Advancing the Treatment of Chronic Inflammatory Disease Q1 CONFERENCE CALL

Transcription

1 Advancing the Treatment of Chronic Inflammatory Disease Q1 CONFERENCE CALL April 18, 26

2 Phase III SIMPADICO Results Phase III ACCLAIM Review & Update VP25 Neuro-inflammatory Program Q1 CONFERENCE CALL April 18, 26

3 Forward-Looking Statements This presentation contains forward-looking statements that involve risks and uncertainties, which may cause actual results to differ materially from the statements made. For this purpose, any statements that are contained herein that are not statements of historical fact may be deemed to be forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of Without limiting the foregoing, the words "believes," "anticipates," "plans," "intends," "will," "should," "expects," "projects," and similar expressions are intended to identify forward-looking statements. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause actual results, future circumstances, or events to differ materially from those projected in the forward-looking statements. These risks include, but are not limited to, those associated with the success of research and development programs, the adequacy, timing, and results of our clinical trials, the regulatory approval process, competition, securing and maintaining corporate alliances, market acceptance of the Company's products, the availability of government and insurance reimbursements for the Company s products, the strength of intellectual property, financing capability, the potential dilutive effects of any financing, reliance on subcontractors and key personnel and other risks detailed from time-to-time in the Company's public disclosure documents or other filings with the Canadian and U.S. securities commissions or other securities regulatory bodies. The forward-looking statements are made as of the date hereof, and the Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Numerical values indicating the statistical significance ("pvalues") of results included in this presentation are based on analyses that do not account for endpoint multiplicity, and therefore are for information only and are not intended to be used for any future regulatory submissions or in any future product labeling in jurisdictions where such uses are prohibited.

4 Peripheral Arterial Disease Market Overview and Unmet Needs Affects ~ 9 million in U.S. (12 million in Europe) Chronic inflammation is an underlying pathology PAD patients have 6-fold increased risk for heart attack and stroke 3% all-cause mortality within 5 years Over 16, at risk for progression to limb ischemia ~ 8, amputations per annum Estimated $5-$1 billion in costs resulting from surgical interventions

5 Double-blind, placebo-controlled, pivotal phase III trial 553 moderate-to-severe PAD patients at 5 centers Primary endpoint: Change in maximal walking distance Additional pre-specified endpoints: PAD- and CV-related events Quality of life Blood flow measures (ABI) hs-crp

6 Baseline Medication Placebo (n=273) Celacade (n=262) ACE-I / ARB 65% 61% Beta-blocker 46% 42% Other anti-hypertensives 54% 63% Anti-platelets 79% 74% Anti-hyperlipidemic 73% 73%

7 Results presented March 12th

8 Progression to CLI 1 Survival Distribution Function (%) Modified intent-to-treat Time to First Event (days) Celacade P=.3 Placebo

9 Ankle-Brachial Index Blood Vessel Function Placebo Ankle-Brachial Index Mean Change From Baseline Celacade p=.4 Week 6 Week 26 Per protocol

10 Health-related Quality of Life Change from Baseline - Week 26 Placebo Celacade p= p= p= Physical functioning Social functioning Mental health Per protocol, LOCF; SF-36 v2

11 Walking Impairment Questionnaire Change from Baseline - Week 26 Placebo Celacade 6 5 p= p= Speed Distance Per protocol, LOCF

12 High-Sensitivity CRP Change from Baseline (mg/l) Placebo Celacade 1..5 P =.9 P = Week 26 End of Study Change vs. placebo approx. 3% Modified intent-to-treatto-treattreat

13 C-Reactive Protein (CRP) CVD, including first and recurrent coronary events and stroke Type 2 diabetes mellitus Vascular events after stroke Dementia Hypertension hs-crp Myocardial infarction or angina in patients with PAD Poor outcome in acute coronary syndromes Sudden cardiac death Chronic heart failure Restenosis after coronary angioplasty

14 Risk Factors for Future Cardiovascular Events: WHS Lipoprotein(a) Homocysteine IL-6 TC LDLC slcam-1 SAA Apo B TC: HDLC hs-crp hs-crp + TC: HDLC Ridker PM et al, N Engl J Med 2;342: Relative Risk of Future Cardiovascular Events

15 hs-crp Adds Prognostic Information Beyond the Framingham Risk Score in All Major Cohorts Evaluated Framingham Adjusted Relative Risk 2 1 <1 1-3 >3 2 PHS 1 24 NHS 2 1 WHS <1 1-3 > HPFS MONICA <1 1-3 > CHS ARIC <1 1-3 > EPIC-Norfolk Reykjavik <1 1-3 >3 <1 1-3 >3 <1 1-3 >3 <1 1-3 >3 <1 1-3 >3

16 Clinical Predictive Value of Very Low as well as Very High Levels of hs-crp 8 Relative Risk of Future CV Events < >2 low risk Ridker PM, Cook N. Circulation 24;19: moderate risk hs-crp (mg/l) high risk

