Announcement PDF Invion Limited (ASX:IVX) Clinical-stage life sciences company targeting chronic inflammation Corporate Presentation April | 2014 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 > 3 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 Management team with proven track record Invion’s management and board have significant experience repurposing drugs for new markets and guiding drugs through FDA regulatory and approval processes. Greg Collier, PhD., Managing Director and Chief Executive Officer > 20 year career in pharmaceutical 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., Executive VP R&D and Chief Medical Officer 4 > 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) Recent capital raise and development collaboration allow acceleration of clinical development 5 > Collaboration with 3M Drug Delivery systems > Inhalation development expertise > 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 > Completion of $5M placement to institutional and professional investors, announcement of $2M Rights Issue Targeting respiratory disease INV102 (nadolol) - beta adrenergic inverse agonist INV104 (zafirlukast) - leukotriene receptor antagonist Spectrum of airway disease and opportunities Global market size: $34B Exercise Induced Asthma 7 Mild Asthma Moderate Asthma Severe Asthma Chronic Bronchitis $2.4B $1.2B Smoker’s cough Cystic Fibrosis Zafirlukast Nadolol Monotherapy + combinations Monotherapy + combinations INV102 (nadolol) > 8 Nadolol is uniquely an inverse -agonist in the airway > inactivates intracellular inflammatory events that are stimulated spontaneously or by  agonists > Hypothesized to utilize the beta-arrestin pathway > 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 Severe airway diseases share the phenotype Severe asthma COPD Cystic fibrosis 9 Preclinical studies demonstrate airway healing Control lung tissue Lung tissue of ‘asthmatic’ mice: epithelial cells have been converted to mucusproducing goblet cells. No effect of alprenolol. Lung tissue of ‘asthmatic’ mice treated with INV102 (nadolol) for 28 days: restored epithelium Proof of concept has been achieved in pre-clinical studies with inhaled INV102 10 Medical, regulatory and commercial precedent Precedent: Chronic Heart Failure (CHF) FROM TO 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) Invion target: Chronic Obstructive Pulmonary Disease (COPD) 11 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 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) INV102: phase II trial design - mild asthma Randomised Controlled Clinical Trial Randomize INCLUSION ORAL DOSING WITHDRAWAL 26wks 4wks ENDPOINTS Efficacy Nadolol Treatment Titration & Tolerability (N=30, 1:1 Placebo: Active) Improved Placebo airway hyperresponsiveness N=60 Mild persistent asthma Randomize Safety Titration and Bronchoscopy Substudy (n=30, 1:1 Placebo: Active) NIH Sponsored Placebo tolerated over 6 mo dosing NCT:01804218 PI & Protocol Chair: Nicola Hanania, MD Active clinical trial sites include: 12 bronchoscopy INV102: phase II trial design - smoking cessation INCLUSION ORAL DOSING WASHOUT 11-15wks 2wks Primary Randomised (IWRS) Controlled Clinical Trial ENDPOINTS Nadolol Treatment (n=65) 3wks titration & 5-8wks maintenance 50% dose each week Decrease in # of cigarettes per day during last 28 days Safety N=130 Failed to quit + COPD and chronic cough Placebo Control (n=65) “titration” & maintenance Placebo Change in FEV1, exacerbations, adverse events NCT:01825122 PI: Mario Castro, MD Active clinical trial sites include: 13 Birmingham, Alabama E O P II M E E T I N G INV102 (nadolol): oral program Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) 14 INV102 (nadolol) = beta adrenergic inverse agonist Asthma oral program, ongoing phase II study Smoking cessation oral program, phase II interim and final data and EOP2 Completion 2Q15 commence ph III EOP2 4Q14 Respiratory therapeutics: inhaled program INV102 (nadolol) in COPD & cystic fibrosis INV104 (zafirlukast) in asthma 