INVION LIMITED — Investor Presentation 2014

Jun 5, 2014

Invion Limited (ASX:IVX) Clinical-stage life sciences company targeting chronic inflammation

Investor Presentation June | 2014

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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.

Invion: targeting inflammation

3 drug candidates in development

Developing two new respiratory franchises

• INV102 (nadolol) : beta-blocker being repurposed to treat inflammatory airway diseases including COPD and cystic fibrosis

• INV104 (zafirlukast) : anti-leukotriene being developed as inhaled product for treatment of asthma

An early partnering opportunity

• INV103 (ala-Cpn10) : modified, naturally occurring human protein for the treatment of autoimmune diseases

• 3 FDA-regulated phase II clinical trials currently underway

• Collaborating with 3M on inhaled respiratory franchise

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3

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Targeting respiratory disease INV102 (nadolol) - unique beta-blocker INV104 (zafirlukast) - leukotriene receptor antagonist

Spectrum of airway disease and opportunities

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Global market size: $34B $2.4B $1.2B
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Exercise
Mild Moderate Severe Chronic Smoker’s Cystic
Induced
Asthma Asthma Asthma Bronchitis cough Fibrosis
Asthma
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Zafirlukast

Monotherapy + combinations

Nadolol

Monotherapy + combinations

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Professor Richard Bond, PhD, Professor of Pharmacology, University of Houston (USA)

• Early work provided functional evidence for a beta-adrenoceptor - eventually found to be the beta3-adrenoceptor

• In collaboration with Nobel Prize winner R. J. Lefkowitz and others, undertook studies on the spontaneous activity of G-protein-coupled receptors and compounds

• Research has focussed on paradigm shift that occurred with regard to the use of beta-blockers in the treatment of congestive heart failure, and whether a similar phenomenon could be applicable in asthma therapy

• The work of Professor Bond and collaborators has been published in top scientific journals including Nature, Science, and the Proceedings of the National Academies of Science

• “All beta-blockers are not created equally; the unique profile of INV102 (nadolol)”

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Background

Beta-Agonists are approved for the treatment of asthma

• Acutely, Beta-Agonists are potent bronchodilators, but

chronic use can cause loss of asthma control and an increase asthma related mortality

• Beta-Blockers are contraindicated for the treatment of

asthma

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The critical role of the epithelium in the phenotype of severe airway disease

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Asthma

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COPD

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8 y.o. girl treated at Texas Medical Centre

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Cystic Fibrosis

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Validity of the preclinical murine model

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Control
mouse
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‘Asthmatic’
mouse
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β2-adrenoceptor signaling pathways

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ligand
The canonical cAMP-dependent New pathway discovered ~2000
pathway (Lefkowitz)
βarrestin
Adenylyl cyclase
Activation of MAPKs
cAMP-accumulation
(ERK)
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Effects of different beta-blockers on mucous in mouse asthma model

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Alprenolol

Carvedilol

INV102 (nadolol)

Proof of concept has been achieved in pre-clinical studies with inhaled INV102

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Nadolol is different from other beta-blockers

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100
Epinephrine
80
60
Carvedilol
40 Alprenolol
Propranolol
20
INV102 (nadolol)
0
-0.004 -0.003 -0.002 -0.001 0.001 0.501 1.001
ERK1/2 activation
Beta arrestin signaling
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Rate of cAMP accumulation

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Alprenolol

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ligand
β2 adrenoceptor
cAMP-dependent βarr-dependent
pathway pathway
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Carvedilol

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ligand
β2 adrenoceptor
cAMP-dependent βarr-dependent
pathway pathway
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Carvedilol and alprenolol did not work

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ligand
β2 adrenoceptor
cAMP-dependent
βarr-ERK pathway
pathway
Asthma
phenotype
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Nadalol (acute)

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ligand
β2 adrenoceptor
cAMP-dependent βarr-dependent
pathway pathway
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Nadolol (chronic)

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ligand
β2 adrenoceptor
?
cAMP-dependent βarr-dependent
pathway pathway
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Nadolol is different from other beta-blockers

