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6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB WWW.ANTISENSE.COM.AU ANTISENSE THERAPEUTICS LIMITED ABN 41 095 060 745 | Page 1 20 October 2014 Shareholder & Investor Presentations As announced on the 9 th October, Professor Peter Trainer, Chief Investigator of the Phase II clinical trial of ATL1103, will today present to shareholders and investors whilst in Melbourne. Following his presentation the CEO Mark Diamond will give an investor update (copy of these presentations follow this announcement). The Melbourne presentation is also being recorded and will be available for viewing by tomorrow at 12.00pm via a link on the ANP website homepage www.antisense.com.au or directly on the following link: http://webcasting.brrmedia.com/broadcast/127892 Antisense Therapeutics Limited (ASX: ANP) is an Australian publicly listed biopharmaceutical drug discovery and development company. Its mission is to create, develop and commercialise second generation antisense pharmaceuticals for large unmet markets. ANP has 4 products in its development pipeline that it has in-licensed from Isis Pharmaceuticals Inc. (NASDAQ:ISIS), world leaders in antisense drug development and commercialisation - ATL1102 (injection) which has successfully completed a Phase II efficacy and safety trial, significantly reducing the number of brain lesions in patients with multiple sclerosis, ATL1103 a second-generation antisense drug designed to block GHr production and thereby lower blood IGF-I levels and is in clinical development as a potential treatment for growth and other GH-IGF-I disorders, ATL1102 (inhaled) which is at the pre-clinical research stage as a potential treatment for asthma and ATL1101 a second-generation antisense drug at the pre-clinical stage being investigated as a potential treatment for cancer. Contact Information: Website: www.antisense.com.au Managing Director: Mark Diamond +61 (3) 9827 8999 For personal use only

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Page 1: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB WWW.ANTISENSE.COM.AU

ANTISENSE THERAPEUTICS LIMITED ABN 41 095 060 745

| P a g e 1

20 October 2014

Shareholder & Investor Presentations

As announced on the 9th October, Professor Peter Trainer, Chief Investigator of the Phase II

clinical trial of ATL1103, will today present to shareholders and investors whilst in Melbourne.

Following his presentation the CEO Mark Diamond will give an investor update (copy of these

presentations follow this announcement). The Melbourne presentation is also being recorded

and will be available for viewing by tomorrow at 12.00pm via a link on the ANP website

homepage www.antisense.com.au or directly on the following link:

http://webcasting.brrmedia.com/broadcast/127892

Antisense Therapeutics Limited (ASX: ANP) is an Australian publicly listed biopharmaceutical drug discovery and

development company. Its mission is to create, develop and commercialise second generation antisense

pharmaceuticals for large unmet markets. ANP has 4 products in its development pipeline that it has in-licensed from

Isis Pharmaceuticals Inc. (NASDAQ:ISIS), world leaders in antisense drug development and commercialisation -

ATL1102 (injection) which has successfully completed a Phase II efficacy and safety trial, significantly reducing the

number of brain lesions in patients with multiple sclerosis, ATL1103 a second-generation antisense drug designed to

block GHr production and thereby lower blood IGF-I levels and is in clinical development as a potential treatment for

growth and other GH-IGF-I disorders, ATL1102 (inhaled) which is at the pre-clinical research stage as a potential

treatment for asthma and ATL1101 a second-generation antisense drug at the pre-clinical stage being investigated as

a potential treatment for cancer.

Contact Information: Website: www.antisense.com.au

Managing Director: Mark Diamond +61 (3) 9827 8999

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Page 2: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Modern Management of Acromegaly

Peter J Trainer

Christie Hospital

Melbourne

20th October 2014

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Page 3: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Disclosures

Investigator:

Chiasma (Roche), Antisense Pharmaceuticals,

Ipsen, Cortendo

& Novartis (UK CI for LCI699)

Advisory Group Member (unpaid):

Chiasma, Roche, Novartis, HRA Pharma

Antisense Pharmaceuticals

Chairman

Bioscientifica

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Page 4: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Diagnosis can

take many years

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Page 5: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Metabolic Actions of GH

Proteins Increases protein synthesis, increases muscle mass

Lipids Stimulates lipolysis

Inhibits lipogenesis

Decreases adipose mass

Carbohydrates Increases hepatic gluconeogenesis

Inhibits glucose uptake in muscle

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Page 6: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Dose dependent decrease in fat, and increase

in muscle and bone!!!

