dr greg collier presents invion at asiabiotech for ... · ceo chemgenex pharmaceuticals (sold to...
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MARKET ANNOUNCEMENT
Invion Limited ABN 76 094 730 417
Unit 2, 120 Bluestone Circuit, Seventeen Mile Rocks, QLD 4073 P +61 7 3295 0500 F +61 7 3295 0599 www.invion.com.au
MARKET ANNOUNCEMENT
Dr Greg Collier presents Invion at AsiaBiotech
BRISBANE, 3 JUNE 2013: Australian drug development company Invion Limited (ASX: IVX) is
pleased to release a copy of the presentation that Managing Director and CEO, Dr Greg Collier will
deliver this week during investor meetings in Singapore and Hong Kong, and to the
AsiaBiotech Invest conference.
The conference presentation will occur on Wednesday 5 June at 12:05pm, local time at the
Sheraton Hotel and Towers, Hong Kong.
Dr Collier will provide an overview of the Company's current activities, including:
• phase II clinical trials of INV102 (nadolol) in asthma and chronic bronchitis;
• the phase II development of INV103 (ala-Cpn10) as a potential therapy for lupus; and,
• Invion's expected value drivers over the next 12 - 36 months
Information about the AsiaBiotech Invest 2013 conference can be found at
http://asiabiotechinvest.com.
About Invion Limited
Invion Limited (ASX:IVX) is a life sciences company with two drug assets in three FDA-regulated, phase II clinical
programs. With operations in the US and Australia, the strategic focus of IVX is the development of treatments for
major market opportunities in inflammatory diseases, including asthma and COPD ($34B) and lupus (to $4B).
The company’s corporate focus is the cost-effective advancement of its assets to late phase II before negotiating
commercial partnerships.
INV102 (nadolol) is a beta blocker that has been used in more than 10 million people for the treatment of high
blood pressure, migraine and chest pain. Invion is repurposing INV102 to treat lung indications and to date the
company has completed two phase II clinical trials which demonstrated acceptable safety as well as dose-related
reduction of airway hyper-responsiveness. A further phase II trial in asthma - funded by the US National
Institutes of Health in excess of $4 million - is now underway, and a trial in chronic bronchitis patients is due to
commence. INV103 (ala-Cpn10) is a modified naturally occurring human protein that has shown to reduce IL-6,
a key marker in the inflammatory disease, lupus. A phase II trial in lupus is anticipated to commence in Q2 2013,
under a US IND submitted 24 April 2013.
FOR MORE INFORMATION CONTACT:
Investor Relations: Rebecca Wilson, Buchan Consulting P: 03 9866 4722 [email protected]
Media Relations: Jane Lowe, Buchan Consulting P: 02 9237 2807 [email protected]
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Invion Limited (ASX:IVX)
Clinical-stage life sciences company targeting chronic inflammation
Corporate Presentation June | 2013
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Disclaimer This presentation has been prepared by Invion Limited (Invion or the Company) solely for its use at presentations to
be made by the Company. The information contained in this presentation is an overview and does not contain all
information necessary to make investment decisions. Although reasonable care has been taken to ensure that facts
stated in this presentation are accurate and that the opinions expressed are fair and reasonable, no representation,
expressed or implied, is made as to the fairness, accuracy, completeness or correctness of the information and
opinions contained in this presentation and no reliance should be placed on such information or opinions. This
presentation does not constitute an offer, invitation, solicitation or recommendation with respect to the purchase or
sale of any security in the Company nor does it constitute financial advice nor take into consideration your investment
objectives. This presentation contains or may contain forward-looking statements that are based on management’s
belief, assumptions and expectations and on information currently available to management. All statements that are
not historical, including those statements that address future operating performance and events of developments that
we expect or anticipate will occur in the future, are forward looking statements. Although management believes these
forward looking statements are fair and reasonable you should not place undue reliance on these statements.
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Invion proposition
> Two phase II proprietary therapeutic candidates that target chronic
inflammation
> INV102 (nadolol) (chronic bronchitis, asthma, cystic fibrosis)
> INV103 (ala-Cpn10) (lupus)
> Advancing clinical-stage company with reduced clinical risk
> Experienced and well credentialed Board and international KOL
networks
> Experienced management team with significant FDA experience
> Existing NIH linkage grants with scope for additional non-dilutive
capital
> Significant valuation drivers: from 12 months - 3 year horizon
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Experienced management team
Greg Collier, PhD., MD and CEO
> 20 year career in pharma research, development and commercialisation.
