BIOTRON LIMITED — AGM Information 2013

Nov 7, 2013

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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

8 November 2013

The Manager Companies ASX Limited 20 Bridge Street SYDNEY NSW 2000

(26 pages by email)

Dear Madam,

PRESENTATION TO ANNUAL GENERAL MEETING

I attach a PowerPoint presentation which is to be delivered to the shareholders present at today’s Annual General Meeting which is convened to be held at 11.30 am.

Yours faithfully

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Peter J. Nightingale Company Secretary

pjn7478

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ASX:BIT

AGM 8 November 2013

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Milestones

2012/13: Planned
vs
Achieved

ACTIVITY		STATUS	OUTCOME
Complete Ph 2a HIV trial (1Q2013)			PosiAve data reported
Complete Ph 2 HIV/HCV co-infected tri~~al~~ ~~(1H2013)~~		~~~~	~~PosiAve~~ ~~data~~ ~~reported~~
C~~onduct~~ ~~bioequivalence~~ ~~study~~ ~~in~~ healthy volunteers with new BIT225 capsule formulaAon (1H2013)		~~~~	PosiAve data reported
Complete the three-month toxicology st~~udies~~ ~~(1H2013)~~			Supports three-month trial
Commence three-month Phase 2b HCV trial (2H2013)		~~~~	~~Trial~~ ~~iniAaAon~~ ~~site~~ ~~visit~~ ~~scheduled~~
Progress BIT314 through process development, scale-up acAviAes, and preclinical toxicology studies			On hold to conserve funds and focus on BIT225
Report follow-up data from Ph 2a HCV trial			PosiAve 48-week follow-up data reported

~~GLOBAL PERSPECTIVES~~

Progress
in
development
of
new
HCV
drugs
has
been
rapid over
last
12
months -­‐ Update
of
field -­‐ What
does
that
mean
for
Biotron’s
HCV
program? -­‐ Update
on
BIT225
Programs -­‐ Outlook

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• 180
  m
  people
  infected
  worldwide
  (3%
  world
  populaAon);
  130
  m
  are
  chronically ~~infected~~

• HCV
  is
  4x
  more
  prevalent
  than
  HIV

• 4
  m
  paAents
  in
  US
  (2.7
  m
  chronically
  infected)

• 75%
  are
  undiagnosed

• Baby
  boomers
  -­‐

  800,000
  cases
  undiagnosed
  (CDC)

  • 5x
    more
    likely
    than
    other
    adults
    to
    have
    HCV

• Majority
  of
  infected
  paAents
  remain
  untreated
  or
  untreatable

• Standard
  of
  care,
  unAl
  very
  recently,
  has
  been
  interferon
  and
  ribavirin

  • Associated
    with
    side
    effects
    and
    ineffecAve
    in
    ~50%
    of
    paAents

• Significant
  side
  effect
  profile
  –
  high
  drop
  out
  rate

• Documented
  need
  for
  new,
  safer,
  direct-­‐acAng
  anAviral
  (DAA)
  drugs

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Current

Treatment
OpAons

• Standard
  of
  care
  treatment
  has
  been
  interferon
  and
  ribavirin
  (IFN/RBV)

• ~~48 weeks of treatment~~

• Associated
  with
  debilitaAng
  side
  effects
  in
  many
  paAents

  • High
    drop
    out
    rate

• IneffecAve
  in
  ~50%
  of
  cases

  • Genotype
    1
    parAcularly
    resistant
    to
    IFN/RBV

• Industry
focus
has
been
on
developing
new
drugs
that
directly
target
the
virus
i.e. D A A irect-­‐ cAng nAvirals
(DAAs)

• Wish
  list:

• All
  oral
  drug
  regimens

• Less
  toxic
  drugs

• Pan-­‐genotype
  drugs
  that
  target
  all
  HCV
  genotypes
  1
  –
  6

• Shorter
  treatment
  periods

• EffecAve
  treatment
  opAons
  for
  hard-­‐to-­‐treat
  populaAons e.g.
  HIV/HCV
  coinfected
  populaAon

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Selected

Classes
of
HCV
DAA’s

Entry
Inhibitors

Protease
Inhibitors
(NS3) Polymerase
Inhibitors
(NS5B)

