Corporate Presentation. April 2017

Transcription

1 Corporate Presentation April 2017

2 Forward-Looking Statements Certain of the statements made in this presentation may constitute forward-looking information within the meaning of applicable Canadian securities law and forward-looking statements within the meaning of applicable U.S. securities law. These forward-looking statements or information include, but are not limited to statements or information with respect to the projected worth of the lupus nephritis (LN) market, that voclosporin is potentially a best-inclass calcineurin-inhibitor (CNI) with robust intellectual property exclusivity and the likelihood of data exclusivity in major markets, the expectation that voclosporin will be the only CNI with a label for LN, the expected progress of the AURION study; the anticipated commercial potential of voclosporin for the treatment of LN; and anticipated interactions with the US Food and Drug Administration. When used in these marketing materials, the words anticipate, will, believe, estimate, expect, intend, target, plan, goals, objectives, may and other similar words and expressions, identify forward-looking statements or information. We have made numerous assumptions about the forward-looking statements and information contained herein, including among other things, assumptions about: the market value for the LN program; that another company will not create a substantial competitive product for Aurinia s LN business without violating Aurinia s intellectual property rights; and the size of the LN market. Even though the management of Aurinia believes that the assumptions made and the expectations represented by such statements or information are reasonable, there can be no assurance that the forwardlooking information will prove to be accurate. Forward-looking information by their nature are based on assumptions and involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aurinia to be materially different from any future results, performance or achievements expressed or implied by such forward-looking information. Should one or more of these risks and uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in forward-looking statements or information. Such risks, uncertainties and other factors include, among others, the following: the market for the LN business may not be as estimated; and competitors may arise with similar products. Although we have attempted to identify factors that would cause actual actions, events or results to differ materially from those described in forwardlooking statements and information, there may be other factors that cause actual results, performances, achievements or events to not be as anticipated, estimated or intended. Also many of the factors are beyond our control. There can be no assurance that forward-looking statements or information will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Accordingly you should not place undue reliance on forward-looking statements or information. Except as required by law, Aurinia will not update forward-looking information. All forward-looking information contained in this presentation is qualified by this cautionary statement. Additional information related to Aurinia, including a detailed list of the risks and uncertainties affecting Aurinia and its business can be found in Aurinia s most recent Annual Information Form available by accessing the Canadian Securities Administrators System for Electronic Document Analysis and Retrieval (SEDAR) website at or the U.S. Securities and Exchange Commission s Electronic Document Gathering and Retrieval System (EDGAR) website at 2

3 Company Highlights Clinical-stage biopharmaceutical company focused on the global nephrology and autoimmunity markets Seasoned management team which led the development of Cellcept, the standard of care in the treatment of lupus nephritis (LN) Lead Program Voclosporin is entering Phase III for the treatment of LN a disease characterized by significant morbidity & mortality drug achieved highest complete remission rate of any global LN study [49.4% (p<.001) at 48 weeks] Large unmet medical need with readily available $1B+ market; extensive IP protection in the US as well as data exclusivity in major markets 3

4 SLE & LN Overview & Symptomatology CENTRAL NERVOUS SYSTEM Headaches, dizziness, memory disturbances, vision problems, seizures, stroke, or changes in behavior SLE is a chronic, complex and often disabling autoimmune disorder Affects over 500K people in the US (mostly women) 1 Highly heterogeneous, affecting range of organ & tissue systems 1 LUNGS Pleuritis, inflammation, or pneumonia HEART Chest pains, heart murmurs KIDNEYS Inflammation LN is an inflammation of the kidneys caused by SLE & represents a serious progression of SLE Up to 60% of SLE patients develop LN 2 Leakage of blood proteins into the urine (proteinuria) is clinical sign of LN 4 BLOOD Anemia, decreased white cells, increased risk of blood clots Widespread fatigue, fever, joint pain, muscle aches, photosensitivity, rashes, hair loss, oral ulcers, anxiety & depression Straightforward disease outcomes early response correlates w/long term outcomes; measured by proteinuria 2 Debilitating and costly, often leading to ESRD, dialysis, renal transplant, and death 2 Severe LN progresses to ESRD within 15 years of diagnosis in 10% to 30% of patients 3 1. Lupus Foundation of America website: 2. NIDDK, Lupus Nephritis. Accessed July 26, Maroz N, Segal MS. Am J Med Sci. 2013;346(4): Lupus Foundation of America, Accessed July 26, 2016.! NO FDA OR EMA APPROVED LN THERAPIES 4