CEO ChemGenex Pharmaceuticals (sold to Cephalon $230M). 150 peer reviewed
publications, 33 patents, Roche Award for Excellence.
Mitchell Glass, M.D., EVP R&D and CMO
> 25 year veteran of Pharma (AZ, GSK) and Biotech (AGIX). Managed more than 40
drug developments including “first in class” and beta blocker carvedilol (Coreg). 5
FDA approved drugs.
James Campbell, PhD., Executive Director
> 20 years international research, management and venture capital experience.
COO and CFO ChemGenex Pharmaceuticals. Member of two VC investment
committees and commercialization advisor to several universities.
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Pipeline: three phase II trials underway in 2013
Preclinical Phase I Phase II
INV102 (nadolol)
INV103 (ala-Cpn10)
New chemical entity
Asthma
Chronic Bronchitis
Lupus (SLE)
INV102 (nadolol)
Chronic bronchitis
Cystic fibrosis
NIH funded, US$4m+ non-dilutive funding (oral delivery)
In patients undergoing smoking cessation (oral delivery)
Large unmet medical need
Inhaled program
Inhaled program
Academic alliance Beta-2 adrenergic
inverse agonist
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INV102 (nadolol) • existing drug being repurposed for a new target
• aim to develop an inhaled drug for the treatment of respiratory
diseases including asthma and COPD
• short term path to commercialisation with oral treatment of COPD
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INV102 (nadolol)
> An inverse -agonist
> block agonist stimulation of the receptor; AND,
> inactivate intracellular inflammatory events that are stimulated spontaneously
or by agonists
> Current indications: high blood pressure, chest pain, migraine
> Being repurposed to treat: inflammatory lung conditions
> Suite of patents granted and in prosecution
Data to date
> Preclinical data confirms nadolol:
> As adrenergic inverse agonist providing unique anti-inflammatory activity
> Possesses unique activity to protect airway or reverse mucus metaplasia
> Two phase II clinical trials completed
> 80% positive response against objective endpoint
> acceptable safety
> dose-related reduction of airway hyper-responsiveness
References: Bond et al. ‘Complementary anti-inflammatory effects of a -blocker and a corticosteroid in asthma’ Arch
Pharmacol 2011
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Significant market opportunity
References: Respiratory and Inflammation, AstraZeneca Annual Report, 2011; Smoking Cessation Drugs: World Market
Prospects 2012-2022, Visiongain Reports 2012 ; Healthcare Finance, Bloomberg Brief, 13 August 2012; Full-Year and
Fourth-Quarter 2011 Financial Results, Merck & Co. * Company estimates
Respiratory world market $
21.6B
12.9B 8.4B
21.7B
> Prescription respiratory world market $64.6B
> Asthma and COPD prescription drugs $34B
> Advair Diskus ® (asthma and COPD) $8.1B
> Singulair ® (asthma) $5.5B
> Symbicort ® (asthma and COPD) $3.1B
> FDA Black box warning on all Long
Acting Beta Agonists (LABAs) and
LABA/Steroid combinations:
increased risk of death
> Smoking cessation drug market $2.4B
> Nicotine replacement therapy (NRT) is
bulk of existing market - does not address
lung healing
> 10-15% of early failures due to cough
associated with excess mucus*
> Opportunity to expand existing market
Asthma COPD
Rhinitis Other
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INV102: Mechanism of action
> Healthy lung tissue consists of
mostly ciliated epithelial cells with
smaller numbers of (secretory)
goblet cells
> In disease states the proportion of
goblet cells increases, lining the
lung with a “mucous plug” that
impairs gas transfer
> Further, smooth muscle cells
spasm causing bronchoconstriction
Ciliated epithelia Goblet cell
Airspace
Airway surface liquid
Smoking Asthma
Mucous plug
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Mechanism of action targets multiple pathways
> Reduction of goblet cell metaplasia
> Reduced mucous hypersecretion
> Restoration of ciliated epithelium
> Reduced levels of pro-inflammatory
cytokines: IL-5, IL-10, IL-13
> Down-regulation of bronchoconstriction:
> 2x Phospholipase Cb
> 6x Phosphodiesterase 4d
> 50% reduction in eosinophils
> Restoration of lung function
Ciliated epithelia Goblet cell
Airspace
Airway surface liquid
Mucous plug
Healing INV102
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Preclinical studies demonstrate airway healing
Proof of concept has been achieved in pre-clinical studies with inhaled INV102
Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model. Nguyen et al. Am J
Respir Cell Mol Biol. 2008 Mar;38(3):256-62. See also. β-Adrenoceptor signaling is required for the development of an asthma
phenotype in a murine model. Nguyen et al. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2435-40.
