BIOTRON LIMITED - Investor Presentation 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: [email protected] Website: www.biotron.com.au

5 December 2013

The Manager Companies ASX Limited 20 Bridge Street Sydney NSW 2000

(3 pages by email)

Dear Madam

PRESENTATION OF HIV DATA AT INTERNATIONAL HIV PERSISTENCE MEETING

New data from Phase 2a HIV trial presented at HIV Persistence Meeting
BIT225 shown to reduce the pool of virus hidden in reservoirs
Expands on previously announced positive results

Biotron Limited (ASX: BIT) has presented data from its HIV program at the Sixth International Workshop on HIV Persistence during Therapy, being held this week in Miami, FL, USA. The meeting brings together scientists from bench to bedside working on the topics of HIV Persistence, HIV Reservoirs & Eradication Strategies.

Biotron’s Senior Virologist, Dr John Wilkinson, has presented new and updated anti-viral efficacy results from the Company’s phase 2a trial of lead drug candidate BIT225 on 21 HIV infected patients. As previously reported, BIT225 was shown to target and reduce virus levels in monocyte lineage reservoir cells.

The new data shows that BIT225 not only stops the production of new virus in these reservoir cells, but also reduces the quantity of virus in these cells.

Biotron Managing Director Dr Miller commented: "The latest results show that BIT225 is able to clear out underlying virus pools from these reservoir cells. The data support and extend the previously reported encouraging results achieved with BIT225 in HIV infected patients. This drug is a novel compound which is the first in a new class of antiviral drugs that may provide a new approach to the treatment of HIV."

In late 2012, Biotron completed the clinical phase of a Phase 1b/2a trial of BIT225 in HIV-1 infected individuals. The trial, which was performed at Siriraj Hospital, Bangkok, Thailand, was designed to demonstrate that BIT225 is able to target and reduce virus in monocyte lineage cells. During HIV infection, these cells become infected with the virus and are the seeds of hidden HIV pools in patients, setting up long-lived reservoir cell populations in various sites in the body.

The results are important as they suggest that BIT225 has the potential to be included in future HIV elimination or cure strategies. It may provide a way to halt the ongoing cycle of infection and reinfection with virus from these long-lived cells. Targeting virus reservoirs is regarded as the 'holy grail' of current HIV research.

BIT225 is also in development for the treatment of Hepatitis C virus ('HCV'). There are encouraging data in this indication, in HCV mono-infected and HIV/HCV co-infected patients. A phase 2, 3- month dosing trial of BIT225 in HCV genotype 1 and 3 patients is currently in progress.

A copy of the presentation is attached.

Enquiries

Dr Michelle Miller Managing Director Biotron Limited +61-2 9805 0488 +61-(0)412313329

Rudi Michelson Monsoon Communications +61-3 9620 3333

About Biotron and BIT225

Biotron Limited is engaged in the research, development, and commercialisation of drugs targeting significant viral diseases with unmet medical need, with a major focus on HIV and HCV. The Company has BIT225 in clinical development for both HIV and HCV, and also has several earlier stage preclinical and research programs for several other viral infections including Dengue.

Yours sincerely

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Peter J. Nightingale Company Secretary pjn7541

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A
Phase
2a
Study
of
the
Safety,
Pharmacokine7cs
and
An7viral
Ac7vity
of
BIT225
in
Pa7ents
with
HIV-‐1
Infec7on
John
Wilkinson* [1] ,
Craig
Witherington [1] ,
Carolyn
Luscombe [1] ,
Gary
Ewart [1] ,
Kris6n
McBride [1] ,
Nabaya
Tanliang [2] ,
Winai
Ratanasuwan [2] ,
Robert
Murphy [3]
and
Michelle
Miller [1]
1 2 3
Biotron
Limited,
Sydney,
Australia,
Siriraj
Hospital,
Bangkok,
Thailand
and
Northwestern
University,
Chicago,
IL,
US
Introduc6on
Results
–
An6viral
Efficacy
Results
Viral
reservoirs
are
a
significant
obstacle
to
eradica;on
of
HIV-‐1
Table
1.
Baseline
characteris6cs
of
the
study
Figure
4.

BIT225
therapy
results
in
a
significant
infec;on.
Macrophages
are
an
early
target
for
HIV-‐1
infec;on
par6cipants.