What every athlete knows!!! F

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Page 7: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Pathogenesis of acromegaly

GH

IGF-I

IGF-I

IGF-I

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Page 8: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Rajasoorya CE 1994 41 95

Length of Survival (years)

0.4

0 5 10 15 20 25

0.5

0.6

0.7

0.8

0.9

1.0

General population

All acromegaly

Acromegaly + diabetes

Acromegaly +

cardiac disease

The Impact of Acromegaly on Survival

Life expectancy

10 years For

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Page 9: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Acromegaly and Mortality

Retrospective study (n=79) Overall mortality (mortality ratio 2.68)

57% deaths cardiovascular

GH <5 mU/l post-treatment - mortality risk normal

Bates QJM 1993 86 293

Therefore reduction of GH <5 mU/l a clinical priority

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Page 10: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Cox

model

predicted

survival

Long-term Mortality After Transsphenoidal

Surgery

Years after surgery

Normal IGF-I

Elevated IGF-I 0.8

0.4

0.2

1.0

0.6

Patient in remission

Patient not in remission

5 10 15 20

Swearingen JCEM 1998 83 3419

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Page 11: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

• restoration of basal GH and IGF-I to normal levels

• relief of symptoms

• reversal of visual and soft tissue changes

• prevention of further skeletal deformity

• normalization of pituitary function

Objectives of therapy in acromegaly

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• prospect of cure

• rapid fall in GH

• decompression

• cost effective

Surgery as primary therapy for acromegaly

Microadenoma (<1 cm)

Surgical cure rate ~90%

Macroadenoma (>1 cm)

Surgical cure rate <50%

Two important determinants of success of surgery

• size of tumour

• the surgeon

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Page 13: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Transsphenoidal Surgery F

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Page 14: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

10

20

30

40

50

60

70

cure

rate

(%)

UK cure rate of patients in

different surgical centres

A B D O L K H T R Q P V U

Bates CE 2008 68 136

UK surgical centres

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Page 15: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

# of operations Complication <200 200-500 >500 Anaesthetic complications 3.5 1.9 0.9* Carotid artery injury 1.4 0.6 0.4* CNS injury 1.6 0.6 0.4* Haemorrhage 2.8 4.0 0.8* Loss of vision 2.4 0.8 0.5* Ophthalmoplegia 1.9 0.8 0.4* Meningitis 1.9 0.8 0.5# Nasal septum perforation 7.6 4.6 3.3* Post-operative epistaxis 4.3 1.7 0.4* Post-operative sinusitis 9.6 6.0 3.6* Hypopituitarism 20.6 14.9 7.2* DI 19.0 NA 7.6* Death 1.2 0.6 0.2*

Complications of pituitary surgery

Ciric Neurosurgery 1997 40 225

Transsphenoidal surgery requires

dedicated surgeons

* P<0.001 #P<0.05 F

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Radiotherapy

Conventional

multi-fractional

• 40 years experience

• mass of data

Gamma Knife LINAC

Stereotactic

• single fraction

• less radiation to surrounding tissues

• the future

• limited experience

LINAC

Gamma Knife®

Proton beam

proton beam

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Page 17: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Dopamine Agonists

