antisense therapeutics to present at bio ceo & investor ...2012/02/13 · mobilization, asthma,...
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13 February 2012 Antisense Therapeutics to Present at BIO CEO & Investor Conference
Antisense Therapeutics Ltd. (ASX:ANP) today announced that Chief Executive Officer and Managing Director, Mark Diamond, will give a presentation at the the 14th Annual BIO CEO & Investor Conference at The Waldorf Astoria Hotel in New York City on February 13, 2012 at 11.00am (New York, NY, USA time).
The presentation will be followed by a question and answer session and a live webcast may be accessed on the following link: http://www.veracast.com/webcasts/bio/ceoinvestor2012/44107145.cfm The webcast can also be accessed via the Company’s website, www.antisense.com.au. A replay of the presentation will be archived for 90 days after the conference, at the same location.
The BIO CEO & Investor Conference is the largest independent investor conference focused on publicly-traded biotechnology companies. The conference features issue-oriented plenary sessions, educational sessions focused on hot therapeutic areas and key business issues, company presentations, one-on-one meetings and networking opportunities.
About the Company 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. ATL1102 (injection) has successfully completed a Phase II efficacy and safety trial, significantly reducing the number of brain lesions in patients with multiple sclerosis. ATL1103 is 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 vision disorders. ATL1102 (inhaled) is at the pre-clinical research stage as a potential treatment for asthma. ATL1101 is a second-generation antisense drug at the pre-clinical stage being investigated as a potential treatment for prostate cancer. Contact Information: Website: www.antisense.com.au Managing Director: Mark Diamond +61 (3) 9827 8999 Investor Relations: Simon Watkin +61 (0) 413 153272 F
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Antisense Therapeutics Ltd
ASX:ANPASX:ANPOTC:ATHJY
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Forward Looking Statements
This presentation contains forward-looking statements regarding thecompany’s business and the therapeutic and commercial potential of itscompany s business and the therapeutic and commercial potential of itstechnologies and products in development. Any statement describing thecompany’s goals, expectations, intentions or beliefs is a forward-lookingstatement and should be considered an at-risk statement. Suchstatements are subject to certain risks and uncertainties, particularly thoserisks or uncertainties inherent in the process of developing technologyand in the process of discovering, developing and commercialising drugsthat can be proven to be safe and effective for use as humanthat can be proven to be safe and effective for use as humantherapeutics, and in the endeavour of building a business around suchproducts and services. Actual results could differ materially from thosediscussed in this presentation. Factors that could cause or contribute tosuch differences include, but are not limited to, those discussed in theAntisense Therapeutics Limited Annual Report for the year ended 30 June2011, copies of which are available from the company or atwww antisense com auwww.antisense.com.au.F
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Investment Highlights
ANP is developing antisense drugs for a variety of diseases with unmet medical need and significant commercial potentialg p
ANP has a technology collaboration with Isis Pharmaceuticals Inc, world leaders in antisense drug development and commercialisation and major ANP shareholder. ANP has exclusive world-wide rights to 3 compounds in-licensed g pfrom Isis
Attractive and advanced product pipeline – ATL1101, ATL1102 & ATL1103 for multiple disease applications including cancer, multiple sclerosis, stem cell p pp g pmobilization, asthma, growth and diabetes associated disorders
• Recently completed successful human trial on exciting antisense drug ATL1103 for growth, cancer and diabetes associated disordersg
• Partnering arrangement established to advance prostate cancer drug ATL1101 into clinical trials
• New stem cell mobilization opportunity for ATL1102 identified• New stem cell mobilization opportunity for ATL1102 identifiedFor
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Antisense Therapeutics Limited
• Based in Melbourne, Australia• Listed on Australian Stock Exchange (ASX)
in 2001 (ASX:ANP)
Board of Directors• Mark Diamond – MD and CEO 10 years (Ex Faulding
( )• Level 1 ADR listing in US (OTC:ATHJY)
Mark Diamond MD and CEO 10 years (Ex Faulding – Project Planning/International Business Development); 25 years experience in pharma/biotech industry
• Bob Moses – Chairman (Ex Vice President CSL); 35• Bob Moses – Chairman (Ex Vice President CSL); 35 years experience in pharma/biotech industry
• Dr. Chris Belyea – (Ex CEO Metabolic Pharmaceuticals and Licensing & Projects Manager Circadian)
Market Capitalisation – A$20 million (undiluted)Circadian)
• Dr. Graham Mitchell – Foursight Associates (Ex Director of Research CSL)
• Prof George Werther – Director Dept of
Cash as at 31 December - A$1.5 million
Options with expiry July’12 - A$1.4 million (if fully exercised)
Prof. George Werther Director Dept. of Endocrinology & Diabetes Royal Children’s Hospital
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Antisense Technology
• Rationally designed to block the production of disease causing p gproteins by binding to the specific messenger RNA sequence
• Highly targeted and potent g y g ptherapeutics
• 2nd generation antisense technology= modifications to drug chemistry to g yincrease potency and stability
• Lower dose and more cost effective;
• Increased stability allows more convenient dosing regimes; and
Broad disease application• Broad disease applicationFor
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ANP/Isis Pharmaceuticals Partnership
Isis Pharmaceuticals Inc.
