Benitec Biopharma Inc. · NASDAQ:BNTC

Benitec Biopharma — Technical Presentation (November 2018)

19 slides from Benitec Biopharma's technical presentation, Nov 11, 2018

1. Slide 1: Potent and durable RNAi mediated suppression of Hepatitis B Virus infection in a mouse model by CELID vector

   Potent and durable RNAi mediated suppression of Hepatitis B Virus infection in a mouse model by a non- viral Closed Ended Linear DNA (CELID) vector November 11, 2018 Dr. Peter W. Roelvink Senior Director Research Copyright © Benitec Biopharma Ltd www.benitec.com

2. Slide 2: Safe Harbor Statement

   Safe Harbor Statement This presentation contains "forward-looking statements" within the meaning of section 27A of the US Securities Act of 1933 and section 21E of the US Securities Exchange Act of 1934. Benitec has tried to identify such forward-looking statements by use of such words as "expects,"

3. Slide 3: Contributors

   Contributors Badriprasad Ananthanarayanan Mick Graham Tin Mao Vanessa Strings-Ufombah Shih-Chu Kao Kermit Zhang Peter Roelvink David Suhy Copyright © Benitec Biopharma Ltd 3 www.benitec.com

4. Slide 4: Positioning of shRNA Used in Clinical Construct Ensure Cleavage of Multiple HBV Transcripts

   Positioning of shRNA Used in Clinical Construct Ensure Cleavage of Multiple HBV Transcripts HBV proteins HBV genome HBV Transcripts shRNA 4 shRNA 8 shRNA 9 * Sequences selected for shRNA are well conserved across HBV genotypes A-H Copyright © Benitec Biopharma Ltd 4 www.benitec.com

5. Slide 5: BB-103: Triple shmiR anti HBV

   BB-103: Triple shmiR anti HBV ITR A B C ITR U69-shmiR-4 U61-shmiR-8 U68-shmiR-9 • Single stranded recombinant DNA • Wild type Pol III promoters for high expression • Model shRNA into miRNA backbone for safety • High fidelity: a few predominant, highly active species of siRNA • May help reduce potent

6. Slide 6: Overview of Phoenix Bio's PXB Human Liver Chimeric Mouse

   Overview of Phoenix Bio’s PXB Human Liver Chimeric Mouse Copyright © Benitec Biopharma Ltd 6 www.benitec.com

7. Slide 7: BB-103 Combo with Entecavir: Reduction of Serum HBV DNA Levels

   BB-103 Combo with Entecavir: Reduction of Serum HBV DNA Levels 1.0E+09 Untreated, HBV infected PXB mice 1.0E+08 Serum HBV DNA (copies/ml) 1.0E+07 1.34 log drop BB-103 (*max 2.17 Day 63) * * 1.0E+06 2.63 log drop ETV 1.0E+05 LLOQ – 4e4 DNA copies ml (~ 3.72 logs) (HBV detectable but not quantifiable)

8. Slide 8: BB-103 and Entecavir as Monotherapy: Reduction of Serum HBsAg Levels

   BB-103 and Entecavir as Monotherapy: Reduction of Serum HBsAg (S-Antigen) Levels 1.0E+04 Untreated, HBV infected PXB mice 1.0E+03 0.46 log drop ETV Serum HBs Ag (IU/ml) 1.0E+02 1.49 log drop BB-103 (*max 1.94 Day 70) 1.0E+01 Entecavir (ETV) administered daily 0 7 14 21 28 35 42 49 56 63 70 77 84 91

9. Slide 9: Problems with AAV Delivery

   Problems with AAV Delivery Complex Manufacturing in mammalian or insect cells Pre-existing antibodies in patients against AAV serotypes prevents administration of an AAV vector Administration of an AAV vector prevents repeat dosing Solution (perhaps): Celids Copyright © Benitec Biopharma Ltd 9 www.b

10. Slide 10: What is a Celid?

    What is a Celid? It’s a Closed Ended Linear DNA and to be more precise: It looks like the genome of an AAV minus the capsid, but is not size restricted and thus can be much shorter than 4.6 Kb A B C U69-shmiR-4 U61-shmiR-8 U68-shmiR-9 Copyright © Benitec Biopharma Ltd 10 www.benitec.com

11. Slide 11: Production of Celids

    Production of Celids Celids are produced by infection of insect cells by two baculoviruses. One carries the Celid, the other carries the Replication genes of an AAV but NOT the capsid genes. This results in production of Celids that can be purified from harvested insect cells using DNA purification

12. Slide 12: Long term expression of luc-Celid in vivo

    Long term expression of luc-Celid in vivo Luciferase expression Luciferase expression 1010 10 9 109 Radiance (photons/s/cm^2/sr) 10 8 Radiance (photons/s/cm2/sr) 108 10 7 CELiD 451 CELiD 452 CELiD 453 107 CELiD 454 10 6 CELiD 455 106 CELiD CELiD 456 CELiD 457 10 5 CELiD 458 105 Plasmid CELiD 459 CEL

13. Slide 13: Characterizing Celids

    Characterizing Celids  Fully characterized CEliD 286 (HBV triple shmiR) - Purified (glycerol gradients) - Mapped 120.0 - Sequenced - Activity % inhibition of Luc reporter 100.0 80.0 60.0 40.0 20.0 0.0 cBL286 pBL283 single shmiR All4 71.5 62.4 71.0 sh8 80.6 80.9 96.8 All9 82.4 70.7 97.5 Copyright ©

14. Slide 14: In Vivo Evaluation of Celid Activity

    In Vivo Evaluation of Celid Activity HBV Hydro Dynamic Injection study in NOD-SCID mice WUXI study 20170123A Copyright © Benitec Biopharma Ltd 14 www.benitec.com

15. Slide 15: In Vivo Evaluation of Celid Activity: set up

    In Vivo Evaluation of Celid Activity: set up Test groups: Saline + HepB plasmid (Group D) TT035 + HepB plasmid (negative control that produces 3 anti- HepC shmiRs) Celid (produces 3 anti-HBV shmiRs) + HepB plasmid HDI of 10 ug in volume of 8% of mouse bodyweight/5 seconds HepB DNA levels determined

16. Slide 16: Serum HBV DNA

    Serum HBV DNA Copyright © Benitec Biopharma Ltd 16 www.benitec.com

17. Slide 17: Serum HBsAg

    Serum HBsAg Copyright © Benitec Biopharma Ltd 17 www.benitec.com

18. Slide 18: Serum HBeAg

    Serum HBeAg Copyright © Benitec Biopharma Ltd 18 www.benitec.com

19. Slide 19: Conclusions

    Conclusions The NOD-SCID HDI mouse model appears suitable for quick evaluation/ranking of potential anti HepB therapeutics. The model is not necessarily suitable for long term (i.e. over 30 days p.i.) evaluation. Celids are molecular therapeutic tools that have utility in a preclinical setting. Copy

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