5 The Severity of Lupus Nephritis SLE patients w/renal damage and ESRD have 14-fold and >60-fold increased risk, of premature death, respectively Standardized mortality ratio Mok et al, Arthritis Rheum

6 Cost Burden of Lupus Nephritis Average Annual Cost of Illness per Patient by Condition* $0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 Asthma Hypertension Diabetes COPD Bipolar Disorder Heart Disease Rheumatoid Arthritis Ulcerative Colites Crohns Disease SLE (no nephritis) Lupus Nephritis Medical Costs Absence Costs Short Term Disability * Carls G, et al. J Occup Environ Med. 2009;51:

7 % of Patients Proteinuria Correlates with Long-Term Outcomes Rapid control & reduction of proteinuria in lupus patients may show a reduction in the need for dialysis 1 120% LN patient survival without ESRD based on treatment response 1 100% 8% 80% 57% 60% 87% 40% 92% 20% 0% 43% 13% Complete Remission Partial Remission No Response Not on 10 years On Dialysis at 10 years 1. Chen YE, et al. Clin J Am Soc Nephrol. 2008;3(1): Response = 50% reduction in proteinuria; Remission = proteinuria <.33 g/24 hrs.. 7

8 % of Patients STANDARD THERAPY for PROLIFERATIVE LN Proliferative LN: Give IV Methylprednisolone 0.5-1g/d for 1-3 days followed by Oral Prednisone 1mg/kg/d ideal body weight, Maximum 80 mg/d, Taper Over Weeks PLUS: IV Cyclophosphamide 0.5-1g/m 2 Monthly for 6 months * Or PO Cyclophosphamide 1-1.5mg/kg/d, maximum 150 mg/d for 2-4 months 24 week Partial Response & Complete Remission Rates with Cyclophosphamide and MMF 2 60% 50% 40% 30% 20% 10% 0% 53% 56% 8% 9% Partial Response Complete Remission Cyclophosphamide MMF Or IV Cyclophosphamide 500 mg every 2 weeks for 3 months: LOW-DOSE- EURO-LUPUS REGIMEN Or Oral MMF 2-3g/d for 6 months Results of the Aspreva Lupus Management Study (ALMS) showed that the majority of patients failed to achieve CR at 24 weeks for both of these first-line therapeutics 2 A better solution is needed to improve renal response rates for LN 1. Hahn BH, et al. Arthritis Care Res (Hoboken). 2012;64(6): Appel GB, et al. J Am Soc Nephrol. 2009;20(5):

9 Recently Completed Clinical Trials in LN Drug Class Target Clinical Trial Status Abatacept-BMS CTLA4-Ig CTLA4-B7 Phase 3- FAILED Abatacept-ACCESS CTLA4-Ig CTLA4-B7 Phase 2- FAILED Laquinamod Small Molecule Inflammation Phase 2- ENCOURAGING Rituximab Monoclonal Antibody CD20 Phase 3- FAILED Ocrelizumab Monoclonal Antibody CD20 Phase 3 - STOPPED Sirukumab Monoclonal Antibody IL-6 Phase 2-FAILED Bortezomib Proteasome Inhibitor Plasma Cells Phase 4- STOPPED Anti-CD40 Ligand Monoclonal Antibody CD40 Ligand Phase 2- STOPPED Tabalumab Monoclonal Antibody BLyS Phase 3- FAILED Anti-TWEAK Monoclonal Antibody TWEAK Phase 2- FAILED Parikh et al JASN 2016

10 Mean total cholesterol Concentration (ng/ml) Our Solution - Voclosporin - Key Benefits 1,2,3 %CNI %CNI Cases of new onset diabetes (12 months) %CNI VCS CsA Time (h) Increased Potency vs. cyclosporine A, allowing lower dosing requirements 1 Limited inter & intra patient variability allowing flat dosing 1, Concentration (ng/ml) r = r = ,000 1,250 1,500 Concentration (ng/ml) Total Cholesterol (Study Isa05-25) Mean ±95% CI VCS CsA Drug therapy ends Less cholesterolemia than cyclosporine A 1 Voclosporin Limited incidence of glucose intolerance & diabetes at targeted doses vs. tacrolimus 2 25 r = Concentration (ng/ml) Low conc. Mid conc. Voclosporin Tacrolimus Week 1. Aurinia Data on file 2. Busque S, et al. Am J Transplant. 2011;11(12): & AURA LV Data 3. AURA-LV Data on file 10