Goals

Control GH

Control IGF-I

Improve well-being

Control (normal IGF-I)

bromocriptine 10%

cabergoline 37%

more potent

fewer side effects

twice weekly

Advantages

No hypopituitarism

Oral administration

Rapid onset

Disadvantages

Relatively ineffective

Side effects

Concern over cardiac

• valve fibrosis For

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Page 18: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

ala

thr

trp

gly cys lys asn phe phe

lys

phe thr cys ser

Human somatostatin

Amino acids essential

for receptor binding

Somatostatin Analogues

• inhibit multitude of hormones

• T 1/2 3 minutes

• rebound

• binds all 5 receptor sub-types val

D trp

D bnal cys tyr

lys

cys Thr ol

Lanreotide

thr

D trp

D phe cys phe

lys

cys Thr ol

Octreotide

• more specific

• T1/2 100 min

• no rebound

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Page 19: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Pre-Treatment GH and Outcome in

Acromegalics on Somatostatin Analogues

Primary octreotide therapy

study (POTS)

Pre-treatment Remission rate

GH (mU/l)

<25 100%

25 – 50 75%

>50 33%

Remission Rate %

(GH <5 mU/l)

60

48

54

31

19

14

Pre-Treatment

GH (mU/l)

5-10

10-20

20-30

30-60

60-100

>100

British Acromegaly Register

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Page 20: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Baseline 552 mm3 24 weeks 63 mm3

Difference 88%

Bevan JCEM 2002 87 4554

Tumour shrinkage with LAR as primary therapy

Baseline 61733mm3 24 weeks 29537 mm3

Difference 52%

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Colao JCEM 2014 99 791

Pasireotide v octreotide:

head to head study

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• 191 amino acid GH analogue

• 9 amino acid substitutions

• 4 - 5 PEG moieties

• molecular weight 42 - 46000 D

• half-life >70 hours

• subcutaneous administration

serum GH cannot be used as

a disease marker

GH

Pegvisomant

Goal of therapy - to lower IGF-I into

the age-related reference range

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Page 23: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

80 mg

30 mg

placebo

IGF-I as percent of basal in 46 patients

with acromegaly on weekly pegvisomant

0 7 14 21 28 35 42

40

60

80

100

120

Time (days)

Serum IGF-I

(% of basal)

Treatment

-7 -14

P < 0.05

P < 0.001

van der Lely, ENDO 1998 Abs OR4-1

n=3 - normal IGF-I

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Page 24: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

0 2 4 8 12

10

20

30

40

50

60

70

80

90

100 placebo

10 mg *

15 mg * 20 mg *

Time (weeks)

Serum

IGF-I

(% basal)

IGF-I changes in 112 patients with

acromegaly on daily pegvisomant

* P <0.0001

v. placebo

Similar changes seen in:

• free IGF-I

• IGF-BP3

• ALS

Trainer NEJM 2000 342 1171

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Page 25: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

20

40

60

80

100

Percentage achieving a normal

age-related serum IGF-I with pegvisomant

placebo 10 mg 15 mg 20 mg

%

*

* *

* P <0.0001

v. placebo

Trainer NEJM 2000 342 1171

Dose-dependent fall in:

free IGF-I

IGF-BP3

ALS

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Page 26: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

-6

-5

-4

-3

-2

-1

0

1

2

3

Change in well-being after 12 weeks

of daily pegvisomant

placebo 10 mg 15 mg 20 mg

*

* *

* P <0.05

v. placebo

Well-being

( basal)

Benefit in:

perspiration

energy levels

soft tissue swelling

Trainer NEJM 2000;342:1171 Trainer NEJM 2000 342 1171

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Ring size after 12 weeks of

daily pegvisomant

-3

-2

-1

0

1

*

placebo 10 mg 15 mg 20 mg

* P <0.005

v. placebo

Ring

Size

( basal)

*

Trainer NEJM 2000 342 1171

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Page 28: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Serum IGF-I

(ng/mL)

500

1000

1500

2000

2500

Age (years)