• Leaders in RNA therapeuticsLeaders in RNA therapeutics
• Over 1500 patents
• 28 drugs in development
• KYNAMRO (mipomersen) for cholesterol reduction in high risk individuals partnered with Genzyme. EU filing submitted. US NDA filing planned for 1’Q’12
• Partnerships with Major Pharma Co’s e g GSK Genzyme Biogen Idec and• Partnerships with Major Pharma Co s e.g., GSK, Genzyme, Biogen Idec and Lilly
ANP/Isis Partnership
• Worldwide exclusive licenses covering all therapeutic indications
• Isis provide expert guidance on antisense drug development
• Manufacture of cGMP material for human trials• Manufacture of cGMP material for human trialsFor
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ANP Product Research & Development Pipeline
PRODUCT INDICATION RESEARCH PRECLINICAL PHASE I PHASE II PHASE III
ATL1102 multiple sclerosis
s.c. injection
ATL1103 lATL1103 acromegaly, cancer,
s.c. injection retinopathy, nephropathy
ATL1102 stem cell mobilization for s.c. injection stem cell transplantation
ATL1101 prostate cancers.c. injection
All pipeline drugs are 2nd generation antisense compounds derived via Isis collaboration
ATL1102 asthma
inhaled
All pipeline drugs are 2nd generation antisense compounds derived via Isis collaborationFor
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ATL1103 – Antisense Drug to the Growth Hormone receptor
• 2nd generation antisense inhibitor to the Growth Hormone receptor (GHr)
ATL1103 reduces liver GHr &blocks GH action on the liverHormone receptor (GHr)
• Acromegalics have elevated levels of both serum GH and IGF-I (sIGF-I)
blocks GH action on the liver
• Normalising sIGF-I is the treatment goal
• GHr is a clinically validated target in the treatment of acromegaly
• IGF-I has a role in the pathogenesis of diabetic retinopathy, nephropathy and certain cancers
• sIGF-I is associated with clinical improvement GHr
X
p
Reducing IGF I in bloodReducing IGF-I in blood
Adapted from neurosurgery.ucla.edu/body.cfm?id=101
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ATL1103 in Acromegaly
• Acromegaly is caused by a benign tumour of the pituitary gland
• Tumors over-produce GH leading to elevated sIGF-I causing enlargement of organs and bones of the face feet and hands Can lead to diabetes hypertension cancerbones of the face, feet and hands. Can lead to diabetes, hypertension, cancer
• Affects ~85 adults per million in the US and Europe (~85,000 adults)
• Approx 60% of acromegaly patients are treated (sIGF-I normalised) by surgical removal of th t S f il i d th t li th i IGF Ithe tumour. Surgery failures require drug therapy to normalise their sIGF-I
• Somatostatin agonists of somatostatin 2 receptor (e.g. octreotide) are first line drug therapy -effective in up to 60-65% of cases
• Treatment costs up to A$30K/annum
• Sales in acromegaly ~$1Billion
• Pegvisomant (Somavert®) GHr antagonist• In clinical trial effective in greater % of patients in normalizing sIGF-I than somatostatins
• Sales of > $200 million/annum: Treatment costs of A$60K/annum or more
• Use and effectiveness in clinical practice is limited by high cost, inconvenient administration and dosing p y g , gregimen (e.g. daily injection) negatively impacting its sales potentialF
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ATL1103 Market Positioning – potential advantages over existing GHr antagonist therapy Somavert ®
ATL1103• Price (≤ A$30K/annum)
Somavert ®
• >US $60,000/annum
VS
• Potential for once weekly or less often injection
• Solution in vial or pre-filled syringeo Allows for convenient self
• Daily injection
• Lyophilized powder
o Needs reconstitution, complicating o Allows for convenient self administration by patient
• Effects on GH o Mechanism of action and preliminary
, p gadministration, thereby often requiring professional health-carer assistance
• Effects on GHU d i bl i i GH ( th
p ydata suggests drug may not increase GH
