BIOTRON LIMITED (ASX:BIT) Biotech Showcase Room Mission II - - PowerPoint PPT Presentation

BIOTRON LIMITED (ASX:BIT) Biotech Showcase Room Mission II Tuesday, 14 Jan 2014

Forward Looking Statements

This presentation may contain forward‐looking statements with respect to the financial condition, results and business achievements/performance of Biotron Limited and certain of the plans and

• bjectives of its management. These statements are statements that are not historical facts. Words

such as “should”, “expects”, “anticipates”, “estimates”, “believes” or similar expressions, as they relate to Biotron Limited, are intended to identify forward‐looking statements. By their nature, forward‐looking statements involve risk and uncertainty because they reflect Biotron’s current expectations and assumptions as to future events and circumstances that may not prove accurate. There is no guarantee that the expected events, trends or results will actually occur. Any changes in such assumptions or expectations could cause actual results to differ materially from current expectations.

Biotron Limited Overview

• Clinical stage antiviral drug development company
• Clinical programs for Hepatitis C virus (HCV) and HIV
• Earlier stage programs include Dengue and others
• Headquartered in Sydney, Australia
• IPO Jan 2001 (ASX:BIT)
• Key recent highlights
• Nov 2013 – Commenced Phase 2, HCV gen 1 & 3, 3-month dosing trial
• Oct 2013 – HIV/HCV: Announced positive preliminary HCV gen 3 data from Phase 2 trial
• June 2013 – HIV: Announced positive results from Phase 2a trial
• Nov 2012 – HCV: Announced positive 48-week follow-up data from Phase 2a trial

Biotron - Advanced Pipeline of Clinical Programs

INDICATION VIRAL TARGET DISCOVERY PRECLINICAL PHASE 1a PHASE 1b PHASE 2a PHASE 2b STATUS Hep C p7

• Ph 2a complete;
• Ph 2b (3 mth dosing)

in progress

HIV Vpu

• Ph 2a complete

HIV/Hep C Vpu/p7

• Ph 2 completed

clinical phase

Next generation - HCV p7

• Ready for IND-

enabling (formal preclinical) studies

Dengue M

Hepatitis C Virus – The Silent Killer

• 180 m people infected worldwide (3% world population)
• 130 m are chronically infected;
• 4 m patients in US (2.7 m chronically infected)
• Majority of infected patients remain untreated or untreatable
• Standard of care is pegylated interferon and ribavirin (PEG/RBV)
• Up to 50% patients don’t respond to PEG/RBV
• Significant side effect profile – high drop out rate
• Documented need for new, safer, direct-acting antiviral (DAA) drugs
• HCV therapeutic space has seen rapid progress over last +2 years

Hepatitis C Virus – Recent Advancements

• Industry focus on developing direct-acting antiviral (DAA) treatments that are:
• Safe (no PEG/RBV)
• Highly effective against all genotypes
• Convenient (i.e. oral)
• Shorter treatment duration (ideally 4 – 6 weeks)
• Cost effective
• Treatment of HCV requires more than one different classes of drugs to prevent resistance
• Sofosbuvir (SOF)/Sovaldi (Gilead) and Simeprevir/Olysio (Janssen) received FDA approval in

late 2013

• Several other polymerase and protease inhibitors, singly and in combination, also in

development

Hepatitis C Virus – Recent Advancements

• BUT these new treatments don’t cover everything on the wish-list i.e.
• Not equally effective against ALL genotypes
• Still require RBV for maximal effect
• 12 weeks minimum treatment (24 weeks for gen 3)
• High cost (SOF expected to cost $84,000 for 12 weeks course)
• There is still a need for additional drugs for new combinations:
• To target all genotypes
• To remove RBV
• To shorten treatment period
• Reduce costs
• We’re at the start of the new world of DAAs, not the end
• Likely to be multiple treatment regimens to cover spectrum of HCV disease

Hepatitis C Virus – Market Opportunity

Upper-middle Source: Evolving epidemiology of hepatitis C virus (Clin Microbiol Infect. 2011; 17(2): 107-115). Income classification from The World Bank, 2013.

