Announcement PDF INV104 (zafirlukast) Target: a novel inhaled non-steroidal anti-inflammatory treatment for asthma Target: an inhaled reformulation of a successful oral therapeutic for asthma INV104 (zafirlukast): > Leukotriene-receptor antagonist (LTRA) or “anti-leukotriene” that reduces inflammation, constriction of the airways, and the build-up of mucus in the lungs > Approved worldwide as an oral tablet for asthma (AstraZeneca) > Well established clinical efficacy & safety profile > Inhaled proof of concept using propellants that are now banned (CFCs) > Inhaled formulation indicated as monotherapy for mild persistent asthma and exercise-induced asthma > 2 Indicated to reduce inhaled corticosteroid (ICS) dependency in adults and children > as an alternative as first controller medication in mild persistent and moderate asthma > by addition to low dose ICS treatment rather than doubling ICS > by enabling reduced ICS dose “steroid sparing” in steroid-dependent asthma Inhaled zafirlukast an anti-leukotriene: background and rationale Defined safety profile Defined CMC Airway & nasal secretions are rich in LTC4, D4 and E4 (cysteinyl leukotrienes) Strong scientific rationale 3 Excellent flow characteristics shown in DPI (Turbuhaler) as well as conventional pMDI (1980s-90s) Full toxicology package completed using CFC-based delivery system Single and multiple inhaled forms showed no dose-limiting side effects or blood levels Known tox/ ADME profile > Zeneca (now A/Z) stopped inhaled development in mid 1990s. > Zafirlukast and montelukast have resisted formulation in non-cfc propellant systems. 200mcg demonstrated 12 hour protection from allergen. Once daily dosing achievable at <1000mcg/day Established efficacy & defined dose for inhalation FDA pre-IND established framework for reformulation of zafirlukast Agreement reached with FDA on: > > > 4 chemistry manufacturing and controls (GMP) > active pharmaceutical ingredient (API) with drug master file (DMF) > formulation: dry powder inhaler (DPI) approved for development toxicology and bioanalytical assay (GLP) to support 4 weeks’ dosing > 2 species for 28 days: naso-pulmonary exposure > 1 species for 6 months IND submission and clinical program > phase I: single rising dose study for safety (paradoxical bronchoconstriction) and pharmacokinetics > phase I: multiple dose safety study for safety (paradoxical bronchoconstriction) and pharmacokinetics > phase II: challenges to reprise previous studies: cold air, exercise and allergen [cat and ragweed]; steady state dosing for signs and symptoms of asthma [diary card] and attenuation of response to exercise and/or allergen Inhaled Product Rationale Oral Forms Risk of neuropsychiatric/suicide ideation events? Risk of liver toxicity ? Greater efficacy due to higher airway concentrations Potential for once a day dosing ? Potential for expanded EIB claims ? Rapid onset-of-action for prophylaxis ? Potential claim to reduce use of Steroids/ LABA ? Potential claim for use in children >5 years ? Combination with ICS for anti-inflammatory effect? 5 Singulair Prevention Only Inhaled Form Hovione CMC collaboration mitigates major risk of inhaled zafirlukast development Formulation & device partner, Hovione > Invion will collaborate with Hovione to develop the proprietary novel technology – a dry powder formulation of zafirlukast and the accompanying inhalational delivery device > under the terms of the agreement, Hovione will provide chemistry and manufacturing services to develop and optimise the dry powder inhalation formulation which will be delivered using its proprietary device technology known as the XCaps inhaler system > Hovione device is ideally suited for fixed combination with ICS, bronchodilators, or INV102 (nadolol). > IP protection provided under licence via Hovione formulation and device, Invion retains commercialisation rights CMC solution complements existing and planned toxicology and clinical packages > previously completed using CFC-based device > 6 Clinical proof of concept based on inhalational challenge studies; previously completed using CFC-based device About Hovione and the XCaps inhaler > International company with over 50 years’ experience in the development and compliant manufacture of active pharmaceutical ingredients and drug product intermediates > With four FDA inspected sites in the U.S., China, Ireland, and Portugal, the company focuses on the most demanding customers, in the most regulated markets > In the inhalation area, Hovione is the only independent company offering such a broad range of services. XCaps is a patent protected device filed and granted in over 40 countries, including US (US 8677992) and EU (EP 2546460). XCaps device is simple, reusable and lowcost. This DPI is indicated for applications where a chronic or a medium term acute capsule based delivery of an API is needed. 7 Expected placement of inhaled zafirlukast in treatment regimes > As many as 334 million people have asthma which occurs in people of all ages. Wheeze is the most common symptom and the burden of disability is high. > In 2007 the U.S. spent over $56 billion on asthma care, of which nearly $27 billion was spent on pediatric asthma. Inhaled zafirlukast 8 > targeted for use as a controller/ preventer with few or no side effects for the full range of asthma therapy > especially useful in LTD4-driven asthma including aspirin sensitivity and in children > indicated as steroid sparing > inhaler will facilitate substitution for inhaled corticosteroids (ICS) > for many patients, inhaled product alone (monotherapy) will be effective Inhaled zafirlukast program: progress and clinical development strategy Clinical benefits  FDA approved as an oral asthma therapy  Proof of concept previously conducted using inhaled drug  Non-steroidal  Higher local concentrations without systemic exposure (decreased risk of generic duplication) Status of collaboration with Hovione for proprietary formulation and device using Hovione’s patented XCaps inhaler system  Formulation and device selected  Program of works for manufacture of toxicology and clinical supplies > Formulation complete for toxicology (non GMP) (3Q2015) > Toxicology supplies manufactured (3Q2015) > Clinical supplies manufactured to support IND and Phase 1 (4Q2015-1Q2016) Development program  Pre-IND status with FDA  Formulation and device collaboration 9 > Commencement of toxicology studies (4Q2015) > IND submission (1Q2016) > Phase I and Phase II clinical studies in (Q1-4 2016) Disclaimer • The information in this presentation does not constitute personal investment advice. The presentation is not intended to be comprehensive or provide all information required by investors to make an informed decision on any investment in Invion Limited ACN 094 730 417 (Company). In preparing this presentation, the Company did not take into account the investment objectives, financial situation and particular needs of any particular investor. • Further advice should be obtained from a professional investment adviser before taking any action on any information dealt with in the presentation. Those acting upon any information without advice do so entirely at their own risk. • Whilst this presentation is based on information from sources which are considered reliable, no representation or warranty, express or implied, is made or given by or on behalf of the Company, any of its directors, or any other person about the accuracy, completeness or fairness of the information or opinions contained in this presentation. 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