55+ 16-24 25-39 40-54

IGF-I at baseline and after 12 months of

pegvisomant

van der Lely Lancet 2001 358 1754

97% normalisation of IGF-I

maximum dose 40 mg/day

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Page 29: Shareholder & Investor Presentations - ASX · 6 WALLACE AVENUE, TOORAK VIC 3142 AUSTRALIA TEL . +61 (3) 9827 8999 FAX +61 (3) 9827 1166 WEB ANTISENSE THERAPEUTICS LIMITED ABN 41 095

Percentage of patients with a

normal IGF-I in the observational

ACROSTUDY register

1 2 3 4 5

%

Years of treatment

10

20

30

40

50

60

70

80

90

100 F

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A Phase II Randomised, Open-Label, Parallel Group Study

of the Safety, Tolerability, Pharmacokinetics and Efficacy

of Two Subcutaneous Dosing Regimens of ATL1103 in

Patients with Acromegaly

PJ Trainer, J Newell-Price, J Ayuk, S Aylwin, A Rees, WM Drake, P Chanson,

T Brue, S Webb, C Fajardo, J Aller, A McCormack, D Torpy, G Tachas,

L Atley, M Bidlingmaier

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ATL1103 antisense 20mer oligonucleotide

directed at GH receptor Wt 7164 D

19 internucleotide linkages of the

oligo are O,O-linked

phosphorothioate diester

Nucleotides 1 to 5 and 15 to 20 are

2’-O-(2-methoxyethyl) modified

ribonucleosides,

Nucleotides 6 to 14 are 2’-

deoxyribonucleosides

All cytosines are 5-methylcytosines

Chemical, non-biological

20mer phosphorothioate backbone

5’ 3’

“2’-MOE” (RNA)

“2’-MOE” (RNA) 2’-deoxy “gap” (DNA)

5 10 5 RNaseH active

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Tissue and Cellular PK of ASOs

Strong PK/PD correlation in

• Kidney

• Liver

• Bone marrow

• Adipose tissue

• Spleen, lymph nodes

• Lung (aerosol)

• Cancer

• Sites of inflammation

• Eye (Intravitreal)

• CNS (ICV or IT)

Bone

Kidney

Liver

Liver half-life >3 weeks

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-25

-20

-15

-10

-5

0

5

10

15

0 7 14 21 28 35

Day

IGF-I

ALS

GHBP

IGF-BP3

IGF-II

ATL1103 Phase I pharmacodynamic study

250 mg - six doses over 3 weeks (on Day 1, 3, 5, 7, 14 & 21)

Intent to treat population: n=8

ATL1103 therapy

%

change %

change

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Phase 2, randomised, open-label, parallel group

study (EudraCT 201200314730)

33

Ethical approval obtained in each jurisdiction

Powered for 24 patients

Inclusion criteria included:

active acromegaly (IGF-I >130% ULN)

washout from medical therapy (Long acting SMS

analogues 4 months, DA 6 - 8 weeks)

Exclusion criteria included:

tumour within 3 mm of optic chiasm

pituitary surgery within 3 months

radiotherapy within 1 year

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Protocol

MRI MRI

ATL1103 subcutaneously for 13

weeks (3 doses in first week)

Randomised to:

200 mg once weekly

or

200 mg twice weekly

IGF-I & GH assay

IDS iSYS

Bidlingmaier

JCEM 2014 99 1712

OGTT OGTT

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End-Points

Safety

Pharmacokinetics

Efficacy

Primary

The percentage change in IGF-I at week 14

Secondary

% of patients with a normal IGF-I at week 14

% of patients with a normal IGF-I at anytime

Changes in GHBP, BP-3, ALS & IGF-II

Changes in AcroQoL, S&S, size of ring finger

Changes in GH, insulin & glucose

Results presented pending

confirmation after database lock

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200 mg 200 mg

once weekly twice weekly

N 13 13

Age 48 ± 14 53 ± 17

Gender (M/F) 5/8 6/7

Weight (kg) 97 ± 20 85 ± 25

Prior RT 6 (46%) 5 (38%)

