Targeted Therapeutics for Inflammatory Disease. Investor Presentation April 2014

Transcription

1 Targeted Therapeutics for Inflammatory Disease Investor Presentation April 2014

2 Forward Looking Statements / Safe Harbor This presentation and the accompanying oral commentary contain forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation and the accompanying oral commentary, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations, are forward looking statements. In some cases, you can identify forward-looking statements by terminology such as believe, will, may, estimate, continue, anticipate, intend, should, plan, might, approximately, expect, predict, could, potentially or the negative of these terms or other similar expressions. Forward looking statements appear in a number of places throughout this presentation and the accompanying oral commentary and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for AQX-1125 and our future product candidates, our intellectual property position, the degree of clinical utility of AQX-1125 and our future product candidates, particularly in specific patient populations, our ability to develop commercial functions, expectations regarding clinical trial data, our results of operations, cash needs, financial condition, liquidity, prospects, growth and strategies, the industry in which we operate and the trends that may affect the industry or us. Forward-looking statements involve known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our management s beliefs and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. 2

3 Corporate Highlights Small molecules against novel target (SHIP1) with broad anti-inflammatory potential AQX-1125: large, underserved markets - currently in Phase 2 trials for COPD and BPS/IC Positive results from two POC clinical trials Large, diverse library of next generation compounds Decisive near-term milestones - top-line Phase 2 clinical data expected in Q & Q Successful IPO > 2 yrs cash 3

4 Experienced Management David Main, President & CEO INEX Pharmaceuticals, QLT Stephen Shrewsbury, CMO Sarepta, MAP, Chiron, Glaxo Kamran Alam, CFO Angiotech, AnorMED, PwC Lloyd Mackenzie, VP Technical Ops QLT, Inflazyme 4

5 SHIP1 is an Attractive Drug Target SHIP1 is nature s way to regulate PI3K in immune cells PI3K All cells PI-4,5-P 2 PIP 3 SHIP1 Immune cells PI-3,4-P 2 PTEN All cells SHIP1 Activators Cancer Cell growth and survival Inflammation Cell activation and function SHIP1 activators have the potential to become the next generation of anti-inflammatory drugs 5

6 Roadmap for Clinical Indications Mucosal surfaces such as Airway, GI, Bladder A B +/+ -/- -/- +/+ -/- C Increased GM progenitors Infiltration of lungs with macrophages/neutrophils Airway remodeling/fibrosis KO mouse is viable & fertile, ~40% survival by 14 weeks Mixed inflammatory infiltrates Granuloma Fibrosis Colitis phenotype 6

7 Positive In Vivo Data for AQX-1125 Clinical Indica*on Animal Model Primary Endpoint COPD / Respiratory LPS Airway Inflamma/on (Rat) Reduc/on of neutrophils BPS / IC Ovalbumin Airway Inflamma/on (Rat) Smoke Airway Inflamma/on (Mouse) Bleomycin Fibrosis (Mouse) Cyclophosphamide Bladder Cys//s (Rat) Carrageenan Paw Edema (Mouse) Reduc/on of eosinophils Reduc/on of neutrophils Reduc/on of fibrosis Increase in survival Reduc/on of inflammatory pain Reduc/on of hemorrhage Reduc/on of edema IBD TNBS IBD (Rat) Reduc/on of adhesions / strictures Reduc/on of inflamma/on AQX-1125 not active in models of RA, MS, nor Uveitis Broad anti-inflammatory and anti-fibrotic activity consistent with SHIP1 KO mouse phenotype 7

8 Development Strategy / Opportunities Mucosal Inflamma*on Unmet Need Short Dura*on Trials Acute Endpoints Exacerba*ons, Flares, Pain Expand into Chronic Endpoints Lung/Airway COPD: Moderate-severe Chronic Rhinosinusitis Asthma: Steroid unresponsive, Moderate-severe Non-CF Bronchiectasis Churg-Strauss Syndrome Idiopathic Pulmonary Fibrosis Urinary Tract Bladder Pain Syndrome / Interstitial Cystitis (BPS/IC) Glomerulonephritis GI Eosinophilic Esophagitis Crohn's Disease Ulcerative Colitis Current Phase 2 trials: COPD and BPS/IC supported by preclinical and clinical POC 8

9 Clinical Development in Large, Underserved Markets Research/Preclinical Phase 1 Phase 2 AQX-1125 SHIP1 Activator Completed Ongoing SAD / MAD / FE Chronic Obstructive Pulmonary Disease (COPD) POC Asthma POC Chronic Obstructive Pulmonary Disease (COPD) Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) Other Respiratory, Urology, Gastrointestinal Phase 2-ready Next Gen SHIP1 Activator Future Inflammation Oncology Differentiated oral once daily product for multiple indications 9

10 AQX-1125 Clinical Program 10

11 AQX-1125 Overview Desirable drug properties suitable for oral once daily dosing One phase 1 and two positive POC clinical trials; > 100 subjects dosed Novel mechanism of action with broad antiinflammatory properties and strong translation from preclinical to clinical Issued patents in major markets; coverage until 2028 Aquinox currently holds worldwide rights 11

12 Phase 1: SAD PK Concentration (ng/ml) mg 400 mg 200 mg 100 mg 50 mg 17 mg t 1/2 =~21 h Time (h) AQX-1125 exhibits desirable PK suitable for oral once daily dosing 12

13 Phase 1: MAD PK Trough Conc (ng/ml) Time (h) Steady State 542 mg 250 mg 100 mg t 1/2 =~21 h Preclinical target coverage Human exposure above preclinical target coverage 13

