1. Page 1© 2014 Oxitec Limited Oxitec Insect Control for public health and agriculture BVL –Symposium 5-6 Nov 2014 Berlin Camilla Beech

2. Page 2© 2014 Oxitec Limited Combat insect- borne diseases Improve crop yields through the reduction of pest insect populations biological approach that is safe, sustainable, economic and applicable to many insect species worldwide Oxitec insect control technology

3. Page 3© 2014 Oxitec Limited New control solutions needed for public health and agriculture consumer demand for more food on less land demand for residue reduction changing pest pressures fewer available pesticides pesticide resistance Why engineer insects for pest control ?

4. Page 4© 2014 Oxitec Limited Oxitec introduces two genes Self Limiting Gene Repressed with an antidote during male insect production Passed on to progeny fathered by Oxitec males Prevents offspring from developing into reproductive adults Without continued release disappears from the gene pool and environment Marker Gene Fluorescent Protein detected by special light Allows track and trace for Oxitec insects Allows estimation of pest population sizes Allows effective monitoring of pest population suppression Injecting genes into insect egg Self Limiting Gene Fluorescent Marker Gene

5. Page 5© 2014 Oxitec Limited Our approach Oxitec technology disrupts the reproductive cycle of pest insects

6. Page 6© 2014 Oxitec Limited Oxitec self limiting technology 1 st Generation population control Physical sorting males Effects male and female offspring, which fail to reach adulthood Genetic sorting to give males Effects only female offspring which fail to reach maturity 2 nd Generation Male selection Genetic sorting to give males Effects both males and female 3 nd Generation early population Control No effects on beneficial insects like bees Compatible with Crop Protection technology Oxitec technology is species specific

7. Page 7© 2014 Oxitec Limited Oxitec technology is species specific Cannot establish in the environment Males do not bite/ oviposit in crop Safety No adverse effects on predators/parasitoids tested Non-toxic proteins No allergenic homologies/epitopes Genetically stable

8. Page 8© 2014 Oxitec Limited Monitoring built in Released males seek females Genetic marker allows “track and trace in the environment” Released males seek females Genetic marker allows “track and trace in the environment” Releases monitored continually to adjust release rates

9. Page 9© 2014 Oxitec Limited Integration with other treatments  Insecticide treatment as an initial knock-down  On-going breeding site removal and or larvicides  Sustained, preventative genetic control  Spot treatments with insecticides Insecticides Time Pest population Oxitec solution Threshold Insecticides Time Oxitec solution Threshold Untreated

10. Page 10© 2014 Oxitec Limited TargetCrop Medfly Citrus/pome/ stone fruit Olive flyOlive Diamondback moth Brassica Pink bollworm Cotton SilkwormSilk TargetCrops Drosophila suzukii Soft fruit Red flour beetle Stored products Agriculture In development Oxitec portfolio TargetVector of Aedes aegyptiDengue Aedes albopictus Chikungunya & dengue Anopheles stephensi Malaria Public Health

11. Page 11© 2014 Oxitec Limited 96% 92% 99% 94% Every A. aegypti field trial showed greater than 90% mosquito suppression

12. Page 12© 2014 Oxitec Limited Benefits Oxitec’s mating-based pest control approach provides: Efficacy! Male-only releases Biological targeting Species-specific pest control Not toxic or allergenic Heritable visible marker Self-limiting in the environment

13. Page 13© 2014 Oxitec Limited The challenge:

14. Page 14© 2014 Oxitec Limited GM crops: GM insects GM cropsOxitec insects Genetic change to food productGenetic change to pest only Can persist in the environmentSelf-limiting Genes may pass to non-GM plantsGenes do not pass to other species Complex monitoringSimple monitoring

15. Page 15© 2014 Oxitec Limited Regulatory approach Disruptive innovation –Often no clear regulatory pathway –Currently using a mix of GM legislation (EU, Brazil) and product legislation (USA). –GM legislation (safety) followed by product legislation (label) –May hinder progress and use Proportionate pragmatic regulation needed –Risk/ benefit analysis key to decision making –Ideally a “ product “ registration including safety –Biological control may be a precedent ?

16. Page 16© 2014 Oxitec Limited Regulatory progress Across all Oxitec GM insects – all applications successful “ Environmentally preferable” USDA EIS Oxitec Aedes aegypti received approval for commercia l releases in Brazil April 2014 Import and contained trials approved Austria France Greece Guatemala Israel Singapore Thailand Vietnam UK Current applications for outdoor release India Spain Caribbean KSA Morocco Outdoor release approved Brazil Cayman Malaysia Mexico USA Panama

17. Page 17© 2014 Oxitec Limited Acknowledgements

18. Page 18© 2014 Oxitec Limited Thank you www.oxitec.com @Oxitec camilla.beech@oxitec.com