Control lung tissue Lung tissue of ‘asthmatic’ mice treated
with INV102 (nadolol) for 28 days:
restored epithelium
Lung tissue of ‘asthmatic’ mice: epithelial
cells have been converted to mucus-
producing goblet cells. No effect on
alprenolol
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Successfully completed two phase II clinical trials
Objective: Proof-of-concept to evaluate safety and effects on airway with escalating doses
administered to 19 subjects with mild asthma
Primary endpoint: Objective measure of airway hyper- responsiveness (PC20 MeChFEV1),
the diagnostic hallmark of asthma
Key Findings: Led NIH to fund phase IIb study in asthma:
> Safety: well tolerated in doses up to 40mg
> Efficacy: airway hyper-responsiveness:
> dose response with ineffective dose at 10mg/day
> 9 -10 weeks of treatment produced a dose-dependent decrease in airway hyper-
responsiveness that achieved clinically significant improvement
> Lung function:
> attenuation of first dose decrease in FEV1 by titration
> same benefit and commercial strategy as Coreg in CHF
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INV102: Clinical strategy Oral programs support development of inhaled product
Preclinical Phase I Phase II
Oral program
Asthma
Chronic Bronchitis
Inhaled program
Chronic bronchitis
Cystic fibrosis
NIH funded, US$4m+ non-dilutive funding
In patients undergoing smoking cessation
Oral data supports strategy
Large unmet clinical need
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Medical, regulatory and commercial precedent Precedent: Chronic Heart Failure (CHF)
Invion target: Chronic Obstructive Pulmonary Disease (COPD)
CONTRAINDICATED
Warning against use of
beta blockers in CHF for > 25 years.
Carvedilol annual sales (1998) $40m
STANDARD OF CARE
After careful titration, beta blocker
Carvedilol reduced mortality in
all classes of CHF
First in class: Carvedilol peak annual
sales $1.5 BILLION (2010)
FROM TO
CONTRAINDICATED
Warning against use of
beta blockers in COPD for > 25 years.
Nadolol current sales: $ nominal
(generic)
STANDARD OF CARE
After careful titration, beta blocker
INV102 (nadolol) targeted to reduce
airflow obstruction due to damaged
airways.
Target: First in class
FROM TO
NOTE: Nadolol effect on airways cells is unique among β blockers
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Trial name INV102 (nadolol) in smoking cessation of patients with pre-existing COPD
Trial design Double-blinded, randomised, placebo-controlled
Patients 130 (65 per arm: 54 needed for analysis)
Timing Start Q2 2013 Initial data Q4 2013
Inclusion criteria Previously failed to quit, have COPD and chronic cough
Principal Investigator Dr Albert Rizzo, Chief of Pulmonary and Critical Care Medicine, Christiana Care;
Past Chair (2011-12) American Lung Association
Site Christiana Care (Wilmington, Delaware)
Doses 1.25mg, 2.5mg, 5mg, 10mg, 25mg, 50mg (dose titration)
Primary endpoints Abstinence from smoking in last 2 weeks of trial
Secondary endpoints Number of cigarette-free days; clinical COPD questionnaire; MMRC Dyspnea
Scale; markers of COPD; sputum markers of COPD
Safety endpoints Change in FEV1; requirement for rescue medication; COPD exacerbation rate
Comment Data will support broader oral and inhaled development program
Regulatory Status www.clinicaltrials.gov ID: NCT01825122
INV102: phase II trial design – smoking cessation F
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INV102: phase II trial design – mild asthma
Trial name INV102 (nadolol) in mild asthma (NIMA)
Trial design Double-blinded, randomised, placebo-controlled, multi-centre
Patients 60 subjects (30 subjects in each of two treatment arms)
Timing Start Q1 2013 Finish 2015
Inclusion criteria Mild asthma: only β agonists as needed
Principal Investigator Nicola A. Hanania, M.D., M.S., Baylor College of Medicine
Sites Baylor, Washington University, Duke University
Doses 1.25mg, 2.5mg, 5mg, 10mg, 25mg, 50mg (dose titration)
Primary endpoints Improved airway hyper-responsiveness via change in methacholine PC20 (based
on FEV1)
Safety endpoints Safety of titration and 6 months’ dosing
Exploratory endpoints Reduced airway inflammation and mucous metaplasia; increased β2AR density,
affinity and signaling in airway epithelial cells; change in exhaled (eNO)
Comment Clinical program under US IND (submitted Feb ’07)