17 CRP Reduction for Statins and Celacade 5 Placebo Statin Placebo Celacade % Change in Median hs-crp CARE Pravastatin 5 years N = 472 PRINCE Pravastatin 12/24 weeks N = 2884 AFCAPS Lovastatin 1 year N = 5719 Bayer Cerivastatin 8 weeks N = 785 SSSS Simvastatin 4 months N = 249 SIMPADICO Celacade 1 year N = % on statins

18 High Sensitivity CRP Levels Patient Distribution by Cardiovascular Risk Category 5% 45% Percentage of Patients 4% 3% 2% 1% < > 3. low risk Modified intent-to to-treattreat moderate risk hs-crp (mg/l) high risk

19 Change in hs-crp Levels Patients with High hs-crp levels at Baseline (n=231; 65% on Statins) Mean Change From Baseline (mg/l) p =.4 p =.9 Placebo Celacade -3. Week 26 End of Study Modified intent-to to-treat; treat; 3<hs-CRP<5 mg/l at baseline

20 Change in hs-crp Levels Patients with High hs-crp levels at Baseline (1% on Statins; n=149) Mean Change From Baseline (mg/l) p =.26 p =.37 Placebo Celacade -3. Week 26 End of Study Modified intent-to to-treat; treat; 3<hs-CRP<5 mg/l at baseline

21 SUMMARY

22 Chronic Heart Failure Market Overview and Unmet Needs y Affects 4.7 million in the U.S. (5.1 million in Europe) y Chronic inflammation is an underlying pathology y Progressive, irreversible, results in death y Leading cause of hospitalization in elderly y Implicated in ~ 3, deaths each year y 5-year survival: 5% for all HF patients y $25 billion spent annually y Hospitalizations major cost driver

23 y Double-blind, placebo-controlled, pivotal phase III trial y 71 events, 2,4 patients / 176 centers (fully enrolled) y Advanced heart failure patients receiving current standard of care hospitalization or IV therapy for HF < 12 months; LVEF < 3% y Primary endpoint: composite of mortality or first cardiovascular hospitalization Dr. James Young Chairman, Division of Medicine Dr. Guillermo Torre-Amione Medical Director, Heart Transplant Program Dr. Jean-Lucien Rouleau Dean, Faculty of Medicine

24 Steering Committee James Young, Cleveland Clinic (Chairman) Stefan Anker, University of Berlin Robert Bourge, University of Alabama Wilson Colucci, Boston University Barry Greenberg, UCSD Medical Center Per Hildebrandt, University of Copenhagen Andre Keren, Bikur Holim Hospital Michael Motro, Sheba Medical Center Jan-Erik Otterstad, Central Hospital of Vestfold Craig Pratt, The Methodist Hospital (Houston) Jean Rouleau, University of Montreal François Sestier, University of Montreal Guillermo Torre-Amione, Texas Heart Institute Bernhard Winkelmann, University of Heidelberg

25 Baseline Patient Characteristics Phase II Age (years) /32 8/2 Ischemic heart disease % Ejection fraction, mean % /72 118/7 Gender (male/female) % Blood pressure

26 Chronic HF Phase II Results Kaplan-Meier Analysis of Major Events 1 Patients Free of Event (%) % in risk p=.5 Hazard Ratio =.371 Celacade Placebo Days

27 Chronic HF Phase II Trial Key Findings Significant reduction in deaths and hospitalizations Effects observed on top of standard drugs

28 hs-crp & Heart Failure 1. Composite of Death and Hospitalization.9 Event Free Survival p-value (log-rank): <.1 < < <7.32 >7.32 _ hs-crp Time Since Randomization (months) Circulation, Anand et al. C-Reactive Protein in Heart Failure, September 25

29 We know there is a strong correlation between elevated high-sensitivity C-reactive protein levels and increased mortality and morbidity in heart failure patients. I am therefore very encouraged by the recent finding that Celacade significantly reduced elevated hs-crp levels in patients with cardiovascular disease, as I believe this bodes well for the primary endpoint of ACCLAIM. Guillermo Torre-Amione MD, PhD, FACC Medical Director, Heart Transplant Program Methodist DeBakey Heart Center at The Methodist Hospital US Principal Investigator, ACCLAIM Study

30 Enrollment Enrollment Enrollment Enrollment Completed Initiated Completed Initiated Q3 Q3 Event Event Target Target Reached Reached Final Final Assessments Assessments Completed Completed *Forward-looking *Forward-looking statement statement Results Results Expected* Expected* May May Database Database Lock Lock Expected* Expected* Nov Nov Jan Jan Apr Apr H1 H1 6 6

31 NEURO-INFLAMMATORY DISEASE PROGRAM

32 VP25 Lead candidate from a new class of drugs Targeting neuro-inflammatory disorders Phase I development successfully completed Preparing to initiate phase II development Influences inflammation across blood-brain barrier

33 Advancing the Treatment of Chronic Inflammatory Disease Q1 CONFERENCE CALL April 17, 26