11 Voclosporin LN Clinical Program Overview AURA-LV (Phase IIB) Study demonstrated that voclosporin added to SoC can increase the speed and rate of complete and partial remission in the presence of extremely low physiological steroids levels Statistically significant higher CR, PR, time to CR/PR, UPCR reduction & SLEDAI score (non renal lupus) at 24 & 48 weeks; Achieved highest remission rates of any global LN study at 48 weeks VCS well tolerated, AE, SAE and mortality consistent with other LN trials AURION (supportive proof of concept) Single-arm, twin center exploratory study assessing predictive value of an early reduction in proteinuria in subjects receiving voclosporin + SoC in patients with active LN UPCR at week 8 is highly predictive of renal response at 24 & 48 weeks Renal function remains stable and inflammatory markers continue to normalize AURORA (Phase III pivotal) 52-week global double-blind placebo controlled study to demonstrate that voclosporin added to SoC can increase overall renal response rates in the presence of extremely low steroids; Primary endpoint: Renal response (or CR) at 52 weeks 11

12 1:1 Randomization N=265 AURA Study Design: Phase IIB Study was designed to evaluate whether voclosporin added to SoC can increase speed of and overall remission rates in the presence of extremely low steroids Primary endpoint 24 weeks Secondary endpoint 48 weeks VOCLOSPORIN 23.7 mg bid VOCLOSPORIN 23.7 mg bid MMF 2 g + oral corticosteroids VOCLOSPORIN 39.5 mg bid VOCLOSPORIN 39.5 mg bid MMF 2 g + oral corticosteroids PLACEBO PLACEBO MMF 2 g + oral corticosteroids mg/daily mg/daily AURA - forced steroid taper mg/daily 5 mg/daily 2.5 mg/daily Week

13 AURA Key Inclusion Criteria & Outcome Measures KEY INCLUSION CRITERIA Diagnosis of SLE according to ACR criteria Biopsy proven LN [Class III, IV or Class V (alone or in combination w/class III or IV)] Proteinuria of 1.5 mg/mg OR 2 mg/mg* Indicative of highly active disease PRIMARY OUTCOME MEASURES The proportion of subjects achieving complete remission (CR) at 24 weeks CR is defined as: Confirmed urinary protein/creatinine ratio of 0.5 mg/mg Presence of sustained, low dose steroids ( 10mg prednisone from week 16-24) + Normal, stable renal function ( 60 ml/min/1.73m 2 or no confirmed decrease from baseline in egfr of 20%) No administration of rescue medications KEY SECONDARY OUTCOMES Partial Remission, Time to Remission, Time to Partial Remission, Durability of remission and extra-renal activity (SLEDAI) at 24 & 48 weeks * 2 mg/mg refers to Class V patients 13

14 AURA: Renal Response (Remission) Rates at 24 & 48 weeks First global trial in active LN to meet its primary endpoint; highest CR rates of any other global study in active LN Endpoint Treatment 24 weeks Odds ratio (95% CI) P-value* 48 weeks Odds Ratio (95% CI) P-value* Complete Remission (CR) 23.7mg VCS BID 33% 2.03 (1.01, 4.05) p= % 3.21 (1.68, 6.13) p<.001 Control 19% NA NA 24% NA NA Partial Remission (PR) 23.7mg VCS BID 70% 2.33 (1.68, 6.13) p= % 2.34 (1.27, 4.33) p=.007 Control 49% NA NA 48% NA NA *p-values are vs control group 14

15 AURA: Improved Renal Response Over Time with Voclosporin Patients achieving CR 23.7mg BID VCS demonstrates statistically significant renal response rates at 24 & 48 weeks Progression to Complete Remission Progression to any Renal Response 60% 50% p< % 70% 60% p=.007 p= % p= % 30% 40% 30% 20% 20% 10% 10% 0% 0% Baseline 24 weeks 48 weeks Control VCS 23.7mg BID Control VCS 23.7mg BID 15

16 AURA: Pre-specified Analysis: Speed of Remission (renal response) VCS showed a statistically significant faster speed of remission compared to the control group P-Value <0.001 for both LD-VCS and HD-VCS 16

17 AURA Pre-specified Analysis: UPCR (mg/mg) (Mean ± SD) Over Time UPCR (mg/mg) A statistically significant reduction in UPCR vs. patients in the control group; UPCR also remains stable after treatment stopped 10 9 UPCR (Mean ± SD) Over Time p< Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Week 50 Visit 17