• Monitoring of GH not compromised by cross reaction issues in GH assays
o Undesirable increases in GH (more than 2X)
• Difficulties in monitoring GH due to cross reaction of Somavert ® in GH assayscross reaction issues in GH assays
• Effects on tumour sizeo May not increase tumour size - to be
assessed in clinical studies
y• Effects on tumour size
o Concern regarding tumour size increases noted with treatment in some
ti t d th f ipatients and therefore requires monitoring
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ATL1103 Phase 1 clinical trial
Randomised, placebo-controlled, double-blind single ascending dose and multiple dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ATL1103 in healthy male subjects
Stage A: Single Ascending Dose (SAD)
• 4 cohorts (25, 75, 250, and 400mg)
• 6 subjects (4 active, 2 placebo)
• Full safety monitoring
Stage B: Multiple dosingg p g
• Single dose cohort (250mg)
• 12 subjects (8 active, 4 placebo)
• Six doses over 3 weeks (on Day 1, 3, 5, 7, 14 & 21). Last visit Day 35 monitoring
• Full safety monitoring
• Serum IGF-I, GH, IGF-BP3, ALS and GHBP levels monitored, , ,For
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ATL1103 Phase I trial: Key safety findings
• ATL1103 was safe and generally well tolerated at the doses tested. No deaths or other serious adverse events (AE) reported
• Stage A: 24 treatment‐emergent AEs (TEAE) (19 in the 16 ATL1103‐treated subjects, 5 in the 8 placebo‐treated subjects), all reported as mild or moderate. In ATL1103-treated subjects, most common AE’s reported were pain at i j ti it h d h i fl lik illinjection site, headache, influenza‐like illness
• Stage B: 25 TEAE (18 in the 8 ATL1103‐treated subjects; 7 in the 4 placebo‐treated subjects), all reported as mild. In ATL1103 ‐treated subjects th t l t d AE i j ti it tithe most commonly reported AE were injection site reactions
• In Stage B increased ALT levels were reported for one subject at Day 11. ALT levels returned to the normal range by pre‐dose day 21 and remained within
l f th t f th t dnormal range for the rest of the study
• No clear differences in safety as assessed by clinical laboratory tests, vital signs, and ECG assessments between ATL1103 and placebo treatments and no apparent dose related trendsno apparent dose-related trendsF
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ATL1103 Phase I trial: serum IGF-I suppression
In Stage B there was a clear trend for mean serum IGF-I levels to be lower than baseline on Days14, 21, 28 and 35 with a statistically significant effect on Day 21
Pre‐dose IGF‐I: 36.57 ± 13.16 nmol/L:mean ± SD Study day Change from pre‐dose Probability < (‐t)ay y g p
Mean ± SD (% change from pre‐dose) y ( )
Day 3 + 2.65 ± 9.47 (12%) > 0.500Day 5 + 0.32 ± 7.42 (6%) > 0.500Day 7 + 0.77 ± 7.51 (6%) > 0.500Day 14 ‐1.43 ± 7.19 (‐2%) 0.323 Day 21 ‐3.40 ± 3.59 (‐7%) 0.034 Day 28 ‐3.43 ± 7.53 (‐7%) 0.157Day 35 ‐1.9 ± 5.08 (1%) 0.201y ( )
a 1-sided t-test on change from pre-dose at each time point; alternate hypothesis is suppressionPer protocol population; (n=6 at each time point)For
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ATL1103 Phase I trial: suppression of target and markers of GH activity
• Growth hormone binding protein (GHBP) is produced
Exploratory Pharmacodynamic Markers in Stage Bprotein (GHBP) is produced by enzymatic cleavage from the GH receptor
• Reduction in serum GHBP 5
ALSGHBP
(per protocol population, n=6)
line
levels suggests reduced expression of target GH receptor in ATL1103-treated subjects -10
-5
0 ALSIGF-BP3IGF-II
e fr
om b
ase
j
• Reductions in insulin-like growth factor binding protein 3 (IGF-BP3) and the acid-l bil b it (ALS)
-20
-15
10%
cha
nge
*
*
*labile subunit (ALS) are consistent with the effect of ATL1103 on IGF-I
0 10 20 30Study day
* P-value < 0.05
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ATL1103 Development – Next Steps
Planning for Phase II clinical trial in acromegaly patients underway
