Biotron Limited · ASX:BIT

Biotron — 7th International AIDS Society (IAS) Conference 2013

15 slides from Biotron's conference presentation, Jul 1, 2013

1. Slide 1: Presentation of HIV Trial Data at International AIDS Society Conference

   Level 2, 66 Hunter Street Sydney NSW 2000 Tel: (61-2) 9300 3344 Fax: (61-2) 9221 6333 E-mail: pnightingale@biotron.com.au Website: www.biotron.com.au For personal use only 1 July 2013 The Manager Companies ASX Limited 20 Bridge Street Sydney NSW 2000 (15 pages by email) Dear Madam PRESENTATION OF HI

2. Slide 2: Trial results continued and About Biotron and BIT225

   The most pronounced antiviral effect was noted in trial participants with the highest viral loads. Their cells demonstrated a statistically significant and up to a three-fold reduction in virus. The results are important as they suggest that BIT225 has the potential to be included in future HIV elim

3. Slide 3: BIT225, a Novel Inhibitor of HIV-1 Release from HIV-1 Reservoirs of the Myeloid Lineage

   BIT225, a Novel Inhibitor of HIV-1 Release from HIV-1 Reservoirs of the Myeloid Lineage John Wilkinson*1, Carolyn Luscombe1, Gary Ewart1, Stephen Kerr2, Nattaya Tanliang3, Winai Ratanasuwan3, Robert Murphy4, and Michelle Miller1 1Biotron Limited, Sydney, Australia 2HIV-NAT, Bangkok, Thailand 3Sirira

4. Slide 4: BIT225, a Novel Inhibitor of HIV-1 Release from HIV-1 Reservoirs of the Myeloid Lineage

   For personal use only BIT225, a Novel Inhibitor of HIV-­‐1 Release from HIV-­‐1 Reservoirs of the Myeloid Lineage -­‐ John Wilkinson -­‐ Biotron Limited, Australia IAS 2013 Towards an HIV Cure Symposium

5. Slide 5: BIT225

   BIT225 (N-­‐[5-­‐(1-­‐Methyl-­‐1H-­‐pyrazol-­‐4-­‐yl)-­‐napthalene-­‐2-­‐ carbonyl]-­‐guanidine) • First-­‐in-­‐class drug targeHng HIV-­‐1 within cells of the myeloid lineage (selected For personal use only as lead from ~250 compound library designed to target Vpu) • AnH-­‐HIV-­‐1 acHvity in primar

6. Slide 6: Significant HIV-1 Reduction in Human Macrophages in vitro with BIT225

   Significant HIV-­‐1 ReducHon in Human Macrophages in vitro with BIT225 For personal use only Chronic Kinetics d14 infection & d21 BIT225 addition 200 HIV-1 Replication RT 150 DMSO Control BIT225 100 +BIT225 50 16 17 19 21 22 23 24 25 26 27 28 Time (days) +HIV-1 Khoury et al., An7microbial Agents and

7. Slide 7: Monocytes and HIV-1 Infection

   Monocytes and HIV-­‐1 InfecHon For personal use only • CD14+ monocytes (~30%) are long lived cells with reports that once infected they can disseminate virus for 6 weeks in vitro (Sharova et al EMBO J 2005) • The minor CD16+ subset (5-­‐10% of monocytes) are preferenHally infected; higher CCR5 level

8. Slide 8: A Phase 1b/2a Trial with BIT225

   A Phase 1b/2a Trial with BIT225 For personal use only BIT225-­‐004, a Phase 1b/2a, Placebo-­‐Controlled, Randomised Study of the Safety, Pharmacokine7cs and An7viral Ac7vity of BIT225 in Pa7ents with Human Immunodeficiency Virus-­‐1 Infec7on Robert Murphy, Winai Ratanasuwan and Ruengpung SuIhent ACLI

9. Slide 9: BIT225-004: Synopsis

   BIT225-­‐004: Synopsis For personal use only Primary objec7ve The safety and tolerability of 400 mg of BIT225 BID compared with placebo in paHents with HIV-­‐1 infecHon that are anHretroviral therapy naïve Secondary objec7ves • The pharmacokineHcs of 400 mg of BIT225 administered daily on day 1 & 10

10. Slide 10: BIT225 Antiviral Activity in a Clinical Setting

    BIT225 AnHviral AcHvity in a Clinical Sepng In a study of only 10 days with a drug targeHng cells of the myeloid lineage, For personal use only dramaHc decreases in HIV-­‐1 viral load and concomitant increases in CD4+ T cell number are unlikely to be observed. Issues with access to macrophages Aim:

11. Slide 11: Monocyte Co-Culture Assay

    Monocyte Co-­‐Culture Assay use only Placebo (n=7) BIT225 Treated (n=12) 16 16 HIV-­‐1 ReplicaHon (pg/200uL) Day 0 Bleed 14 14 Day 5 Bleed Day 10 Bleed 12 12 Day 20 Bleed For personal 10 10 8 8 6 6 4 4 2 2 5 10 15 20 25 5 10 15 20 25 Time in Co-­‐culture (days)

12. Slide 12: Monocyte Co-Culture Assay: High Viral Load

    Monocyte Co-­‐Culture Assay BIT225 Treated: High Viral Load n=6 For personal use only 16 14 Day 0 Bleed HIV-­‐1 ReplicaHon (pg/200uL) Day 5 Bleed 12 Day 10 Bleed Day 20 Bleed 10 8 6 4 2 5 10 15 20 25 Time in Co-­‐culture (days) Mann-­‐Whitney p= 0 v 5 0.25 0.09 0.1 0.05 0.04 0.2 0 v 10 0.25 0.31 0.3

13. Slide 13: Monocyte Co-Culture Assay: Low Viral Load

    Monocyte Co-­‐Culture Assay BIT225 Treated: Low Viral Load n=6 For personal use only 16 14 HIV-­‐1 ReplicaHon (pg/200uL) 12 Day 0 Bleed 10 Day 5 Bleed Day 10 Bleed 8 Day 20 Bleed 6 4 2 5 10 15 20 25 Time in co-culture (days)

14. Slide 14: In Summary

    In Summary For personal use only • This study strengthens our previous findings in vitro and ex vivo, supporHng the role for BIT225 as a novel drug targeHng HIV-­‐1 within the myeloid compartment • In those paHents with high HIV-­‐1+ viral loads, treatment with BIT225 for 10 days significantly reduced

15. Slide 15: Acknowledgements

    Acknowledgements For personal use only Biotron Limited ACLIRES Dr Michelle Miller Prof Rob Murphy Dr Carolyn Luscombe Dr Sven-­‐Iver Lorenzen Dr Gary Ewart Audrey Thomson Siriraj Hospital Bronwyn Williams Trial ParHcipants Craig Witherington A/Prof Winai Ratanasuwan Gabriela Khoury Prof Ruengpung Su

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