Points to note:

• USA and Europe

represent major markets but other, larger markets are emerging.

• IFN/RBV likely to remain

central to treatment in these other countries due to costs

• Add-ons to IFN/RBV in

these countries may shorten treatment times and improve

• utcomes

BIT225 – New Class of HCV DAA Drug

 Novel, oral, small molecule compound  Only one of its class (p7 inhibitor) in clinical trials  Inhibits viral assembly; active at later stage of virus life cycle to polymerase and protease inhibitors  Doesn’t readily generate resistance  Pan-genotype activity:  Clinically active against hard-to-treat HCV genotype 1 (1a and 1b) and genotype 3  Active in vitro against other main genotypes  Also active against HIV hiding in reservoir cells

ENTRY INHIBITORS POLYMERASE/PROTEASE INHIBITORS e.g. Sofosbuvir/Simeprevir

BIT225 - ASSEMBLY/BUDDING INHIBITOR

BIT225 – Proven Clinical Activity Against HCV

Treatment 12 WEEKS Early Virological Response* 48 WEEKS Sustained Virological Response* 400 mg BIT225 + IFN/RBV 86% 100% 200 mg BIT225 + IFN/RBV 88% 88% Placebo + IFN/RBV 63% 75% *virus levels below limit of detection i.e. 50 IU/ml

4 wks 12 wks 48 wks Interferon + Ribavirin Placebo BIT225 Clear demonstration that BIT225 has good antiviral activity in hard-to-treat, treatment-naïve HCV genotype 1 (a and b) patients

BIT225-005

HCV Phase 2 Three-Month Dosing Trial BIT225-008

4 wks 12 wks 24 wks 48 wks (end for Gen 3) (end for Gen 1) Placebo BIT225 Interferon + Ribavirin

• Randomised, placebo-controlled, double-blind trial
• Treatment naïve, HCV gen 1 and 3
• 3 months dosing with BIT225 in combination with IFN/RBV
• Using new capsule formulation
• In progress; expect to complete recruitment mid-2014

AIMS:

• Demonstrate safety of BIT225 with 3 months dosing
• Extend efficacy data to HCV gen 3
• Set BIT225 up for partnering with other DAA classes

HIV/HCV Co-infected Population

• One third of HIV-positives are also infected with HCV
• Rapid progression to liver failure
• Respond poorly to IFN/RBV
• ~ 19% SVR rate
• Often an after-thought in trials of new DAAs
• Drug-drug interactions limits use of protease inhibitors (i.e. Boceprevir,

Telaprevir and Simeprevir) in these patients

• Limited classes of new DAAs to combine with SOF in this population

BIT225 – HIV / HCV Co-Infected Trial (BIT225-006)

• Phase 2 HIV/HCV trial - completed clinical phase in July 2013

– Genotypes 1 and 3; 28 days dosing in combination with IFN/RBV – Treatment-naïve to HCV treatment with RBV and/or IFN; HIV controlled by antiretroviral drugs (ART) – Interim 12-week gen 3 data presented at AASLD conference in Washington DC in Oct ‘13

0 1 wks 5 wks 48 wks

ART Interferon + Ribavirin BIT225

BIT225 – HIV / HCV gen 3 - Proven Efficacy

• 6
• 5
• 4
• 3
• 2
• 1

1 7 14 21 28 35 42 49 56 63 70 77 84 HCV RNA (Baseline adjusted log10 change) Time of Sample (Day)

HCV RNA Change from baseline - G3

603 - GT3a 602 - GT3a 606 - GT3a 607 - GT3a 609 - GT3a 610 - GT3a 611 - GT3a 612 - GT3-

BIT225

LLQ

• At 12 weeks - All HCV genotype 3

patients who completed treatment were clear of virus

• Rate of decline in virus levels increased

after addition of BIT225 at day 7

• Data demonstrates that:
• BIT225 is active in gen 3
• BIT225 improves outcome for hard-

to-treat HIV/HCV co-infected patients

BIT225 is uniquely placed due to dual anti-HIV and anti–HCV activity

HIV – Towards a Cure

• 34 million people worldwide living with HIV
• Market (US and Europe) is currently US$13.36

billion p.a.