• 3 month dosing study in acromegaly patients looking at the level of sIGF-I reduction and normalisation
• Longer and higher dosing than employed in Phase I trail should result in a higher level of accumulation of ATL1103 in the tissues (liver) potentially leading to a more significant pharmacological (sIGF-I reduction) effect
• Hypothesis is that ATL1103 could also have a greater pharmacological effect on sIGF-I levels in acromegalic patients
• Acromegalics have excess levels of GH and therefore have greater receptor occupancy and signaling to produce sIGF-I
• Reducing GHr expression using ATL1103 could have a greater impact on GH g p g g psignaling through GHr and in turn on sIGF-I levels in acromegalics than in volunteers who generally have a surplus of unbound GHr
• Study forecast to commence 1’H’2012 with interim results potentially available early to mid 2013F
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ATL1103 Development – Next Steps (continued)
Potential ATL1103 and Somavert ® combination study
• Data from Phase I study supports opportunity of using ATL1103 and Somavert ® in• Data from Phase I study supports opportunity of using ATL1103 and Somavert ® in combination to exploit the potential synergistic benefits of the combined therapy
• Combination would potentially allow for more Somavert ® to be freed up to bind to more cell surface GHr and thereby increase Somavert ®’s pharmacological activitymore cell surface GHr and thereby increase Somavert s pharmacological activity
• An provisional US patent application has been recently lodged which seeks to provide protection for the use of the drugs in combination until 2033
• Combination could allow Somavert ® to be used at lower/less frequent doses (e.g. once weekly vs current daily dosing) in acromegaly treatment, and other disease areas such as some cancers where a greater reduction in sIGF-I may be required
• The Company is looking at conducting a PoC clinical study to assess the tolerability of the combination and its effect on sIGF-I to confirm that the combination improves on the activity and clinical profile of Somavert ® when used alonealoneF
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ATL1101 for Prostate Cancer
Disease & Market
• Approximately 1 in 6 men will develop prostate cancer
• Disease gradually progresses to metastatic castrate resistant prostate cancer – mostaggressive form: Treatment options are limited and prognosis is poor
Product
• ATL1101 is a 2nd generation inhibitor of IGF-IR (emerging target in oncology)
• IGF-IR inhibition blocks key cell survival/proliferation pathways
• Major Pharma Co’s have mAb programs targeting IGF-IR confirming the attractiveness ofthe target in cancer drug development
Project Status
• Significant suppression of key tumour signalling pathways and prostate cancer tumourgrowth demonstrated in animal studies. Select toxicology studies completed
• Granted an Option to License to Australian Co to further develop ATL1101 subject to Coi f di t ATL1101 i t Ph I/II t i l i t tsecuring funding to move ATL1101 into Phase I/II trials in prostate cancerFor
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ATL1101 enhances Taxol® tumour cell cytotoxicity in vivo
Combination therapy ATL1101 and PaclitaxelFor in vivo study, 2 X 106 PC-3 cells were inoculated s.c. in the flank region of 6-8 week old male athymic nude mice via a 27
ATL1101
ISIS 306064
week-old male athymic nude mice via a 27-gauge needle under methoxyfluoraneanesthesia. When mice bearing PC-3 tumors reached a palpable tumor volume of 200 mm3 they were randomly assigned for treatment with 15 mg/kg IGF-1R ASO (ATL1101) i t h d ODN(ISIS306064)(ATL1101) or mismatched ODN(ISIS306064) once daily for 5 days and three times per week thereafter by i.p. injection. At days 7, 9, 11 and 21, 23, 25, 0.5 mg of micellarpaclitaxel was administrated i.v. once daily. Each experimental group consisted of 10 mice.