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 > 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 > New indication limited to smoking cessation systemic side effects > Target long term regular use for chronic airway diseases > 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 LABA + ICS (Asthma), antibiotics (CF), and LAMA (CF) + 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 16 > Safety and efficacy data in combination with INV102 (nadolol): inhaled program Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic inverse agonist Asthma oral program, ongoing phase II study Smoking cessation oral program, phase II interim and final data and EOP2 commence ph III COPD inhaled monotherapy: formulation and development pre-IND, commence ph I Asthma Cystic fibrosis 17 Completion 2Q15 feasibility: inhaled monotherapy + ICS feasibility: inhaled monotherapy + antibiotic EOP2 4Q14 Pre IND 1Q15 INV104 (zafirlukast) > Nanomolar potent Leukotriene Receptor Antagonist (LTRA) or anti-leukotriene > Targeted as first inhaled non-steroidal anti-inflammatory treatment for asthma > Large market potential with mitigated risk of a reformulated drug > Accolate® (zafirlukast) > Developed by ICI / AstraZeneca, program headed by Dr. Glass > First LTRA to be approved by FDA, used worldwide as oral tablet for asthma > Well established clinical & safety profile > Non-oral uses never actively pursued by AZ, despite well established activity by inhalation route > Invion / 3M collaboration accelerates inhaled drug franchise, target = asthma > Data to date > 18 > Well defined CMC/TOX/ADME and safety profile: > 4M patients as oral Accolate (AZ) > 7 studies showed excellent prevention of asthma, cold air and exercise induced bronchospasm (EIB) without detectable drug blood levels Intellectual Property position > Expired zafirlukast patents (public domain) > New patent protection from combination, delivery, and linked diagnostic filings INV104 (zafirlukast): comparison oral vs inhaled Target Product Profile Oral (Accolate®) Label Inhaled INV104 (zafirlukast) > Astra Zeneca patent for zafirlukast expired > IP protection based on 3M formulation and device > Twice per day dosing with food effect, suicidal > Once (or twice) daily dosing with no systemic side ideation warning, and liver toxicity reported > Limited commercial uptake as a generic drug > Not indicated for PRN (as needed) use effects > Novel monotherapy with opportunities for combinations > Approved for single dose prophylaxis of Exercise-Induced Bronchospasm (EIB) > Not indicated for reducing Long Acting Beta Agonist (LABA) children > Not indicated for reducing use of corticosteroids > Indicated for reducing use of corticosteroids > No indication or clinical experience in children > Indicated for use in children 5 years of age or under 12 years of age 19 > Indicated to reduce use of LABA in adults and above with mild asthma or EIB INV104 (zafirlukast): inhaled program Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic inverse agonist Asthma oral program, ongoing phase II study Smoking cessation oral program, phase II interim and final data and EOP2 commence ph III COPD inhaled monotherapy: formulation and development pre-IND, commence ph I Cystic fibrosis 20 2Q15 EOP2 4Q14 Pre IND 1Q15 feasibility: inhaled monotherapy + ICS feasibility: inhaled monotherapy + antibiotic Asthma INV104 (zafirlukast) = leukotriene receptor antagonist Asthma inhaled monotherapy: formulation and development Asthma Completion IND, commence ph I feasibility: inhaled combination therapies IND 2Q15 Targeting inflammatory disease INV103 (ala-Cpn10): modified natural human protein INV103: Mechanism of action HSP10 22 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. (Reproduced from Shields A.M., et. al., 2011, Clin and Exp. Immunology, 165, 292-300) INV103 (ala-Cpn10): background and rationale > > > > Minimally modified form of naturally occurring protein Maintains heptameric structure and function Intracellular function: prevent protein misfolding Extracellular