Regulatory Status www.clinicaltrials.gov ID: NCT01804218
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INV102: phase II milestones
Asthma
> An NIH funded phase II study ($4.4 million non-dilutive funds) was initiated Q1
2013
> Initial data obtained Q1 2014 on airway histology and sputum biomarkers
> Completed phase II data anticipated 2015
> Target outcomes: improve airway hyper-responsiveness, reduce airway
inflammation and mucus metaplasia
Chronic bronchitis (smoking cessation)
> Phase II initiation anticipated Q2 2013
> Target outcomes: increase smoking cessation, reduce airway inflammation,
decrease peri-operative complications
> Initial data obtained Q4 2013 – sputum and smoking cessation
> Data will support broader oral and inhaled development program
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INV103 (ala-Cpn10) • modified natural human protein targeting inflammatory disease
• demonstrated anti-inflammatory and immunoregulatory activity
in multiple indications
• strong safety profile
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INV103 (ala-Cpn10)
> Modified version of human Chaperonin 10
> Cpn10 has demonstrated anti-inflammatory and immuno-regulatory activity in a variety of
contexts
> Activity ideally suited to the treatment of inflammation associated with autoimmune
disease
> Data to date
> Dose response reduction in biomarkers of inflammation including serum IL-6, MCP1,
TNF and IL-1
> Strong safety profile >250 patients
> Subcutaneous and intravenous dosing data
> Intellectual Property position
> Composition of matter protection in all the major markets
> US protection to 2026
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Significant market opportunity
> March 2011 FDA approved the first new drug for lupus in more than 50 years
> Reflection of the complexity of the disease
> Clear indication of a major unmet clinical need
> Forecast: sales of over $4B in the US and five major EU markets by 2020
References: Datamonitor: Systemic Lupus Erythematosus Market Forecast, 22 August 2011; Decision Resources:
Systemic Lupus Erythematosus, 2012
0
1000
2000
3000
4000
2007 2011 2020
Lupus market size ($millions)
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INV103: Mechanism of action
> Chaperonins play roles unrelated to protein folding, incl. interplay with
cells involved in the innate and adaptive immune responses
> Expression of Cpn10 is up-regulated in response to inflammation and
can be measured extra-cellularly
> Cpn10 has demonstrated anti-inflammatory and immunoregulatory
activity in a variety of contexts
> Cpn10 is proposed as a ‘resolution-associated molecular patterns’
(RAMPs) molecule
> RAMPs exist in a healthy system to regulate the inflammatory response
> RAMPs activity generates signals which restore immune homeostasis
by deactivating cells with inflammatory phenotypes and expanding
regulatory cells
References: Resolution-associated molecular patterns (RAMPs) in the acute inflammatory response. Inflammation initiates the
over-expression and release of RAMPs, such as Cpn10 (Hsp10). These help limit and resolve the inflammatory responses via
a variety of direct and indirect mechanisms. (Shields A.M., et. al., 2011, Clin and Exp. Immunology, 165, 292-300)
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INV103: Pre-clinical results in lupus models
> Strong pre-clinical data in lupus animal model
(3 studies)
> significantly reduced kidney pathology
> improved survival
> prevented cutaneous lupus
> reduced renal and circulating levels of key
pro-inflammatory mediators (TNF-α, IL-6
and MCP-1) reduced CD4+ T cells and
auto-reactive T cells and increased the
number of activated DC (critical in the
establishment of self tolerance)
> Cpn10 also binds nucleic acid-based ligands
(e.g. DNA, RNA) implicated in SLE
> may be a mechanism for removing altered
self-molecules that activate and perpetuate
the inflammatory response in these patients
Untreated Cpn10 treated
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Systemic lupus erythematosus (SLE or lupus)
> Lupus is a vascular inflammatory disease
> IL-6 is a marker of vascular inflammation
> INV103 has a significant effect on IL-6
> Pre-IND meeting with US FDA Dec 12
> FDA confirmed lupus as important unmet clinical need
