Announcement PDF Invion Limited (ASX:IVX) Clinical-stage life sciences company targeting chronic inflammation Corporate Presentation February | 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 > 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 > Collaboration with 3M Drug Delivery systems > Inhalation development expertise > Proprietary formulation and device > Collaboration 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 5 Invion pipeline focuses on enhanced shareholder value Airway Inflammation Non-clinical INV102 (nadolol) = beta adrenergic inverse agonist Oral: Asthma Nadolol in Mild Asthma (NIMA) clintrials.gov Oral: Smoking Cessation COPD subjects: clintrials.gov IND Phase I Phase II = leukotriene receptor antagonist IND 1H2015 Inhaled: Autoimmune Disease Non-clinical INV103 (ala-cpn-10) = modified natural human protein 6 IND Phase I Phase II Next Milestone Payment / License IV: Lupus / RA Completed (calendar year) Completion 1H 2015 EOPII 4Q 2014 Pre IND 1Q 2015 Inhaled: INV104 (zafirlukast) Next Milestone Planned 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 Mild Asthma Moderate Asthma Severe Asthma Chronic Bronchitis $2.4B $1.2B Smoker’s cough Cystic Fibrosis Zafirlukast: Monotherapy + combinations Nadolol: Monotherapy + combinations 8 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 > 9 > 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 INV102 (nadolol) > 10 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 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 11 Severe airway diseases share the phenotype Severe Asthma COPD Cystic Fibrosis 12 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) 13 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 14 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 Commenced 2013 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 Expected completion 2015 INV102: phase II trial design – smoking cessation 15 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 Commenced 2013 Inclusion criteria Previously failed to quit, have COPD and chronic cough Principal Investigator Prof Mario Castro Sites Washington University (St Louis) Doses 2.5mg, 5mg, 10mg, 25mg, 50mg (dose titration) Primary endpoints Change from baseline in number of cigarettes smoked per day for the last 28 days on study medication Secondary endpoints Number of cigarette-free days; Saint George’s Respiratory Questionnaire; markers of COPD including sputum 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 Expected Completion H2 2014 Respiratory therapeutics: inhaled program INV102 (nadolol) in COPD & cystic fibrosis INV104 (zafirlukast) in asthma INV102 (nadolol): comparison oral vs inhaled Target Product Profile Oral 17 Inhaled IP protection based on titration and method of use (USA) IP protection based on 3M formulation and device Once daily dosing including titration to avoid systemic side effects Invion phase II and III data limited to 13 weeks for smoking cessation New indication limited to smoking cessation Once daily dosing with no need for titration and no 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 (CF) Safety and efficacy data in combination with LABA + ICS (Asthma), antibiotics (CF), and LAMA + ICS (COPD) Limited data on reducing cough, sputum production, “smoker’s cough”, avoiding use of steroids or preventing/ameliorating exacerbations Indicated for reducing cough, sputum production, “smokers’ cough”, decreasing use of steroids or preventing/ameliorating exacerbations No indication or clinical experience in children under 12 years of age Indicated for use in children 5 years of age or above with severe asthma or CF INV104 (zafirlukast): comparison oral vs inhaled Target Product Profile Oral (Accolate®) Label 18 Inhaled (INV104) Astra Zeneca patent for zafirlukast expired IP protection based on 3M formulation and device Twice per day dosing with food effect, suicidal ideation warning, and liver toxicity reported. Once (or twice) daily dosing with no systemic side effects Limited commercial uptake as a generic drug Novel monotherapy with opportunities for combinations Not indicated for PRN (as needed) use Approved for single dose prophylaxis of Exercise-Induced Bronchospasm (EIB) Not indicated for reducing Long Acting Beta Agonist (LABA) Indicated to reduce use of LABA in adults and children Not indicated for reducing the use of corticosteroids Indicated for reducing use of corticosteroids No indication or clinical experience in children under 12 years of age Indicated for use in children 5 years of age or above with mild asthma or EIB Respiratory pipeline: based on stage of development Pre-IND Phase I Phase II Phase III INV102 (nadolol) NIH funding: moderatesevere asthma Asthma oral Mild disease: NIH funded Chronic bronchitis: oral Smoking cessation in patients with pre-existing COPD COPD: inhaled monotherapy Asthma inhaled Monotherapy +ICS Cystic fibrosis inhaled Monotherapy +antibiotic IND EOPII Phases I and II IND Phases I and II IND Phases I and II: EU IND Phases I and II INV104 (zafirlukast): inhaled Asthma monotherapy Asthma combinations Current Activities 19 IND Phases I and II Future Activities Smoking cessation Targeting inflammatory disease INV103 (ala-Cpn10): modified natural human protein INV103: Mechanism of action HSP10 21 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) > 22 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 23 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: phase II trial design – lupus 24 Trial name INV103 (ala-Cpn10) in mildly active Systemic Lupus Erythematosus (lupus) Trial design Double-blinded, randomized, placebo-controlled, intravenous dosing Patients 32 subjects (8 subjects per dose cohort, 4 cohorts) Timing Commenced Q3 2013 Inclusion criteria Mild lupus without clinical kidney disease Principal Investigator Alan Kivitz, M.D., Stanley Cohen, M.D. 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 Regulatory Status www.clinicaltrials.gov ID: NCT01838694 Completion 2014 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 26 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 (21-Feb-14) $0.089 (8.9 cents) Shares on issue ~530M Options on issue ~30M Market cap (21-Feb-14) $47M Cash at bank (31-Dec-13) $1.864M Placement completed (21-Feb-14) $5M Rights Issue announced (21-Feb-14) $2M 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 February | 2014