Assembly/budding
Inhibitors e.g.
BIT225

Drugs
must
be
used
in combina1on
to
minimise virus
becoming
resistant to
drugs

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Current

HCV
DAA
Approval
Landscape

Protease Inhibitors -­‐ First
generaAon
approved
in
2011/12 -­‐ Boceprevir
and
Telaprevir -­‐ Second
generaAon
expected
to
be
approved
late
2013 -­‐ Simeprevir
(SIM;
Janssen) -­‐ Expected
to
replace
Boceprevir
and
Telaprevir

Polymerase
Inhibitors -­‐ First
approval
expected
in
late
2013 -­‐ Sofosbuvir
(SOF;
Gilead)

2014
and
beyond -­‐ Expect
addiAonal
filings
for
approvals -­‐ New
DAAs
and
new
combinaAons
of
DAAs

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Gen

1
and
2
Selected
Overview

Genotype
1 -­‐ Most
common
variant
in
USA,
Europe
and
Australia -­‐ New
DAAs
(with
and
without
IFN+/-­‐
RBV);
12
weeks
therapy -­‐ Overall
cure
rates
(SVR12) -­‐ Non-­‐cirrhosis
~92% -­‐ Cirrhosis
~80%

Genotypes
2,
4,
5,
6 -­‐ Respond
well
to
12
weeks
of
SOF
+
RBV
(and
others) -­‐ Low
relapse
rate

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Genotype

3

• ~~Genotype 3~~ -­‐ Higher
  prevalence
  in
  lower
  socio-­‐economic
  groups -­‐ Predominant
  variant
  in
  Asia -­‐ Large
  proporAon
  of
  future
  cases
  expected
  to
  be
  gen
  3
  (intravenous
  drug
  users)

• -­‐ Treatment
  with
  new
  DAA
  classes
  is
  more
  problemaAc
  than
  Gen
  1
  and
  2

-­‐ SOF
+
RBV
requires
at
least
24
weeks
dosing OR

• -­‐ Need
  to
  add
  IFN
  back
  in
  i.e.
  SOF
• RBV
• IFN

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80%

62%
30%
12

16

24
weeks
SVR12
Rate
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Why
AddiAonal
Classes
of
DAAs
Are
SAll
Needed (For
All
Genotypes)

• SOF, SIM etc have only been assessed under trial conditions

• Treatment decisions are being made on limited trial data (often Ph 2)

• Real world will impact on SVR rates post-approval

• Patient compliance with taking drugs for extended periods

• Additional drugs may reduce treatment times (ideally to 4 weeks) and COST

• Potential for resistance unless multiple classes of drugs (as per HIV)

• Specific groups not well served with latest drugs, e.g.

• Cirrhotics

• Gen 3

**No

longer
one
single
standard
of
care
–
mulZple
treatment
strategies
on basis
of
genotype,
disease
stage,
etc**

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HIV/HCV

Co-­‐Infected
PopulaAon

• One third of HIV-positives are 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

• • Recent data from SOF + RBV:

• Genotype 1 76% SVR

• • Genotype 2 68% SVR

• • Genotype 3 67% SVR

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BIT225

and
HCV

~~ü Novel, oral, small molecule compound~~ ü Only
one
of
its
class
(p7
inhibitor)
in
clinical
trials ü Inhibits
viral
assembly;
acAve
at
later
stage
of
virus
life
cycle
to
polymerase
and protease
inhibitors

ü Clinically
acAve
against
HCV
genotype
1
(1a
and
1b)
and
genotype
3 ü Doesn’t
readily
generate
resistance

ü Also
acAve
against
HIV

“HepaZZs
C
market
is
forecast
to
grow
by
230%
peaking
at
$15.5bn
in
2022” Source:
Datamonitor
Healthcare

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BIT225

–
Proven
Clinical
AcAvity
Against
HCV

~~BIT225~~		Interferon + Ribavirin	Interferon + Ribavirin	Interferon + Ribavirin	BIT225-005	BIT225-005	BIT225-005	BIT225-005
Placebo
0	4 wks 12 wks				48 wks
Treatment		12 WEEKS Early Virological Response*			48 WEEKS Sustained Virological Response*
400 mg BIT225 + IFN/RBV 200 mg BIT225 + IFN/RBV		86% 88%			100% 88%
Placebo + IFN/RBV		63%			75%
			*virus levels		below limit of detec9on i.e. 50		IU/ml

Clear
demonstraZon
that
BIT225
has
good
anZviral
acZvity
in
hard-­‐to-­‐treat, treatment-­‐naïve
HCV
genotype
1
paZents