Furukawa, Wraight, Monia, Gleave & Cox (2009), presented at 10th National Prostate Cancer Symposium, Melbourne, Australia
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ATL1102 for Multiple Sclerosis
Disease & Market
• Life-long chronic disease of the central nervous systemg y
• Global drug sales of >US$6bn and forecast to grow to US$10bn by 2012
• Need for more effective drug with less side effects
Product
• 2nd generation antisense inhibitor of VLA-4 protein
• VLA-4 is a clinically validated target in MSVLA 4 is a clinically validated target in MS
• ANP completed successful Phase II trial confirming drug activity and safety in MS patients
Project StatusProject Status
• Previously licensed to Major Pharma company now back with ANP
• The Company is seeking a new partner to continue the developmentFor
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ATL1102 Phase II study met primary end-point: reduction in new active lesions
ATL1102 reduced no. of new active lesions by 54.4%, p = 0.01 4.0 Mean +/- SEM
ns 3.0
3.5Plac. ATLCNNAL wk 4, 8 and 12
ATL1102 vs placebo p=0.01
activ
e T2
lesi
o
2.0
2.5
ew T
1-G
d pl
us
1.0
1.5
Ne
0 0
0.5
Treatment Phase
Baseline Week 4 Week 8 Week 12 Week 160.0F
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ATL1102 Stem Cell Mobilization in Cancer
• Bone marrow stem cells are mobilized to the blood for collection before high dose chemotherapy and re infusion N ® (Fil ti ) GCSF i t i th k t l d i SCM• Neupogen ® (Filgrastim) a GCSF agonist is the market leader in SCM • Effective in 35% and 20% of MM and NHL patients respectively in releasing sufficient
numbers of Hematopoeitic Stem cells (HSC) for SCM
S l $ Billi d d t ff t t i 2013 i th US• Sales are $ Billions and product off patent in 2013 in the US
• In 2008 it was estimated that 55,000 patients could benefit from more HSC release including MM and NHL patients
• Mozobil ® (Plerixafor) CXCR-4 antagonist from Genzyme• Approved for use in combination with GCSF for increased HSC release• Registered in the US and in Europe in 2009• Effective in combination with GCSF in achieving sufficient levels of SCM in an
additional ~40% of both MM and NHL patients• ~ $7500 for a single vial for one daily injection• Sales of US$100 million in 2010 with future sales potential forecasted at• Sales of~US$100 million in 2010 with future sales potential forecasted at
~US$300million/annum
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Features of the ATL1102 SCM Mobilization Opportunity
• Acute treatment: ATL1102 in HSC/progenitor release would be a short duration (1 or 2 week) treatment
• Activity demonstrated in Humans: ATL1102 increased CD34 RNA in total blood RNA ofActivity demonstrated in Humans: ATL1102 increased CD34 RNA in total blood RNA of Phase II MS patients at 8 weeks by 1.5 fold v baseline (P< 0.027)
• Early onset of action: in short duration mouse studies an antisense to mouse VLA-4 plus GCSF released 13X more CD34+ progenitor myeloid cells vs 7X more only with GCSF alonealone
• Desirable kinetics: in animals ATL1102 rapidly distributes from the blood to the bone marrow
• Tox studies completed: ATL have completed mouse and monkey systemic safety studiesTox studies completed: ATL have completed mouse and monkey systemic safety studies for human trials
• Safety in humans established: Phase I safety data in volunteers and from Phase II MS patient study
Q i k d i i t t i h i iti l P C t i l i ll b f• Quick and inexpensive to prove concept in humans: initial PoC trial in small number of volunteers to test the drug’s potential to release CD34+ HSCs as the primary endpoint
• Orphan drug indication: regulatory assistance provided makes development more affordable
• Patent protection: patent application seeking protection on SCM to 2031For
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ATL1102 Stem Cell Mobilization in cancer: Market opportunity
Target markets
GCSF + M bil f il i MM d NHL ti t h h ti f t
pp y
• GCSF + Mozobil failures i.e MM and NHL patients who have unsatisfactory level of HSC release with GCSF and Mozobil
• GCSF+Mozobil users where the combination has other therapy limitations t f t t t f t ll ti ie.g cost of treatment, safety, collection regimen
• GCSF failures where ATL1102 proves to have clinically significant advantages over Mozobil
ATL1102 Potential $ Market in SCM
ATL1102 i HSC l h l h d d $ illi k t t ti l lik• ATL1102 in HSC release has several hundred $ million market potential like Mozobil
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Potential Near Term Value Drivers
ATL1103
• Progress of clinical development
• Phase II clinical trial in acromegalics
• Possible ATL1103/Somavert® combination study
• Potential partnering deal
ATL1101
• Potential exercise of Option Agreement and commencement of Phase I/II clinicalPotential exercise of Option Agreement and commencement of Phase I/II clinical trial in prostate cancer patients
ATL1102
• Potential partnering arrangement for continued development of ATL1102 in MS, stem cell mobilisation and asthma
Clinical progress of antisense technology
• Filing of KYNAMRO (mipomersen) US NDA and potential EU approval
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Appendicespp
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ATL1103 - Pre-clinical mouse pharmacology
10 weeks of treatment with a 2nd generation antisense to the mouse GHrreduces serum IGF-I ~60% with the effect sustained 10 days past the last dosereduces serum IGF I 60% with the effect sustained 10 days past the last dose
IGF-I suppression GHr mRNA target inhibition
45% decrease; p<0.005ml)
at d
ay 7
(ng/
seru
m IG
F-I a
s
Tachas, Lofthouse, Wraight, Waters et al. J Endocrinol 189, 147-54 (2006).