• Market expected to expand to US$20 billion by

2016

• New drugs have improved the quality of life for

HIV patients and prevented the virus from developing into AIDS.

• Once on treatment, patients need to keep on

taking the drugs to keep virus levels under control

• Industry is now focused on developing drugs to

eradicate or cure HIV infection

BIT225 and HIV

• BIT225 has potent anti-HIV activity

– Targets Vpu protein of HIV

• Similar class of protein to HCV p7

– Unique mode of action targets HIV “hiding” in long-lived macrophage reservoir cells

• Reservoirs are last of the holy grail in HIV
• No existing drugs target this source of HIV in the

body

• HIV eradication necessary to minimise long-term effects of HIV

infection, including HIV-Associated Neurocognitive Disorders and immune aging

Control +BIT225

* *

BIT225 – Proven Clinical Activity Against HIV

• Phase 1b/2a randomised, placebo controlled, double-blind trial

– 24 patients, HIV-1 positive, treatment-naïve – 10 days dosing with BIT225 (monotherapy)

• Results demonstrated that:

1. BIT225 significantly reduces HIV levels in the macrophage (reservoir) cells in HIV-infected subjects

• 2. BIT225 can cross the blood-brain barrier, opening up the

possibility of treatment of AIDS-related dementia

2 4 6 8 10 12 14 16 5 10 15 20 25 HIV-1 Replication (pg/200uL) Time in Co-culture (days) BIT225 Placebo

Results support a potential role for BIT225 in cure/eradication strategies

BIT225 –Multiple Market Opportunities

• Hepatitis C
• Potential for future combination cocktails with polymerase and protease inhibitors
• Unique mode of action
• Good drug-drug interaction profile
• Limited alternative classes for combinations (prevention of resistance)
• Potential to fill gaps left by other DAA classes
• Add-on to IFN/RBV treatment ex-USA
• HIV/HCV
• Part of combination cocktail with either IFN/RBV and/or other new DAAs
• HIV
• Add-on to anti-retroviral treatment to clean out underlying reservoirs
• Part of future eradication or cure strategies

Dengue Virus Program

• 2.5 billion people (40% world population) live in areas at risk of Dengue
• A leading cause of illness and death in tropics and subtropics
• ~100 million people infected yearly
• No approved vaccine or therapy
• Transmission is by mosquito; most prevention programs target the vector
• Biotron has a number of compounds with promising activity at early stage of

development

• Targeting Dengue M protein –

Similar class to HIV/Vpu and HCV/p7

Biotron Outlook 2013/14

Michelle Miller, CEO; +61 412 313329; mmiller@biotron.com.au 4Q13 1Q14 2Q14

HIV/HCV 6-month, interim data from the Phase 2 HIV/HCV co- infection trial (BIT225-006) HCV Preliminary, interim data from Ph 2, 3 month HCV trial (BIT225- 008) IND Submit an Investigational New Drug ('IND') application for BIT225 to the USA FDA 4Q13 - Commence Ph2 HCV (3 month dosing with IFN/RBV) (BIT225-008)

3Q14 4Q14

Mid ‘14- Complete enrolment of BIT225-008 HIV/HCV 48 week data from the Phase 2 HIV/HCV co- infection trial (BIT225-006)

BIOTRON LIMITED price history chart Key Financials and Facts

KEY FINANCIALS ASX Code BIT Recent Share Price (10 Jan ‘14) A$0.085 52 Week High A$0.15 52 Week Low A$0.08 Shares on Issue 228 million Market Capitalization A$20 m Net Cash (30 Sept ‘13) A$3.5 m BOARD AND MANAGEMENT Mr Michael Hoy Chairman Dr Michelle Miller Managing Director & CEO Dr Denis Wade Non-Executive Director Dr Susan Pond Non-Executive Director Mr Robert Thomas Non-Executive Director Mr Peter Nightingale CFO & Company Secretary

Dr Michelle Miller Managing Director +61 412 313329 mmiller@biotron.com.au www.biotron.com.au