The
treated
and
placebo
groups
were
well
reduc6on
in
HIV-‐1
within
the
CD14 [+]
monocytes
of
and
serve
as
long
term
reservoirs
of
the
virus.
Therapeu;c
matched
at
baseline,
with
no
significant
differences
between
the
pa6ents
with
high
viral
loads.
strategies
aimed
at
fully
eradica;ng
HIV-‐1
from
the
host
must
two
groups
in
any
of
the
parameters
measured.
When
the
12
treated
pa;ents
were
split
in
to
2
groups,
also
target
these
infected
cells
to
be
fully
effec;ve.
Total determined
by
the
median
viral
load,
those
pa;ents
with
high

Placebo

BIT225
The
discovery
that
specific
viral
proteins
have
ion
channel
viral
loads
(>4.43)
demonstrated
significantly
less
virus
within

n

21
7
14
ac;vity
(viroporins)
led
Biotron
to
design
a
library
of

250

Female
10
3
7
the
co-‐cultures
of
cells
collected
during
BIT225
therapy.
compounds
with

70%
ac;ve
against
the
Vpu
target.

BIT225

Male
11
4
7

Withdrew
2
0
2*
was
selected
as
the
lead
compound
from
this
library.
It
High
Viral
Load
(n=6) Low
Viral
Load
(n=6)

Mean
Age
29.2
27
30.4
16 16
demonstrates
encouraging
an;-‐HIV-‐1
ac;vity
in
primary
HIV-‐1 VL (copies/mL) 14 14
Day
0
Bleed
human
CD14 [+]
monocyte-‐derived
macrophages
(MDMs).

Median

27,199

20,521

27,997
12 12 Day
5
Bleed
Day
10
Bleed
BIT225
significantly
reduces
virus
release
from
MDMs
with
an

Range

3,560
–
276,930

6,109
–
81,829

3,560
–
276,930
EC
Log

4.43

4.29

4.45
10 10 Day
20
Bleed
50
of
1.1
±
0.4
µM
and
a
TC50
of
212
µM.
8 8

Range

3.55
–
5.44

3.79
–
4.91

3.55
–
5.44
6 6
Here
we
report
on
the
an;viral
effects
of
BIT225
in
the
sejng
CD4 Count (cells/mm3)
4 4
of
a
recent
Phase
1b/2a
clinical
trial
conducted
at
the
Siriraj

Median

475
482
441

Range

261
–
835

261
–
617

299
–
835
2 2
Hospital,
Bangkok,
Thailand
in
HIV-‐1 [+]
individuals.
Using
a
novel

Discon,nued
due
to
headache,
nausea
and
vomi,ng
(grade
1
&
2)
co-‐culture
assay
measuring
infec;ous
virus
from
pa;ent
CD14 [+]

25
Time
in
Co-‐culture
(days)
monocytes,
we
have
demonstrated
that
treatment
with
BIT225
Mann-‐Whitney
p=
significantly
reduced
the
level
of
HIV-‐1
within
these
cells.

The
Ten
days
of
BIT225
was
generally
well
tolerated.
The
0
v
5

0.25

0.09

0.1

0.05

0.04

0.2
results
provide
evidence
that
BIT225
can
target
and
reduce
the
pharmacokine;c
data
suggests
that
adequate
BIT225
levels
in
the
0
v
100
v
20

0.25

0.31

0.42

0.44

0.28

0.25

0.28

0.31

0.37

0.35

0.54
viral
burden
in
cells
of
the
myeloid
lineage
in
a
clinical
sejng.
plasma
were
achieved
in
vivo.
' As
expected,
this
short
dura;on
of
BIT225
had
no
effect
upon
pa;ent
HIV-‐1
viral
load
or
CD4 [+]
T
cell
count.
Conclusion
Aim
1.
Figure
1.
BIT225
results
in
a
reduc6on
in
total
HIV-‐1
DNA
By
directly
measuring
total
HIV-‐1
DNA
within
the
The
aim
of
this
study
was
to
examine
the
effect
of
10
days
of
in
the
monocytes
of
HIV-‐1 [+]
individuals
with
10
days
of
pa;ents’
monocyte
cells,
represen;ng
their
myeloid
BIT225
treatment
on
the
level
of
ac;ve
HIV-‐1
infec;on
in
the
treatment.