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100
Epinephrine
80
60
Carvedilol
40 Alprenolol
Propranolol
20
INV102 (nadolol)
0
-0.004 -0.003 -0.002 -0.001 0.001 0.501 1.001
ERK1/2 activation
Beta arrestin signaling
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Rate of cAMP accumulation

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Conclusions

The β2 adrenoceptor has two signaling pathways

Beta-blockers can act at the two pathways in different ways

• Their signaling determines their efficacy in asthma

• INV102 (nadolol) is beneficial in mouse asthma models

• other beta-blockers are not

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Mitchell Glass, M.D., Executive VP R&D and Chief Medical Officer

• 5 FDA approved drugs

• Managed more than 40 drug developments including “first in class”

• Led development of beta blocker carvedilol (Coreg)

• Led development phases I - III of oral zafirlukast (Accolate)

• Board certified pulmonary and critical care specialist

• 25 year veteran of Pharma (AZ, GSK) and Biotech (AGIX)

• Leads Invion’s experienced clinical development team

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INV102 (nadolol)

Clinical data to date

  - Two phase II clinical trials completed

     - Safety profile enhanced by titration starting at very low doses

     - > Dose-related reduction of airway hyper-responsiveness

• Goals of oral INV102 (nadolol) program

• Asthma program (phase II) is NIH funded; follow-on study could target severe asthma

• Smoking cessation program is a ‘speed to market’ opportunity; proprietary titration strategy and dose strengths

• Invion / 3M collaboration accelerates inhaled program

• Inhaled INV102 targeted to treat COPD and cystic fibrosis

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Medical, regulatory and commercial precedent

Precedent: Chronic Heart Failure (CHF)

FROM

CONTRAINDICATED Warning against use of beta blockers in CHF for > 25 years. Carvedilol annual sales (1998) $40m

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TO

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)

Invion target: Chronic Obstructive Pulmonary Disease (COPD)

FROM CONTRAINDICATED Warning against use of beta blockers in COPD for > 25 years. Nadolol current sales: $ nominal (generic)

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TO

STANDARD OF CARE After careful titration, beta blocker INV102 (nadolol) targeted to reduce airflow obstruction due to damaged airways. Target: First in class

NOTE: The effect of INV102 (nadolol) on airways cells is unique among β blockers. β1 success in the heart (CHF) mitigates the risk of β2 success in the lung (COPD)

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INV102: phase II trial design - mild asthma

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INCLUSION ORAL DOSING WITHDRAWAL ENDPOINTS
26wks 4wks
Randomised Efficacy
Controlled Nadolol Treatment Improved
Clinical Trial Titration & Tolerability Placebo airway hyper-
(N=30, 1:1 Placebo: Active) responsiveness
Safety
Titration and
N=60
bronchoscopy
Bronchoscopy Substudy
Placebo tolerated over
(n=30, 1:1 Placebo: Active)
Mild persistent
6 mo dosing
asthma
NIH Sponsored NCT:01804218
Randomize
Randomize
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NCT:01804218

PI & Protocol Chair: Nicola Hanania, MD Active clinical trial sites include:

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INV102: phase II trial design - smoking cessation

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INCLUSION ORAL DOSING WASHOUT ENDPOINTS
11-15wks 2wks
E
Randomised Primary
(IWRS) 50% Decrease in # of O
Nadolol Treatment (n=65)
Controlled dose P
cigarettes per day
3wks titration &
Clinical Trial each
II
during last 28 days
5-8wks maintenance week
M
Safety
E
Change in FEV1,
N=130 E
exacerbations,
Placebo Control (n=65) T
adverse events
Failed to quit
“titration” & maintenance I
+ COPD
N
and
G
chronic cough
NCT:01825122
Placebo
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PI: Mario Castro, MD Active clinical trial sites include: Birmingham, Alabama

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INV102 (nadolol): oral program

Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic receptor biased ligand Completion Asthma oral program, ongoing phase II study 2Q15 EOP2 Smoking cessation oral program, phase II interim and final data and EOP2 commence ph III 4Q14