Prior Surgery 13 (100%) 12 (92.3%)

Patients F

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Results – Safety End Point 200 mg 200 mg

once weekly twice weekly

Withdrawals 1 1

Reason for withdrawal withdrew consent withdrew consent

after last drug dose after last drug dose

Serious AE 3 (1 patient) - 1 – not related to

unlikely drug related drug

Treatment Emergent AE 131 (11 patients) 178 (11 patients)

Patients with ISR 10 (76.9%) 11 (84.6%)

Mild 8 6

Moderate 2 5

Severe 0 0 For

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Regimen 1 (N=13) Regimen 2 (N=13) Total (N=26)

n N (%) n N (%) n N (%) INJECTION SITE ERYTHEMA 11 6 (46.2%) 28 4 (30.8%) 39 10 (38.5%)

INJECTION SITE PRURITUS 3 3 (23.1%) 25 4 (30.8%) 28 7 (26.9%)

INJECTION SITE REACTION (unspecified) 12 2 (15.4%) 11 3 (23.1%) 23 5 (19.2%)

INJECTION SITE PAIN 5 4 (30.8%) 6 3 (23.1%) 11 7 (26.9%)

INJECTION SITE BRUISING 5 2 (15.4%) 4 3 (23.1%) 9 5 (19.2%)

INJECTION SITE SWELLING 0 0 6 3 (23.1%) 6 3 (11.5%)

INJECTION SITE IRRITATION 1 1 (7.7%) 4 2 (15.4%) 5 3 (11.5%)

INJECTION SITE MASS 1 1 (7.7%) 3 2 (15.4%) 4 3 (11.5%)

HEADACHE 21 5 (38.5%) 5 3 (23.1%) 26 8 (30.8%)

ARTHRALGIA 4 3 (23.1%) 4 1 (7.7%) 8 4 (15.4%)

RASH 3 1 (7.7%) 5 2 (15.4%) 8 3 (11.5%)

FATIGUE 3 2 (15.4%) 4 3 (23.1%) 7 5 (19.2%)

CONSTIPATION 3 2 (15.4%) 2 2 (15.4%) 5 4 (15.4%)

DIARRHOEA 3 2 (15.4%) 2 2 (15.4%) 5 4 (15.4%)

HYPERHIDROSIS 1 1 (7.7%) 4 2 (15.4%) 5 3 (11.5%)

LETHARGY 0 0 4 1 (7.7%) 4 1 (3.8%)

PARAESTHESIA 4 1 (7.7%) 0 0 4 1 (3.8%)

URINARY TRACT INFECTION 3 2 (15.4%) 0 0 3 2 (7.7%)

DIZZINESS 0 0 3 2 (15.4%) 3 2 (7.7%)

Treatment-Emergent Adverse Events

with more than two occurrences

N = number of events, N = number of patients; % percentage of patients

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Change in IGF-I with 13 weeks of ATL1103

-100

-80

-60

-40

-20

0

20

0 2 4 6 8 10 12 14 16 18 20

Regimen 1

Regimen 2

200 mg once weekly

200 mg twice weekly

ITT population

Weeks

ATL1103

%

change

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0

100

200

300

400

500

600

700

Regimen 1 Regimen 2

IGF

-I (

ng/m

L)

IGF-I (ITT population): Mean ± SEM

Baseline Mean

Week 14 Mean

26% lower than baseline

(P <0.0001)

IGF-I

(ng/ml)

200 mg

once weekly

200 mg

twice weekly

Change in IGF-I with 13 weeks of ATL1103

Week

0

Week

0

Week

14

Week

14

mean IGF-I 2.6 times ULN Rate of IGF-I normalisation

200 mg 200 mg

once weekly twice weekly

Week 14 1 1

Anytime 1 2 (15.4%)

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Scatterplot of % change in IGF-I vs dose/kg

% delta

IGF

week 14

-60

-50

-40

-30

-20

-10

0

10

20

30

40

50

Dose/kg (mg/kg/week)