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BIT225

–
HIV
/
HCV
Co-­‐Infected
Trial

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BIT225-­‐006

Interferon
+
Ribavirin
ART

BIT225
0

1
wks

5
wks

48
wks
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• Phase
  2
  HIV/HCV
  trial
  -­‐
  completed
  clinical
  phase
  in
  July
  2013

• Genotypes
  1
  and
  3;
  28
  days
  dosing
  in
  combinaAon
  with
  IFN/RBV

• Treatment-­‐naïve
  to
  HCV
  treatment
  with
  RBV
  and/or
  IFN;
  HIV
  controlled
  by anAretroviral
  drugs
  (ART)

• Interim
  12-­‐week
  data
  presented
  at
  AASLD
  conference
  in
  Washington
  DC
  this
  week

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BIT225

–
HIV
/
HCV
Co-­‐Infected
Trial
(cont)

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HCV
RNA
Change
from
baseline
-­‐
G3
1
0
PR
BIT225
603
-­‐
GT3a
602
-­‐
GT3a
606
-­‐
GT3a
-­‐1
607
-­‐
GT3a
-­‐2
609
-­‐
GT3a
610
-­‐
GT3a
-­‐3
611
-­‐
GT3a
612
-­‐
GT3-­‐
-­‐4
-­‐5
LLQ
-­‐6
0
7
14
21
28
35
42
49
56
63
70
77
84
Time
of
Sample
(Day)
HCV
RNA
(Baseline
adjusted
log10
change)
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• At
  12
  weeks
  -­‐
  All
  HCV
  genotype
  3
  paAents
  who
  completed
  treatment
  were clear
  of
  virus

• Rate
  of
  decline
  in
  virus
  levels
  increased
  aner
  addiAon
  of
  BIT225
  at
  day
  7

• • BIT225
  enhanced
  effect
  of
  IFN/RBV
  in
  HIV/HCV
  co-­‐infected
  paAents

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BIT225

–
HIV
/
HCV
Co-­‐Infected
Trial
(cont)

• Genotype
1
response
was
impacted
by
a
geneAc
change
in
IL28B
in
two paAents
–
this
means
that
they
are
unable
to
respond
to
IFN/RBV • Data
from
previous
005
trial
demonstrated
that
BIT225
works
in
gen
1’s

• This
trial
demonstrates
that:

• BIT225
  is
  acZve
  in
  gen
  3

• BIT225
  improves
  outcome
  for
  hard-­‐to-­‐treat
  HIV/HCV
  co-­‐infected paZents

• Data
provides
guidance
for
posiAoning
BIT225
and
design
of
future
trials

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Why

Are
We
Using
IFN/RBV
in
BIT225
Trials?

• ~~Drugs to treat chronic viral diseases such as HIV and HCV can’t be~~

• used on their own

• IFN/RBV has been the only approved treatment for HCV

• Other new DAAs have also been trialled in combination with IFN/RBV

• IFN/RBV + DAA combination data is used to determine what

• genotypes/patient populations, etc that the DAAs work against

• IT DOESN’T MEAN THAT BIT225 IS BEING POSITIONED TO BE

• USED WITH IFN/RBV

• BIT225 can be trialled in combination with other DAAs once they are

• approved

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Where

Do
These
Results
PosiAon
BIT225
in
the New
DAA
World?

~~BIT225 works against HCV genotypes 1 and 3 Well posiAoned for genotype 3, which~~ has
greatest
unmet
need

-­‐ All
paAents
finishing
treatment
responded
with
just
28
days
of
BIT225 -­‐ PotenAal
to
add
to
new
DAAs
e.g.
SOF
+
RBV
to
improve
outcomes
with
shorter treatment
duraAon
in
this
genotype -­‐ HIV/HCV
co-­‐infecteds
have
parAcular
unmet
need

-­‐ PotenAal
to
be
a
second
DAA
class
to
add
to
polymerase
inhibitors
as
protease inhibitors
are
problemaAc
for
this
group -­‐ Do
not
expect
drug-­‐drug
interacAon
issues
with
BIT225
on
basis
of
in
vitro studies
and
outcome
of
the
HIV/HCV
co-­‐infected
trial BIT225
has
added
advantage
due
to
its
unique
anZ-­‐HIV
acZvity

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HIV

–
Towards
a
Cure

• 34
  million
  people
  worldwide
  living
  with
  HIV

• AnA-­‐HIV
  drugs
  (ART)
  have
  improved
  the
  quality
  of
  life
  for
  HIV+ paAents

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• BUT
  –
  ART
  does
  not
  eradicate
  HIV
  infecAon