14 Proof-of-Concept Trial Selection Cost-effective Short duration Precedent trials to use as benchmarks Well-defined inflammatory challenge/endpoints Ability to demonstrate: translation of preclinical results biological effect of targeting SHIP1 in humans Opportunity to demonstrate first-in-class activity in humans 14

15 Proof-of-Concept Trials First evaluation of SHIP1 target in humans COPD POC LPS challenge; model of the inflammatory mechanisms seen in COPD Cross-over trial; 40 NH volunteers, QD x 7 (2 dose levels) Sputum neutrophils powered to p<0.1; other cell counts measured for trend analysis Asthma POC Allergen challenge; model of the inflammatory mechanisms seen in allergic response Cross-over trial; 22 mild asthmatics, QD x 7 Late Asthmatic Response (LAR) powered to p<0.05; sputum cell counts measured for trend analysis Two different inflammatory challenges representing models for multiple inflammatory diseases 15

16 COPD POC: Inhibition of Sputum Neutrophils AQX-1125 met primary endpoint in healthy volunteers CI ( ) CI ( ) Note: sputum processing error for 200 mg dose cohort prevented efficacy analysis Robust inhibition of inflammation in COPD model 16

17 COPD POC: Sputum Leukocyte Populations Effect on Leukocyte Population Active/Placebo Ratio Treatment ratio favors active treatment with all evaluable leukocyte cell types 17

18 Comparative LPS Challenge Data Drug Class % Neutrophil Inhibition AQX-1125 SHIP1 activator 62% Ph p38 MAP kinase Inhibitor 50% Roflumilast (Daxas, Daliresp) PDE4 inhibitor 39% Prednisolone / Fluticasone Corticosteroids No effect AQX-1125 compares favorably to other anti-inflammatory drugs for COPD 18

19 Asthma POC: Inhibition of LAR AQX-1125 met primary endpoint in 22 mild-moderate asthmatics Favours ac/ve Favours placebo 20% reduction LAR (AUC 4-10h ) p=0.027 Abs Eos Abs Neut Abs Mac % Eos % Neut % Mac Ac*ve/Placebo Ra*o Primary and secondary endpoints supportive of AQX-1125 in allergic disease 19

20 Current AQX-1125 Phase 2 Development 20

21 Chronic Obstructive Pulmonary Disease ~600 million patients affected globally Despite numerous approved therapies, a majority of moderate to severe patients still suffer exacerbations High unmet need for effective oral anti-inflammatories that reduce exacerbations and slow/prevent disease progression AQX-1125 s anti-inflammatory and anti-fibrotic properties and its tolerability may provide clear competitive differentiation 21

22 Exacerbations Cause Morbidity and Mortality AQX Unstable Bronchodilators Stable Hurst et al, AJRCCM, 2009, 79: Pioneering FLAGSHIP trial in frequent exacerbators 22

23 FLAGSHIP Trial: Summary Objective: Evaluate AQX-1125 in COPD patients post exacerbation ~400 moderate to severe COPD patients from ~40 European sites Endpoints: Primary: Sized to detect effect of AQX-1125 (200 mg capsule once daily) vs placebo on recurrent COPD exacerbations over 12 weeks (reduction of Area Above the Curve for EXACT*) utilizing ediaries Secondary: CAT, PFT, safety, PK, healthcare utilization (rescue meds / hospitalization) Key Milestone Dates: First Pa/ent Q Top- line data Q Full data 2015 at Scien/fic Mee/ng *EXACT= EXAcerba/ons of Chronic obstruc/ve pulmonary disease Tool 23

24 EXACT-PRO Developed by Evidera Designed to standardize the method for evaluating the frequency, severity, and duration of acute exacerbations of COPD Patient reported outcome (PRO) daily questionnaire utilizing ediaries Developed with considerable regulatory consultation (FDA and EMA) FDA guidance received January 2014 Funded by consortium of pharma: AZ, Almirall, Bayer, BI, Forest, GSK, Merck, Novartis, Ortho-McNeil, Pfizer, Sepracor EXACT together with PFTs more robust evaluation of diseasemodifying drugs in unstable COPD patients 24

25 Bladder Pain Syndrome / Interstitial Cystitis Disease driven by chronic inflammation and pain following damage to bladder lining ~14 million affected in the US Common treatment approach: direct instillation for short-term relief of symptoms AQX-1125 preclinical results demonstrate decreased bladder hemorrhage and inflammatory pain After oral dosing, AQX-1125 reaches bladder via bloodstream and elimination in urine AQX-1125 s distribution and anti-inflammatory properties make it compelling for BPS/IC investigation 25

26 LEADERSHIP Trial: Summary Objective: Evaluate AQX-1125 in subjects with BPS/IC pain ~70 moderate to severe patients from ~20 Canadian sites Endpoints: Primary: Sized to detect effect of AQX-1125 (200 mg capsule once daily) vs placebo on reduction of mean pain score (11 point NRS*) at 6 weeks vs baseline utilizing ediaries Secondary: urinary symptoms, safety, PK, QOL Key Milestone Dates: First Pa/ent Q Top- line data Q Full data 2015 at Scien/fic Mee/ng *NRS= Numerical Ra/ng Scale 26

27 Key Milestones COPD First patient: Q Top-line Data: Q Scientific Meeting: 2015 BPS/IC First patient: Q Top-line Data: Q Scientific Meeting: 2015 Additional Phase 2 Trials: 1 st Phase 2 Trial Initiated: Q nd Phase 2 Trial Initiated: Q Next Generation Compounds: Lead Selection: Q Near-term data, Phase 3-readiness, and expanded market opportunities 27

28 Targeted Therapeutics for Inflammatory Disease Corporate Presentation