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 -60

-50

-40

-30

-20

-10

0

10

20

30

40

50

Slope = -8.27, P = 0.0001

ATL1103 200 mg/wk

ATL1103 400 mg/wk

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Scatterplot of % change in IGF-I vs dose/kg

% delta

IGF

week 14

-60

-50

-40

-30

-20

-10

0

10

20

30

40

50

Dose/kg (mg/kg/week)

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 -60

-50

-40

-30

-20

-10

0

10

20

30

40

50

Slope = -8.27, P = 0.0001

ATL1103 200 mg/wk

ATL1103 400 mg/wk

Females

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GH levels during a 75 gm oral glucose

tolerance test

0

2

4

6

8

10

12

14

0 20 40 60 80 100 120 140 0

2

4

6

8

10

0 20 40 60 80 100 120 140

200 mg

once weekly

200 mg

twice weekly

Screen

Week 14

P=0.97 P=0.001

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0

2

4

6

8

10

12

14

16

18

20

1 2

200 mg

once weekly

200 mg

twice weekly

S&S

NS

NS

Change in Signs & Scores with ATL1103

Week

0

Week

0

Week

14

Week

14

Ring size 200 mg 200 mg

once weekly twice weekly

Mean change -0.62 -0.92

P=0.17 P=0.02

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AcroQol: Global score

ITT population: Mean ± SEM

0

10

20

30

40

50

60

70

80

Regimen 1 Regimen 2

Global score

200 mg

once weekly

Week

0

Week

0

Week

14

Week

14

200 mg

twice weekly

GHBP, IGFBP3,

ALS, IGF-II

not yet available

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Summary: Safety endpoints

No patient withdrawals or SAEs related to ATL1103

Well tolerated

Injections site reactions most reported adverse event

(AE):

all mild to moderate

No flu-like symptoms

Liver enzymes elevations in two patients

Transient platelet reductions in one patient

Positive safety profile suggests ATL1103 may be

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Summary: Efficacy endpoint (IGF-I)

200 mg once weekly for 13 weeks did not result in a

change in mean IGF-I

2 x 200 mg/week ATL1103

26% mean reduction of IGF-I one week after 13 weeks

(P <0.0001)

IGF-I had not reached nadir by week 13

IGF-I “normalised” in two patients

Dose-response relationship with ATL1103

(mg/kg/week) vs change in IGF-I

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Conclusions

The data indicate that a larger dose of ATL1103

administered for longer should be well tolerated and result

in normalisation of IGF-I in a significant number of patients

with acromegaly

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Antisense Therapeutics Ltd ASX:ANP

Investor Update – October 2014

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Forward Looking Statements

This presentation contains forward-looking statements regarding the Company’s

business and the therapeutic and commercial potential of its technologies and

products in development. Any statement describing the Company’s goals,

expectations, intentions or beliefs is a forward-looking statement and should be

considered an at-risk statement. Such statements are subject to certain risks and

uncertainties, particularly those risks or uncertainties inherent in the process of

developing technology and in the process of discovering, developing and

commercializing drugs that can be proven to be safe and effective for use as human

therapeutics, and in the endeavor of building a business around such products and

services. Actual results could differ materially from those discussed in this

presentation. Factors that could cause or contribute to such differences include, but

are not limited to, those discussed in the Antisense Therapeutics Limited Annual

Financial Report for the year ended 30 June 2014 copies of which are available from

the Company or at www.antisense.com.au.

