Slide 1: Invion Limited Investor Presentation
For personal use only Invion Limited (ASX:IVX) Clinical-stage life sciences company targeting chronic inflammation Investor Presentation June | 2014
Slide 2: Disclaimer
For personal use only 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 investmen
Slide 3: Invion: targeting inflammation
Invion: targeting inflammation For personal use only > 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 bein
Slide 4: Targeting respiratory disease
For personal use only Targeting respiratory disease INV102 (nadolol) - unique beta-blocker INV104 (zafirlukast) - leukotriene receptor antagonist
Slide 5: Spectrum of airway disease and opportunities
Spectrum of airway disease and opportunities For personal use only Global market size: $34B $2.4B $1.2B Exercise Mild Moderate Severe Chronic Smoker’s Cystic Induced Asthma Asthma Asthma Bronchitis cough Fibrosis Asthma Zafirlukast Nadolol Monotherapy + combinations Monotherapy + combinations 5
Slide 6: Professor Richard Bond, PhD, University of Houston
Professor Richard Bond, PhD, Professor of Pharmacology, University of Houston (USA) For personal use only > 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
Slide 7: Background
Background For personal use only > 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 7
Slide 8: The critical role of the epithelium in severe airway disease
The critical role of the epithelium in the phenotype of severe airway disease For personal use only Asthma COPD 8 8 y.o. girl treated at Texas Medical Centre Cystic Fibrosis
Slide 9: Validity of the preclinical murine model
Validity of the preclinical murine model For personal use only Control ‘Asthmatic’ mouse mouse 9
Slide 10: β2-adrenoceptor signaling pathways
β2-adrenoceptor signaling pathways For personal use only ligand The canonical cAMP-dependent New pathway discovered ~2000 pathway (Lefkowitz) Adenylyl cyclase βarrestin Activation of MAPKs cAMP-accumulation (ERK) 10
Slide 11: Effects of different beta-blockers on mucous in mouse asthma model
Effects of different beta-blockers on mucous in mouse asthma model For personal use only Alprenolol Carvedilol INV102 (nadolol) Proof of concept has been achieved in pre-clinical studies with inhaled INV102 11
Slide 12: Nadolol is different from other beta-blockers
Nadolol is different from other beta-blockers For personal use only 100 ERK1/2 activation Epinephrine 80 Beta arrestin signaling 60 Carvedilol Alprenolol 40 Propranolol 20 INV102 (nadolol) 0 -0.004 -0.003 -0.002 -0.001 0.001 0.501 1.001 Rate of cAMP accumulation 12
Slide 13: Alprenolol
Alprenolol For personal use only ligand β2 adrenoceptor cAMP-dependent βarr-dependent pathway pathway 13
Slide 14: Carvedilol
Carvedilol For personal use only ligand β2 adrenoceptor cAMP-dependent βarr-dependent pathway pathway 14
Slide 15: Carvedilol and alprenolol did not work
Carvedilol and alprenolol did not work For personal use only ligand β2 adrenoceptor cAMP-dependent βarr-ERK pathway pathway Asthma phenotype 15
Slide 16: Nadolol (acute)
Nadalol (acute) For personal use only ligand β2 adrenoceptor cAMP-dependent βarr-dependent pathway pathway 16
Slide 17: Nadolol (chronic)
Nadolol (chronic) For personal use only ligand β2 adrenoceptor ? cAMP-dependent βarr-dependent pathway pathway 17
Slide 18: Nadolol is different from other beta-blockers
Nadolol is different from other beta-blockers For personal use only 100 ERK1/2 activation Epinephrine 80 Beta arrestin signaling 60 Carvedilol Alprenolol 40 Propranolol 20 INV102 (nadolol) 0 -0.004 -0.003 -0.002 -0.001 0.001 0.501 1.001 Rate of cAMP accumulation 18
Slide 19: Conclusions
Conclusions The β2 adrenoceptor has two signaling pathways For personal use only > > 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 19
Slide 20: Mitchell Glass, M.D., Executive VP R&D and Chief Medical Officer
Mitchell Glass, M.D., Executive VP R&D and Chief Medical Officer For personal use only > 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) > Boa
Slide 21: INV102 (nadolol)
INV102 (nadolol) For personal use only > 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 NI
Slide 22: Medical, regulatory and commercial precedent
Medical, regulatory and commercial precedent For personal use only Precedent: Chronic Heart Failure (CHF) FROM TO CONTRAINDICATED STANDARD OF CARE Warning against use of After careful titration, beta blocker beta blockers in CHF for > 25 years. Carvedilol reduced mortality in Carvedilol annual sales
Slide 23: INV102: phase II trial design - mild asthma
INV102: phase II trial design - mild asthma For personal use only INCLUSION ORAL DOSING WITHDRAWAL ENDPOINTS 26wks 4wks Randomised Efficacy Controlled Randomize Nadolol Treatment Improved Clinical Trial Titration & Tolerability Placebo airway hyper- (N=30, 1:1 Placebo: Active) responsiveness Safety
Slide 24: INV102: phase II trial design - smoking cessation
INV102: phase II trial design - smoking cessation For personal use only INCLUSION ORAL DOSING WASHOUT ENDPOINTS 11-15wks 2wks Randomised Primary E (IWRS) 50% Decrease in # of O Nadolol Treatment (n=65) dose Controlled cigarettes per day P Clinical Trial 3wks titration & each during last 28 days II 5
Slide 25: INV102 (nadolol): oral program
INV102 (nadolol): oral program Airway inflammation 1H14 2H14 1H15 Next milestone For personal use only (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
Slide 26: Respiratory therapeutics: inhaled program
For personal use only Respiratory therapeutics: inhaled program INV102 (nadolol) in COPD & cystic fibrosis INV104 (zafirlukast) in asthma
Slide 27: Recent capital raise and development collaboration
Recent capital raise and development collaboration allow acceleration of clinical development For personal use only > Collaboration with 3M Drug Delivery systems > Inhalation development expertise > Proprietary formulation and device > Works will assess the feasibility of inhaled INV102 (nadolol) an
Slide 28: INV102 (nadolol): comparison oral vs inhaled
INV102 (nadolol): comparison oral vs inhaled Target Product Profile For personal use only 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 > Once daily dosing with no need for titration
Slide 29: INV102 (nadolol): inhaled program
INV102 (nadolol): inhaled program Airway inflammation 1H14 2H14 1H15 Next milestone For personal use only (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 fi
Slide 30: Invion: drugs in development
Invion: 3 drugs in development For personal use only > 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
Slide 31: Pipeline: 12-18 month outlook
Pipeline: 12-18 month outlook Airway inflammation 1H15 Next milestone For personal use only (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 E
Slide 32: Summary
For personal use only 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 exp
Slide 33: Dr Greg Collier, Managing Director and CEO
For personal use only 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