Total
HIV-‐1
DNA
in
individuals
receiving
popula;on,
we
have
shown
that
BIT225
reduces
the
myeloid
cellular
reservoirs,
which
persist
irrespec;ve
of
placebo
remained
stable
throughout
the
study.

viral
burden
in
these
cells
following
10
days
of
ac;ve
virus
replica;on
in
T
cells.
This
used
a
novel
endpoint-‐
± ± ± ±
Mean
SE
copy
number
was
1493
593,
1414
655,
547
157
and
treatment
Figure
1.
analysis
method
for
e x
vivo
measurement
of
HIV-‐1
output
from
±
1419
1183
copies/500
ng
DNA
at
days
0,
5,
10
&
20
respec;vely.
cells
of
the
CD14 [+]
monocyte
lineage
aXer
isola;on
from
2.
This
response
was
greatest
in
those
pa;ents
with
higher
BIT225-‐treated
individuals.
100000 total
HIV-‐1
DNA
at
baseline
Figure
2 .
In
contrast
to
HIV-‐1
clinical
trials
using
T
cell-‐targe;ng
drugs,
BIT225 Treated (n=6)
Placebo (n=7) 3.
This
observed
reduc;on
of
virus
within
the
CD14 [+]
this
trial
did
not
aim
to
measure
a
direct
decrease
in
HIV-‐1
viral
10000
monocyte
compartment
by
BIT225,
was
also
supported
load,
nor
increase
in
CD4 [+]
T-‐cell
count:
Such
effects
would
be
using
a
co-‐culture
assay.

The
assay
measures
unlikely
for
a
short
monotherapy
trial
of
BIT225,
a
compound
1000
replica;on
competent
virus
origina;ng
from
these
cells.
which
was
designed
to
target
HIV-‐1
replica;on
in
macrophages
and
myeloid
cellular
reservoirs.
A
reduced
infec,ous
viral
burden
within
the
monocyte
100 popula;on
was
observed
following
10
days
of
BIT225
0 5 10 20 Figure
3 .
Time (days)
Study
Design
4.
In
the
co-‐culture
assay,
the
drug
effect
was
more
A
Phase
1b/2a,
placebo-‐controlled,
randomised
study
evident
in
those
individuals
with
higher
viral
loads
Figure
2.

BIT225
results
in
a
mean
reduc6on
of
63%
in
of
the
safety,
pharmacokine7cs
and
an7viral
ac7vity
Figure
4.
HIV-‐1
copy
number
in
the
monocytes
of
the
HIV-‐1
of
BIT225
in
pa7ents
with
HIV-‐1
infec7on.
seroposi6ve
individuals
following
10
days
of
treatment 5.
No
such
changes
in
virus
burden
within
the
CD14 [+]
Primary
objec7ve (p=0.09). monocytes
were
observed
in
the
placebo
cohort.
4000
BIT225 Treated (n=6)
The
safety
and
tolerability
of
400
mg
of
BIT225
BID
compared
6.
As
expected
with
a
short
dura;on
single
drug
regimen
with
placebo
in
pa;ents
with
HIV-‐1
infec;on
that
were
3000
targe;ng
myeloid
lineage
cells,
no
changes
in
viral
load
an;retroviral
therapy
naïve.
2000 or
the
CD4 [+]
T
cell
count
were
observed
during
the
Secondary
objec7ves
treatment
period.
• 1000

The
pharmacokine;cs
of
400
mg
of
BIT225
administered
daily
7.
BIT225
was
well
tolerated
with
adequate
plasma
levels
on
day
1
&
10
and
twice
daily
on
days
2
–
9.
0
• 0 10 achieved.
Analysis
of
CSF
demonstrated
that
the
drug
is

The
an;viral
ac;vity
of
BIT225.
Time (days)
able
to
cross
the
blood
brain
barrier.
Study
design
• 8.
Since
comple;on
of
this
trial,
an
op;mised
capsule

A
randomised,
placebo
controlled,
parallel,
double-‐blind
Figure
3.