function: Cpn10 proposed as a founding member of the Resolution Associated Molecular Pattern (RAMPs) family (Shields et al, Clin Exp Immunol, 2011, 165: 292-300) a critical component of prevention of autoimmunity > Significant clinical data base > 250 patients > demonstrated anti-inflammatory and immunoregulatory activity in multiple indications including RA, psoriasis > Strong pre-clinical data in lupus animal model (3 studies) > 23 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) > Toxicology support through 3 months’ dosing > Intellectual Property position: composition of matter protection in all major markets (US 2026) INV103: completed clinical trials 24 Phase Indication Route Total patients INV103 patients Doses 1a Healthy volunteers IV/SC 19 14 1.2, 5.5, 10mg IV 5mg SC 1b Multiple Sclerosis IV 12 9 2.5 or 5mg, 5 doses 2a Multiple Sclerosis IV 50 39 Placebo, 5mg 2 Ulcerative Colitis IV 8 8 5mg 2x weekly 2a Plaque Psoriasis IV 24 24 5, 7.5 or 10mg 2x weekly 2a Rheumatoid Arthritis IV 23 23 5, 7.5 or 10mg 2x weekly 1a Healthy volunteers SC 24 16 10,30,60,100mg sc 1a Healthy volunteers SC 22 17 30, 30x2, 60, 60x2, 80mg/weekly 2a Rheumatoid Arthritis SC 155 105 Placebo, 25mg, 75mg 2x weekly INV103 (ala-Cpn10): autoimmune program Airway inflammation 1H14 2H14 1H15 Next milestone (calendar year) INV102 (nadolol) = beta adrenergic inverse agonist Asthma oral program, ongoing phase II study Smoking cessation oral program, phase II interim and final data and EOP2 commence ph III COPD inhaled monotherapy: formulation and development pre-IND, commence ph I Completion 2Q15 EOP2 4Q14 Pre IND 1Q15 feasibility: inhaled monotherapy + ICS feasibility: inhaled monotherapy + antibiotic Asthma Cystic fibrosis INV104 (zafirlukast) = leukotriene receptor antagonist Asthma inhaled monotherapy: formulation and development IND, commence ph I IND 2Q15 feasibility: inhaled combination therapies Asthma Autoimmune disease 25 INV103 (ala-Cpn10) = modified natural human protein Lupus (SLE) completion ph II study, IV/SC bridging study Partner INV103: phase II trial design - lupus INCLUSION 1 month, twice-weekly dosing of INV103 (ala-Cpn10) or placebo Double-blind Randomised Controlled Cohort 1 10mg i.v. Complete analysis of safety, pharmacokinetics, biomarkers Data provided under confidentiality to potential partners Data supported on Trupoints® (“Analysis”) Cohort 2 30mg i.v. Analysis N=32 Cohort 3 100mg i.v. 8 per cohort 6 active 2 placebo Mild lupus without kidney disease NCT:01838694 26 Analysis Cohort 4 300mg i.v. Co-PIs: Stanley Cohen, MD Alan Kivitz, MD Active clinical trial sites include: Analysis Pipeline: 12-18 month outlook Airway inflammation INV102 (nadolol) = beta adrenergic inverse agonist Asthma oral program, ongoing phase II study phase II trial complete Smoking cessation oral program, phase II interim and final data and EOP2 phase III commenced COPD inhaled monotherapy: formulation and development phase I commenced Completion 2Q15 EOP2 4Q14 Pre IND 1Q15 feasibility: inhaled monotherapy feasibility: inhaled monotherapy Asthma Cystic fibrosis INV104 (zafirlukast) = leukotriene receptor antagonist Asthma inhaled monotherapy: formulation and development IND, phase I commenced IND 2Q15 feasibility: inhaled combination therapy Asthma Autoimmune disease 27 INV103 (ala-Cpn10) = modified natural human protein Lupus (SLE) completion ph II study, IV/SC bridging study Partner Partner 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 Corporate snapshot 29 Sector Life Sciences (Biotechnology) Principal activities Clinical-stage pharmaceutical drug development Pipeline 3 drug assets, multiple clinical and pre-clinical programs Operations Australia & USA ASX code IVX Share price (3-Apr-14) $0.075 (7.5 cents) Shares on issue ~540M Options on issue ~45M Market cap (3-Apr-14) $40.5M Cash at bank (31-Dec-13) $1.9M Placement completed (21-Feb-14) $5.0M Rights Issue completed (28-Mar-14) $0.9M 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 Corporate Presentation April | 2014