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ATL1103 Active in Mice
3 weeks of ATL1103 treatment reduces serum IGF-I >55% (to below detection)
IGF-I suppression GHr mRNA target inhibition
ng/m
l) 55% decrease; p<0.005
day
22 &
26
(um
IGF-
I at d
Data on File:
seru
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ATL1103 - Pre-clinical mouse pharmacology
GHr antisense reduced retinal neovascularization more than octreotide (38% vs 26%) Wilkinson-Berka et al: Mol Vis 13, 1529-38 (2007)
Inhibition of retinal neovascularisation*P<0.0001 compared to all sham groups.#P<0 0005 d t OIR hi l
25
30
35 **#
*#
#P<0.0005 compared to OIR +vehicleX = 38% reduction vs vehicle control+ = 26% reduction vs vehicle control
OIR (ROP)
5
10
15
20
25 *#
*# XSham RoP
0
5
sham 5mg 10mg 20mg 30mg ROP 5mg 10mg 20mg 30mg
ATL227446 dose / kg body weight, i.p.Octreotide dose / kg body weight, i.p bi-dailyFor
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ATL1103 Active in Primates
• Pharmacologically relevant suppression of circulating IGF-I• Significant suppression of hepatic target mRNA, IGF-I mRNA and serum IGF-I• No increase in circulating GH observed• Pharmacological paradigm demonstrated in normal primates
IGF-I suppression GHr mRNA target inhibition
Antisense Therapeutics Ltd data on fileFor
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ATL1101 systemic delivery: Effects on LNCaP and PC-3 tumours in vivo
* **
*
**
*
* ** *
A, LNCaP cells were inoculated s.c. and when PSA values exceeded 50 ng/ml, mice were castrated and randomly selected for treatment with ATL1101 or control ODN (15 mg/kg) injected i.p. once daily for 7 days and 3 times per week thereafter.B, blood samples were obtained from the tail vein of the mice once weekly to measure serum PSA by ELISA.C PC 3 ll i l t d d h t h d 100 3C, PC-3 cells were inoculated s.c. and when tumors reached 100 mm3, mice were randomly selected for treatment with the same protocol as LNCaP. Each point represents the mean tumor volume in each group containing 10 mice;bars, SE. * differs from control ODN treatment group (p < 0.05) by Student’s t test.
**
**
In LNCaP xenografts, ATL1101 significantly delayed the tumor growth and PSA rise rates after castration.In PC3 xenografts, ATL1101 monotherapy significantly reduced tumor volume compared to the mice treated with control ODN (ISIS306064).
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ATL1101 activity in taxane-resistant prostate cancer cells:ATL1101 retains cytotoxicity & re-sensitises to Taxol® effects in vivo
For in vivo xenograft studies, 2 x 106 either parental PC3 or PtxR PC3 cells were inoculated s.c. in the flank of 6-8 week-old male athymic nude mice.When tumors reached 200 mm3 mice were randomly selected for treatmentWhen tumors reached 200 mm , mice were randomly selected for treatment with 15 mg/kg ATL1101 or control oligonucleotide (ISIS 306064) injected i.p. once daily for 7 days and 3 times per week thereafter.For combination setting with paclitaxel, at days 7, 9, 11 and 21, 23, 25: 0.5 mg of paclitaxel was administered i.v. once daily.Each experimental group consisted of 10 or 11 mice.T l t f d kl
Antisense Therepautics Ltd. proprietary data on file
Tumor volume measurements were performed once weekly.For
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Inhaled ATL1102 for Asthma
Sub-µg/kg inhaled doses of mouse VLA-4 antisense drug (“ASO”) suppress OVA-induced airway hyperresponsiveness compared to control oligonucleotide
drug (“control oligo”)drug ( control oligo )
*P 0.05 vs. Vehicle
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