
–Serology study: low cross-reactivity in individuals sensitive to lupine and/or other legumes (e.g. peanuts, soy)
–Quality control procedures required to ensure that lupine seed proteins (conglutins) responsible for allergic reactions in sensitive
individuals are not present in Technical or end-use product
4
Restricted Use - À usage restreint
Considerations for BLAD polypeptide
•BLAD: 20 kDa polypeptide of β-conglutin or fragment of the amino acid sequence of β-conglutin
–fragment of naturally occurring seed storage protein in sweet lupine (Lupinus albus)
–purified from lupine seeds
•Mode of action (fungicide): damages fungal cell wall and disrupts inner cell membrane by binding and degrading chitin
•Tier I data requirements fulfilled with combination of guideline and non-guideline studies, information, and other data
•Acute 6-pack: low toxicity by oral, dermal, and inhalation routes, mildly irritating to skin and eyes, not a dermal sensitizer.
•Rationales accepted to waive repeat-dose toxicity, developmental toxicity, and genotoxicity studies
–limited potential for short term oral exposure (rapid biodegradability in the environment, polypeptides are generally hydrolyzed and
absorbed as amino acids on ingestion) and no quantifiable residues on treated crops
–low dermal absorption anticipated (large MW)
•Allergenicity addressed by:
–Bioinformatics, susceptibility to protease digestion, and low estimated dietary intake
–scientific literature review regarding potential allergenicity and cross-reactivity of BLAD polypeptide
–Serology study: low cross-reactivity in individuals sensitive to lupine and/or other legumes (e.g. peanuts, soy)
–Quality control procedures required to ensure that lupine seed proteins (conglutins) responsible for allergic reactions in sensitive
individuals are not present in Technical or end-use product
4
Unclassified / Non classifié
Restricted Use - À usage restreint
Considerations for GS-omega/kappa-Hxtx-Hv1a peptide
•4.565 kDa (22 amino acid) peptide, originally derived from venom of various Australian spider species
•Mode of action (insecticide/acaricide): reaches target sites in insect nervous system by diffusing into
hemocoel via spiracles; specific to ion channels and nicotinic acetylcholine receptors in insect nervous
system
•The peptide is expressed in genetically modified yeast strain and purified
–Additional microbial data requirements for product characterization due to manufacturing method
•Tier I data requirements fulfilled with guideline studies
–Acute 6-pack: low toxicity by oral, dermal, and inhalation routes, minimally irritating to the eyes, mildly irritating
to the skin, not a dermal sensitizer.
–90-day toxicity study (oral gavage in rats): treatment-related effects on serum chemistry and thyroid hormone
parameters observed at 500 mg a.i./kg/day (NOAEL = 125 mg a.i./kg/day)
–Prenatal developmental toxicity study (oral gavage in rats): Maternal and developmental NOAEL >719.8 mg
a.i./kg/day.
5
Restricted Use - À usage restreint
Considerations for GS-omega/kappa-Hxtx-Hv1a peptide
•4.565 kDa (22 amino acid) peptide, originally derived from venom of various Australian spider species
•Mode of action (insecticide/acaricide): reaches target sites in insect nervous system by diffusing into
hemocoel via spiracles; specific to ion channels and nicotinic acetylcholine receptors in insect nervous
system
•The peptide is expressed in genetically modified yeast strain and purified
–Additional microbial data requirements for product characterization due to manufacturing method
•Tier I data requirements fulfilled with guideline studies
–Acute 6-pack: low toxicity by oral, dermal, and inhalation routes, minimally irritating to the eyes, mildly irritating
to the skin, not a dermal sensitizer.
–90-day toxicity study (oral gavage in rats): treatment-related effects on serum chemistry and thyroid hormone
parameters observed at 500 mg a.i./kg/day (NOAEL = 125 mg a.i./kg/day)
–Prenatal developmental toxicity study (oral gavage in rats): Maternal and developmental NOAEL >719.8 mg
a.i./kg/day.
5
Unclassified / Non classifié
Restricted Use - À usage restreint
Considerations for Flg22-Bt peptide
•22 amino acid peptide; synthetic analog of a flagellin protein from Bacillus thuringiensis.
•Mode of action (fungicide): broad-spectrum stimulator of the plant immune response to provide
preventative protection against fungal plant disease.
•Peptide is manufactured synthetically
•Tier I data requirements fulfilled with combination of guideline and non-guideline studies,
information, and other data
–Acute 6-pack: low acute toxicity by oral and dermal routes, slightly acutely toxic by inhalation, non-
irritating to eyes and skin, not a dermal sensitizer
–Not mutagenic in a reverse gene mutation assay in bacteria, nor in an in vitro mammalian cell gene
mutation assay
–Rationales accepted to waive repeat-dose toxicity studies accepted based on in vitro digestion study and
allergenicity analyses
6
Restricted Use - À usage restreint
Considerations for Flg22-Bt peptide
•22 amino acid peptide; synthetic analog of a flagellin protein from Bacillus thuringiensis.
•Mode of action (fungicide): broad-spectrum stimulator of the plant immune response to provide
preventative protection against fungal plant disease.
•Peptide is manufactured synthetically
•Tier I data requirements fulfilled with combination of guideline and non-guideline studies,
information, and other data
–Acute 6-pack: low acute toxicity by oral and dermal routes, slightly acutely toxic by inhalation, non-
irritating to eyes and skin, not a dermal sensitizer
–Not mutagenic in a reverse gene mutation assay in bacteria, nor in an in vitro mammalian cell gene
mutation assay
–Rationales accepted to waive repeat-dose toxicity studies accepted based on in vitro digestion study and
allergenicity analyses
6
Unclassified / Non classifié
Restricted Use - À usage restreint
Additional information
•PMRA’sGuidance for the Registration of Non-Conventional Pest Control Products describes the data requirements for
active ingredients which meet the definition of non-conventional pest control products.
•For more details on the assessments of these peptide active ingredients, refer to the Proposed Registration Documents
(PRDs):
•BLAD polypeptide: PRD2015-01 and PRD2019-02
•GS-omega/kappa-Hxtx-Hv1a peptide: PRD2023-02
•Flg22-Bt peptide: PRD2025-01
7
Restricted Use - À usage restreint
Additional information
•PMRA’sGuidance for the Registration of Non-Conventional Pest Control Products describes the data requirements for
active ingredients which meet the definition of non-conventional pest control products.
•For more details on the assessments of these peptide active ingredients, refer to the Proposed Registration Documents
(PRDs):
•BLAD polypeptide: PRD2015-01 and PRD2019-02
•GS-omega/kappa-Hxtx-Hv1a peptide: PRD2023-02
•Flg22-Bt peptide: PRD2025-01
7
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