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Antisense Therapeutics Ltd

Long standing strategic collaboration with Isis Pharmaceuticals Inc, world leaders in

antisense drug development (Isis partnered with GSK, Pfizer, Genzyme, Biogen Idec)

Isis collaboration provides ANP with access to ribonucleic acid (RNA) targeted antisense

drugs (ATL1103 for acromegaly, ATL1102 for MS, ATL1101 for cancer)

Renewed global interest in RNA targeted technologies from investors and Big Pharma Co’s

ANP developing drugs for diseases with large unmet medical need and with potential

significant competitive advantages based on the Isis 2nd generation antisense technology

Advanced development pipeline for multiple disease applications including Acromegaly,

Multiple Sclerosis, and Cancer

Only Australian Biotech company with two drugs with positive Phase II clinical data

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Key Achievements 2014

• ATL1103 for Acromegaly

Phase 2 clinical trial – completion of trial and reporting of successful efficacy results

Positioned to move into Phase III stage of development with partner

Phase II data presented at International Scientific Congress by Chief Investigator

Canadian patent granted

• ATL1102 for MS

Request submitted for US FDA Pre-IND assessment for a Phase 2b clinical trial

ATL1102 Phase 2a MS trial results published in the leading Medical Journal Neurology

US and EU patent allowances

• Corporate

Engaged US-based Advisory firm Destum Partners to advance project partnering plans

Strengthened Balance sheet with Capital Raising and receipt of R&D Tax credit

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Pipeline Program

Pipeline drugs are all antisense compounds via the Isis collaboration

PRODUCT INDICATION RESEARCH PRECLINICAL PHASE I PHASE II PHASE III

ATL1103 s.c. injection

Acromegaly

ATL1102 s.c. injection

Multiple Sclerosis

ATL1101 s.c. injection

Prostate Cancer

ATL1102 inhaled

Asthma

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ATL1103 improving on current treatments

Pegvisomant (Somavert®) ATL1103 Target Product Profile (TPP)

In clinical trial effective in greater % of patients

in normalising sIGF-I than somatostatins

Broad based efficacy like Somavert

Average treatment cost of $60K/annum (up to

$90K/annum)

Lower cost of therapy due to less

expensive cost of manufacture

Limited by high cost, inconvenient

administration

• lyophilized powder requiring reconstitution

and daily dosing regimen

More convenient dosing/administration

regimen

• prefilled syringe; once/twice weekly

dosing for improved patient compliance

Comparing second line therapy Somavert® to ATL1103 est. sales of > US$200m/year

• Low Somavert® market penetration (est. ~25% of 1st line treatment failures) likely due to high cost,

inconvenient administration, and daily dosing

• ATL1103 has potential to convert share from Somavert® and for use with currently untreated patients

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ATL1102 for Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic, progressive, and

debilitating autoimmune disease that affects central

nervous system, brain and spinal cord

• Affects 400,000 people in the U.S. and > 2.1 million

worldwide

• Global sales for MS drugs in 2013 were US$14 Billion

• ATL1102 is an antisense inhibitor of VLA-4 protein a

clinically validated target in MS by drug Tysabri®

(monoclonal antibody drug to same target)

• Tysabri® current efficacy benchmark (most potent) for

treatment of RR-MS; 2013 sales of US$1.6 Billion

• Tysabri® can cause a potential lethal viral brain infection

- progressive multi focal leukoencephalopathy (PML)

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ATL1102 for Multiple Sclerosis

ATL1102 Development status

• Successful Phase 2a trial completed in

patients with Relapsing Remitting-MS

• Met primary end point after only two months of

dosing reducing the cumulative number of new

active brain lesions by 54.4% (p=0.01)