BIT225
therapy
results
in
a
reduc6on
in
virus
study
of
BIT225
in
pa;ents
with
HIV-‐1
infec;on
who
are
formula;on
of
BIT225
has
been
developed
and
tested
in
burden
within
the
CD14 [+]
monocytes.
an;retroviral
therapy
naïve.
healthy
volunteers.
The
amount
of
virus
within
the
CD14 [+]
monocytes
in
the
placebo
•

Open
to
males
and
females,
aged
18
to
65
years,
with
HIV-‐1
group
(n=7)
remained
constant
throughout
the
study,
no
infec;on
(viral
load

5,000
copies/mL;
CD4 [+]
count
350
cells/ Treatment
with
BIT225
reduced
the
virus
burden
in
differences
were
observed
in
the
HIV-‐1
replica;on
rate
in
the
co-‐
mm [3]
)
and
that
are
an;retroviral
therapy
naïve.
monocyte
reservoirs,
par7cularly
for
those
individuals
cultures
of
cells
collected
from
the
4
;me
points
in
the
trial.
•

14
pa;ents
received
400
mg
BIT225
and
7
received
placebo.
with
high
viral
loads.

By
targe7ng
these
cells
and
In
the
BIT225
treated
arm
(n=12),
a
reduced
amount
of
virus
was
preven7ng
(re)seeding
of
the
myeloid
reservoirs,
BIT225
Samples,
CD14 [+]
monocyte
isola7on
and
co-‐culture
assay
detected
in
the
co-‐cultured
cells
from
blood
collected
aXer
5
has
a
poten7al
role
in
the
eradica7on
strategy
of
HIV-‐1.
For
all
pa;ents,
blood
was
collected
on
days
0,
5,
and
10
of
days
of
drug
treatment
when
compared
to
the
day
0
bleed.
This
dosing
and
a
follow
up
visit
at
day
20.

Plasma
was
stored
and
lower
level
of
virus
persisted
out
to
the
day
20
bleed,
indica;ve
CD14 [+]

monocytes
isolated
from
the
21
study
par;cipants
by
of
less
HIV-‐1
present
within
the
myeloid
compartment
in
the
magne;c
bead
sor;ng
at
each
of
these
4
;me
points.

drug-‐treated
pa;ents.
Further
informa6on
= =
Placebo (n 7) BIT225 Treated (n 12)
At
each
of
the
4
;me
points,
total
DNA
was
extracted
from
the
16 16 Contact:

[email protected]
( Senior
Virologist )
isolated
CD14 [+]
monocytes
and
total
HIV-‐1
DNA
copies
14 14
[email protected]
( CEO
&
Managing
Director )
quan;tated
using
RT-‐PCR.

Total
HIV-‐1
DNA
copy
number
was
Day
0
Bleed
12 12
Day
5
Bleed
not
detected
in
all
samples
at
all
;me
points
(placebo
n=7;
10 10 Day
10
Bleed Or
visit:

www.biotron.com.au
Day
20
Bleed
BIT225
n=6).
8 8
6 6
In
real
;me,
isolated
CD14 [+]
monocytes
were
combined
with
Acknowledgements
4 4
We
would
especially
like
to
thank
the
trial
par;cipants
for
their
MT4
T
cells
and
co-‐cultured
ex
vivo
for
25
days.

HIV-‐1
2 2 involvement
in
this
study.

In
addi;on,
a
big
thank
you
to
the
staff
at
replica;on
in
the
co-‐culture
was
determined
by
p24
ELISA
of
ACLIRES
and
the
Department
of
Medicine
at
Siriraj
Hospital
for
their
the
co-‐culture
supernatant
aXer
5,
10,
15,
20
and
25
days
of

25
assistance
with
this
trial
and
making
us
feel
very
welcome
throughout
our
co-‐culture.
Time
in
Co-‐culture
(days)
stay
in
Bangkok.
HIV-‐1
Replica;on
(pg/200uL)
( copies/500 ng)
Log Total HIV-1 DNA
(copies/500 ng)
Total HIV-1 DNA
HIV-‐1
Replica;on
(pg/200uL)
----- End of picture text -----

AI assistant

BIOTRON LIMITED Investor Presentation 2013

64528_rns_2013-12-04_7f6c81b9-c25d-4fff-b51f-2b805f7a8699.pdf

PRESENTATION OF HIV DATA AT INTERNATIONAL HIV PERSISTENCE MEETING

Enquiries

About Biotron and BIT225

AI assistant

BIOTRON LIMITED — Investor Presentation 2013

64528_rns_2013-12-04_7f6c81b9-c25d-4fff-b51f-2b805f7a8699.pdf

PRESENTATION OF HIV DATA AT INTERNATIONAL HIV PERSISTENCE MEETING

Enquiries

About Biotron and BIT225

More from BIOTRON LIMITED

BIOTRON LIMITED Investor Presentation 2013