Airway inflammation

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Respiratory therapeutics: inhaled program INV102 (nadolol) in COPD & cystic fibrosis INV104 (zafirlukast) in asthma

Recent capital raise and development collaboration allow acceleration of clinical development

Collaboration with 3M Drug Delivery systems

Inhalation development expertise

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Proprietary formulation and device

Works will assess the feasibility of inhaled INV102 (nadolol) and INV104 (zafirlukast) delivered using 3M’s proprietary pressurised metered dose inhalation (pMDI) technology

Collaboration encompasses manufacture for toxicology and phase I studies

• 50% of all MDIs worldwide use 3M technology

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INV102 (nadolol): comparison oral vs inhaled

Target Product Profile

Oral Inhaled

• IP protection: titration and method of use (USA)

• IP protection based on 3M formulation and device

• Once daily dosing including titration to avoid

systemic side effects

• Once daily dosing with no need for titration and no systemic side effects

• Invion phase II and III data limited to 13 weeks for smoking cessation

• Safe for long term regular use for chronic airway diseases

> New indication limited to smoking cessation

• Approved for long term use in COPD, severe asthma and cystic fibrosis

• No efficacy data on concomitant use of inhaled corticosteroids (severe asthma) or antibiotics

(CF)

• Safety and efficacy data in combination with LABA + ICS (Asthma), antibiotics (CF), and LAMA + ICS (COPD)

• Limited data on reducing cough, sputum

• Indicated for reducing cough, sputum production,

production, “smoker’s cough”, avoiding use of

• “smokers’ cough”, decreasing use of steroids or

steroids or preventing/ameliorating

preventing/ameliorating exacerbations

exacerbations

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INV102 (nadolol): inhaled program

Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic receptor biased ligand Completion Asthma oral program, ongoing phase II study 2Q15 EOP2 Smoking cessation oral program, phase II interim and final data and EOP2 commence ph III 4Q14 Pre IND COPD inhaled monotherapy: formulation and development pre-IND, commence ph I 1Q15 feasibility: inhaled Asthma monotherapy + ICS feasibility: inhaled Cystic fibrosis monotherapy + antibiotic

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Invion: 3 drugs in development

Developing two new respiratory franchises

INV102 (nadolol) : beta-blocker being repurposed to treat inflammatory airway diseases including COPD and cystic fibrosis

• INV104 (zafirlukast) : anti-leukotriene being developed as inhaled product for treatment of asthma

An early partnering opportunity

• INV103 (ala-Cpn10) : modified, naturally occurring human protein for the treatment of autoimmune diseases

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Pipeline: 12-18 month outlook

Airway inflammation 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic receptor biased ligand Completion Asthma oral program, ongoing phase II study 2Q15 EOP2 Smoking cessation oral program, phase II interim and final data and EOP2 phase III commenced 4Q14 Pre IND COPD inhaled monotherapy: formulation and development phase I commenced 1Q15 feasibility: inhaled Asthma monotherapy feasibility: inhaled Cystic fibrosis monotherapy INV104 (zafirlukast) = leukotriene receptor antagonist IND, phase I IND Asthma inhaled monotherapy: formulation and development commenced 2Q15 feasibility: inhaled Asthma

Airway inflammation

IND, phase I IND commenced 2Q15 feasibility: inhaled combination therapy

Autoimmune disease

INV103 (ala-Cpn10) = modified natural human protein Lupus (SLE) completion ph II study, IV/SC bridging study Partner Partner

Lupus (SLE)

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Summary

 3 drug assets with multiple paths to market  early partnering opportunity for INV103 (ala-Cpn10)  3 FDA-regulated phase II clinical trials  two de-risked novel and proprietary inhaled respiratory assets  collaboration with global partner on inhaled franchise  experienced management team  significant valuation drivers: 12-18 months

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Dr Greg Collier Managing Director and CEO Invion Limited

GPO Box 1557 Brisbane, QLD, 4001 Australia

P: +61 7 3295 0500 E: greg.collier@inviongroup.com W: www.inviongroup.com

Investor Presentation June | 2014