> Also confirmed IL-6 as useful marker for dose-ranging
> IND submission April 13 and phase II trial commencement June 13
> Target outcomes: safety in lupus patients, reduction of IL-6 in lupus
patients, improvement in lupus activity, PK to support future increased
dosing
INV103: Phase II clinical strategy F
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Trial name INV103 (ala-Cpn10) in mildly active Systemic Lupus Erythematosus (SLE)
Trial design Double-blinded, randomized, placebo-controlled, intravenous dosing
Patients 32 subjects (8 subjects per dose cohort, 4 cohorts)
Timing Start Q2 1013 Initial data Q4 2013
Inclusion criteria Mild lupus without clinical kidney disease
Principal Investigator Alan Kivitz, M.D., Altoona Center for Clinical Research
Sites Altoona, Pennsylvania; Dallas, Texas
Doses 10 mg - 300mg twice weekly
Primary endpoint Reduction from baseline serum IL-6 levels
Safety endpoints Safety and toxicity; pharmacokinetics; assessment of anti-drug antibodies
Exploratory endpoints SELENA-SLEDAI score (disease activity index); pharmacodynamics; markers of
systemic inflammation and vascular damage
Comment Clinical program under US IND (submitted April 2013)
Regulatory Status www.clinicaltrials.gov ID: NCT01838694
INV103: Phase II trial design – SLE F
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INV103: Phase II milestones
Lupus
> Q4 2013 completion of 1 or 2 cohorts: biochemical evidence of efficacy; safety
of increased doses
> Driver for scale manufacture of ala-CPN10
> Driver for full scale dose ranging in Lupus
> Optional: proof of concept in psoriasis with higher doses from first study
> H1 2014
> INV103: Second study (SLE)
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Summary 2 drug assets
3 FDA-regulated phase II clinical trials
experienced management team
significant valuation drivers: 12-36 months
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Pipeline: three phase II trials underway in 2013
Preclinical Phase I Phase II
INV102 (nadolol)
INV103 (ala-Cpn10)
New chemical entity
Asthma
Chronic Bronchitis
Lupus (SLE)
INV102 (nadolol)
Chronic bronchitis
Cystic fibrosis
NIH funded, US$4m+ non-dilutive funding (oral delivery)
In patients undergoing smoking cessation (oral delivery)
Large unmet medical need, 1 FDA approved drug in 50 years
Inhaled program
Inhaled program
Academic alliance Beta-2 adrenergic
inverse agonist
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Milestones to watch
2013
Q1 Asthma - phase II study in asthma initiated, enrollments and patient dosing underway
Q2 Lupus - IND filed with FDA
> Lupus - initiation of clinical trial and first patients dosed
Q3 > Chronic bronchitis (smoking cessation) - initiation of phase II study
Q4
> Asthma - enrolments completed for phase II trial
> Asthma - early signal of activity expected with secondary endpoints from sputum samples and inflammatory markers
2014
Q1 > Asthma - clinical signals from asthma study in Q1 2014
Q2 > Inhaled program - development of inhaled INV102 (nadolol) complete
> Lupus - interim (cohort) phase II results For
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Summary
2 drug candidates targeting chronic inflammatory diseases
− INV102 (nadolol)
− INV103 (ala-Cpn10)
3 FDA-regulated phase II programs underway in 2013
− asthma
− chronic bronchitis (smoking cessation)
− lupus
Large and growing markets
Data to support strategy
− medical, regulatory, commercial precedent
− phase II clinical trials already completed
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Corporate snapshot
Sector Life Sciences (Biotechnology)
Principal activities Clinical-stage pharmaceutical drug development
Pipeline 2 drug candidates in 3 phase II clinical programs
Operations USA & Australia
ASX code IVX
Share price (31 May 2013) $0.041 (4.1 cents)
Shares on issue ~409.4M
Options on issue ~23M
Market cap (30-Apr-13) ~$16.7 million
Cash at bank (31-Mar-13) $2.07 million
Cash burn (9 months to 31-Mar-13) ~$4.4 million For
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Contact: [email protected]
Invion Limited
2/120 Bluestone Circuit
Seventeen Mile Rocks
QLD 4073 Australia
P: +61 7 3295 0500
F: +61 7 3295 0599
W: www.invion.com.au
Managing Director and CEO
Dr Greg Collier
Investor and Media Relations
Buchan Consulting
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