• Sustained,
  low-­‐level
  HIV
  replicaAon
  occurs
  in
  ART-­‐treated
  paAents

• Reservoirs
  of
  infecAon
  hide
  virus
  from
  the
  immune
  system
  and
  ART

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+BIT225
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• Industry
  is
  now
  focused
  on
  developing
  drugs
  to
  eradicate
  or
  cure
  HIV infecAon

• BIT225
  is
  acZve
  against
  HIV
  in
  the
  monocyte-­‐derived
  macrophage reservoirs

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Reservoirs
are
last
of
the
holy
grail
in
HIV
treatment

Control

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BIT225

–
Proven
Clinical
AcAvity
Against
HIV

• Phase
  1b/2a
  randomised,
  placebo
  controlled,
  double-­‐blind
  trial
  (BIT225-­‐004)

• 24
  paAents,
  HIV-­‐1
  posiAve,
  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
demenZa

Results
support
a
potenZal
role
for
BIT225
in
cure/eradicaZon
strategies

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BIT225

–
Stepwise
Progression
to
CommercialisaAon

• Strategy is guided by:

• Advisory panels of US-based KOLs who are leaders of the field

• Interaction and feedback from US healthcare analysts who specialise in antiviral space

• Interaction and feedback from potential partners

• Biotron continues to engage with industry at different levels

• One-on-one meetings

• Presentations at US corporate healthcare events

• Presentation of key data at major medical/scientific conferences, including prestigious late-breaking sessions

• Potential partners have been caught up in rush to market with other classes of DAAs

• Now know the DAA treatment gaps

• Now know at least 12 weeks dosing is required with current DAAs

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BIT225

-­‐
HCV
Phase
2
Three-­‐Month
Dosing
Trial

~~BIT225~~ Interferon
+
Ribavirin BIT225-­‐008 Placebo 0 4
wks 12
wks 24
wks 48
wks (end
for
Gen
3) (end
for
Gen
1)

• -­‐ Randomised,
  placebo-­‐controlled,
  double-­‐blind
  trial -­‐ 3
  months
  dosing
  with
  BIT225
  in
  combinaAon
  with
  IFN/RBV -­‐ Treatment
  naïve,
  HCV
  gen
  1
  and
  3

• -­‐ Using
  new
  capsule
  formulaAon

• -­‐ Scheduled
  to
  commence
  shortly AIMS:

• -­‐ Demonstrate
  safety
  of
  BIT225
  with
  3
  months
  dosing

• -­‐ Set
  BIT225
  up
  for
  partnering
  with
  other
  DAA
  classes

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Biotron

Outlook
2013/14

4Q13 1Q14 2Q14 3Q14 4Q14 4Q13
-­‐
Commence Mid
‘14-­‐ Ph2
HCV
(3
month Complete HCV Preliminary,
interim dosing
with
IFN/RBV) enrolment data
from
Ph
2,
3 (BIT225-­‐008) of month
HCV
trial BIT225-­‐008 (BIT225-­‐008) HIV IND AddiZonal
data Submit
an from
the
Phase
2a InvesZgaZonal HIV
trial New
Drug ('IND') applicaZon
for BIT225
to
the USA
FDA HIV/HCV Preliminary, interim
data
from the
Phase
2
HIV/ HCV
co-­‐infecZon trial
(BIT225-­‐006)

Michelle Miller, CEO; +61 412 313329; mmiller@biotron.com.au

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BIT225

–MulAple
Market
OpportuniAes

• HepaZZs
C

• PotenAal
  for
  future
  combinaAon
  cocktails
  with
  polymerase
  and
  protease
  inhibitors • Unique
  mode
  of
  acAon

• Good
  drug-­‐drug
  interacAon
  profile

• • Limited
  alternaAve
  classes
  for
  combinaAons
  (prevenAon
  of
  resistance)

• • PotenAal
  to
  fill
  gaps
  len
  by
  other
  DAA
  classes

• • Add-­‐on
  to
  IFN/RBV
  treatment
  ex-­‐USA

• HIV/HCV

• Part
of
combinaAon
cocktail
with
either
IFN/RBV
and/or
other
new
DAAs

• HIV

• Add-­‐on
  to
  anA-­‐retroviral
  treatment
  to
  clean
  out
  underlying
  reservoirs

• Part
of
future
eradicaAon
or
cure
strategies

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ASX:BIT

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Dr Michelle Miller Managing Director +61 2 9805 0488 +61 412 313329 mmiller@biotron.com.au www.biotron.com.au

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