compared to placebo

• ATL1102 demonstrated comparable/potentially

superior activity to Tysabri® at same stage

development

• Results recently published in the Journal of the

American Academy of Neurology

(A) Cumulative number of new active lesions and

(B) number of new active lesions

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ATL1102 Opportunity in MS

New US and EU patents granted to 2029 and potentially extendable to 2034

Parameter ATL1102 Tysabri®

Efficacy Highly potent Highly potent

Safety Well tolerated Safety concerns

Route of administration Self-administered IV infusion

Manufacturing Less expensive More expensive

ATL1102 has the potential to be well differentiated from Tysabri®

Next step - potential Phase 2b study of

ATL1102 in MS patients

FDA Pre-IND assessment of ANP’s

Phase 2b clinical trial design: Goal

date was 17 October 2014

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Corporate Structure

Top 20 Shareholders as at 17 October

POLYCHIP PHARMACEUTICALS PTY LTD 10,190,649

ISIS PHARMACEUTICALS INC 5,880,833

MR JASON ERIC CONSTABLE & MRS CATHERINE

CONSTABLE 5,500,000

SYNGENE LIMITED 4,140,934

CITYCASTLE PTY LTD 3,949,999

CITICORP NOMINEES PTY LIMITED 2,766,736

BAYSPEC PTY LTD 2,400,000

SKED PTY LTD <SUPER FUND A/C> 2,289,462

FLINTBERG PTY LTD <OR SUPERANNUATION FUND A/C> 2,027,500

MRS LORRAINE SANDRA MOSES 1,600,000

MR NORMAN CHI WING TANG & MRS TERESA KIT CHING

TANG 1,350,000

SYED CORPORATION PTY LTD 1,162,179

MR MICHAEL ANDREW CLARK 1,114,938

MR LESLIE SMITH 1,100,000

MR MARK DIAMOND 1,053,567

MR JAMES EDWARDS 1,051,500

DR HUY TRAN 1,016,000

ARMDIG PTY LTD 1,000,000

MR LARRY HUI 1,000,000

DABCO HOLDINGS PTY LTD 925,000

Key Financials

Market Capitalisation A$16 million

Cash as at 30 June 2014 * A$1.3 million

Ordinary shares on Issue 152 million

Share price $0.105

Top 5 Shareholders %

CIRCADIAN TECHNOLOGIES 14,331,583 9.4%

LEON SERRY & ASSOCIATED

COMPANIES 6,512,794 4.3%

MR J & MRS C CONSTABLE 5,890,000 3.9%

ISIS PHARMACEUTICALS INC 5,880,833 3.9%

CITICORP NOMINEES PTY LIMITED 2,766,736 1.8%

* Capital Position (post 30 June)

Share Placement - $840K - September

R&D Tax Incentive - $1.14M - October

Board participation in placement - $100K - November

Share Purchase Plan - $1.5M - November

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Share Purchase Plan (SPP)

• The Company intends to raise approximately A$1.5 million via the SPP (first $1 million underwritten)

• The purpose of the SPP is to provide eligible shareholders with the opportunity to invest in ANP

ordinary shares at the same offer price as the recent placement, without brokerage or other

transaction costs

• The capital raised under the placement and the SPP will be utilised to progress partnering plans for

ATL1103 for acromegaly, FDA interactions on a potential Phase IIb study for ATL1102 for MS, and the

planned higher dose clinical trial of ATL1103 in acromegalic patients

Timetable

Event Date

Record date of SPP Wednesday 24 September 2014

Announcement of the SPP Thursday 25 September 2014

Opening date for the SPP and Mail out of SPP

Documentation Tuesday 7 October 2014

Closing Date of the SPP Friday 31 October 2014

Annual General Meeting of Shareholders Thursday 6 November 2014

Allotment and Issue of SPP Shares 10am (AEDST) Wednesday 12 November 2014

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Investment Highlights

RNA based technologies continuing to see investor and Big Pharma interest

Commercialising platform technology with world leader in RNA therapeutics, Isis Pharmaceuticals

Antisense technology validation provided by successful clinical progress (1 drug on market and 32 drugs in development) and licensing deals with Big Pharma

2 advanced development programs with significant commercial potential

• ATL1103 in Acromegaly

• Primary efficacy endpoint met in Phase II clinical trial

• Discussions underway with potential partners for Phase III development

• ATL1102 in MS

• Successful Phase 2a trial in RR-MS patients – results recently published in leading Scientific Journal NEUROLOGY

• FDA’s Pre-IND assessment of ANP’s proposed Phase 2b clinical trial design – FDA written response due any time now! F

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