RNA Product Vision

1. RNA Product Vision NEB International Subsidiary GMs visit 11 July 2012 Brett Robb robb@neb.com Breton Hornblowerhornblower@neb.com

2. Goals for today • To have a conversation, informed by Research and Marketing, about NEB’s potential in various sectors of the RNA market place • Where we are relative to the market? • Where do we think the market will go? • Our vision for NEB’s RNA product landscape • Short, Medium, Long term • Risks, challenges, and region specific considerations

3. Agenda • RNA market analysis • Current revenue • Customer segments by application • Market attractiveness grid • Current and proposed RNA product portfolio • RNA Synthesis • cDNA Synthesis and RT-PCR • Modifying enzymes for RNA analysis • Summary

4. RNA Product Line 2011 Yearly Sales 20% Growth Rolling 12 Months

5. RNA Market Segments • RNA Isolation & Purification • We define this to include enrichment and capture of RNA in current sales data • RNA Synthesis • RNA Synthesis as a Service • RNA Modification Enzymes • RNA Sequencing • cDNA Synthesis and RT PCR • Real-Time PCR

6. Quarterly Growth by Product Line

7. Market Attractiveness Grid Market Attractiveness NEB’s Business Strength • Market Size • Annual growth rate • Historical profit margin • Competitive intensity • Current market share • Annual share growth rate • Brand reputation • Research & Product Capabilities and Capacity • IP position • Channel to market/Promotional effectiveness ~1 year range

8. Product Development: Applying the Market Attractiveness Grid Market Attractiveness NEB’s Business Strength

9. RNA Market Attractiveness Grid

10. RNA Market Attractiveness Grid 100M 50M 200M 430M 70M 31M 216M

11. RNA Market Attractiveness Grid 100M 50M 200M 430M 70M 31M 216M NEB’s current market share (4.1M)

12. RNA Synthesis is making RNA in vitro • Why? • RNA structure and function studies • Hybridization studies • Ribozyme biochemistry • Antisense or RNAi • Microarrays • Microinjection/transfection • Stem cells/cell fate • Stemgent, Moderna, Factor Biosciences • Translation • RNA vaccines • Novartis • CureVac • Argos • BioNTech

13. In Vitro RNA Synthesis dsDNATemplate T7 Promoter T7 Pol RNaseInhibitor IPP NTPs mGpppNm AAAAAAAN mGpppNm AAAAAAAN mGpppNm AAAAAAAN mGpppNm AAAAAAAN DNase, Antarctic Pase Clean up Italics indicate product missing from NEB line Many applications

14. RNA Synthesis – example workflow

15. RNA Synthesis Business

16. RNA Synthesis - Competition OTC Bulk Service

17. RNA synthesis

18. RNA synthesis – recommendations • OTC • Easier and specialized kits including ARCA and modified NTPs • Sales/manufacturing modified nucleosides • Bulks • Sales/manufacturing modified nucleosides • Manufacture of hRNasin in house • Service • IP and Legal review • Create pricing structure and contract frameworks • Sales/manufacturing modified nucleosides • RNA Purification techniques • Regulatory • QC

19. RNA Market Attractiveness Grid 100M 50M 200M 430M 70M 31M 216M NEB’s current market share (4.1M)

20. cDNA Synthesis and RT-PCR • Why? • Gene expression analysis • Upstream of qPCR • In microarray workflows • Upstream of end-point PCR • In RNA seq workflows • Gene cloning Competition And many others

21. Reverse Transcription– example workflow Short-term Medium-term Long-term

22. cDNA synthesis and RT-PCR

23. Reverse Transcription – Recommendations • Immediate goals: • Consolidate current RT PCR kits • Develop 1st strand kit for M-MuLV RNase H- • Mid-term goals: • Develop one-step RT-PCR kits • Longer term: • Solidify RT goals • Coordinate efforts – NEB Inc., NEB SH, LeGene • Access real-time PCR capability

24. RNA Market Attractiveness Grid 100M 50M 200M 430M 70M 31M 216M NEB’s current market share (4.1M)

25. RNA Modification Enzymes– Where do they fit? RNA modifying enzymes expand the capabilities of current RNA Seq and other analyses

26. RNAlibrary construction for Illumina mRNA Small RNA

27. RNA Modifying Enzymes – current lineup Existing Products • Ligation • T4 Rnl1 • T4 Rnl2 • T4 Rnl2tr • T4 Rnl2tr K227Q • Adenylated DNA linker • Labeling and modification • Hen1 • PNK • CIP • AntP • Selective modification • 5’-Deadenlyase • Selective Nucleases • XRN-1 • RNase H • RNase HII • Exonuclease T Recent releases • Ligation • T4 Rnl2tr K227Q – M0351S/L • Lowest possible background for linker attachment • DNA 5’-Adenylation kit – E2610S • Make pre-adenylated cloning linkers of any sequence • Labeling and modification • mRNA Capping • Selective modification • RNA 5’-Pyrophosphohydrolase (RppH) – M0356 • Removes PP from PPP-RNA Competition

28. RNA modifying enzymes as tools that expand the capability of RNA analysis • Looking forward, RNA Seq will be used to ask increasingly refined questions in RNA research. This will require tools to: • Selectively capture some RNA species from a mixed population • mRNAs with modified bases • Capped mRNAs • Selectively represent some RNA species but not others in RNA Seq libraries • Selectively generate ligatable RNA ends • Selectively remove some RNAs • Nucleases • Affinity pullouts mono-phosphate di-phosphate tri-phosphate

29. Reagents for RNA analysis – future products Short term Medium term Long term

30. RNA Modifying Enzymes

31. RNA Modifying Enzymes– recommendations • Short-term development of new ligases and incorporation into NGS workflows • Further differentiate our NGS LC reagents • Additional resources in Research and Applications Development to drive early and mid-stage development of medium and long product development goals

32. RNA analysis – longer term • Be first to market with next-generation RNA analysis technology • Position ourselves as the go-to company for RNA enzymes to fuel new technology platforms • Anticipate the needs of RNA researchers

33. Who? Current Additional Needed

34. Summary • RNA revenue is small but rapidly growing portion of total NEB revenue. • Current opportunity pipeline includes ‘needle moving’ deals. • Novartis • Shire • Market attractiveness analysis guides focus toward: • cDNA synthesis and RT-PCR • RNA modifying enzymes to enable RNA Seq • RNA synthesis reagents and RNA synthesis as a service • Bringing the proposed product portfolio to market in a timely fashion requires additional or reallocation of resources across all departments.