18 AURA: Pre-specified Analysis: SELENA-SLEDAI Score 24 & 48 weeks VCS showed statistically significant reduction of SLEDAI score vs. patients in the control group Mean Change from Baseline in SELENA-SLEDAI Score Mean Change from Baseline at 24 weeks Mean Change from Baseline at 48 weeks p= p<.001 Control Voclosporin 23.7 mg BID 18

19 AURA Pre-specified Analysis: Anti-dS-DNA (Mean ± SD) Over Time dsdna Antibody (IU/mL) VCS showed statistically significant reduction of Ds-DNA antibody vs. patients in the control group Anti-dsDNA (Mean ± SD) Over Time p= Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Visit 19

20 AURA: Summary of TEAEs & Historical Comparison Treatment Emergent Adverse Events (TEAE)* *includes TEAES following treatment period Control N = 88 n (%) VCS 23.7 mg BID N = 89 n (%) VCS 39.5 mg BID N = 88 n (%) Any TEAE 78 (88.6) 82 (92.1) 85 (96.6) Any Serious TEAE 17 (19.3) 25 (28.1) 22 (25.0) Any TEAE with Outcome of Death 4 (4.5) 10 (11.2) 2 (2.3) Any Treatment-Related TEAE 15 (17.0) 45 (50.6) 55 (62.5) Any Serious Treatment-Related TEAE 1 (1.1) 4 (4.5) 7 (8.0) AURA-LV 4 N=265 (to Dec 18th/16) ALMS Induction 2 N=364 Abatacept Study 1 MMF N = 298 Ocrelizumab Study 3 N=378 SAE s, Subjects, n (%) 59 (22.3%) (25.3%) 92 (30.9%) 107 (28.3%) Serious Infections, Subjects n (%) 29 (10.9%) (10.9%) 58 (19.5%) 64 (16.9%) Deaths, Subjects, n (%) 13 (4.9%) 14 (3.8%) 14 (4.7%) 14 (3.7%) 1.Furie R. et al., Arthritis and Rheumatology, Vol. 66, No 2, February Appel GB, et al. J Am Soc Nephrol. 2009;20(5): Aspreva Lupus Management Study (Induction) 3.Mysler, E. et al., Arthritis and Rheumatism, Vol. 65, No 9, September 2013, AURA-LV Study results Aurinia data on file 20

21 AURA: Renal Function: egfr (ml/min/1.73m²) over time Renal function remains stable throughout treatment period; egfr returns to baseline after 48 weeks 21

22 AURA: Blood Pressure (BP) (Mean ± SD) over 48 weeks Diastolic Blood Pressure (mmhg) Systolic Blood Pressure (mmhg) No significant difference in blood pressure over the 48-week treatment period Systolic BP (Mean ± SD) Over Time Baseline Day 1 Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Visit Diastolic BP (Mean ± SD) Over Time Week Baseline Day 1 Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Visit 22

23 AURA Top-line Safety Summary No new safety signals were observed with the use of voclosporin in LN patients; voclosporin was well-tolerated The overall safety profile is consistent with other immunomodulators 13 deaths have been reported in the AURA study: pattern is consistent with other global Active LN studies 1,2,3 11 of 13 deaths occurred at sites with compromised access to standard of care and all deaths were determined to be unrelated to study treatment; no dose-dependent relationship was observed Safety beyond 24 weeks Control N = 88 n (%) VCS 23.7 mg BID N = 89 (n %) Any Serious Adverse Event 1 (1.1)^ 2 (2.2) Malignancies 1 (1.1)^ 0 (0) Deaths 3 (3.4)* 0 (0) In previous studies (other indications), >2000 patients have been treated with voclosporin with no abnormal or unexpected SAE s this remains the case upon review of the AURA data 1 Furie R. et al., Arthritis and Rheumatology, Vol. 66, No 2, February Appel GB, et al. J Am Soc Nephrol. 2009;20(5): Aspreva Lupus Management Study (Induction) 3.Mysler, E. et al., Arthritis and Rheumatixm, Vol. 65, No 9, September 2013, ^Malignancy (metastatic melanoma) occurred following treatment period *3 deaths occurred following the treatment period (after week 50) 23

24 AURA: Conclusions First therapeutic agent to meet ALL KEY 24 & 48 week pre-specified secondary endpoints in global clinical trial for active LN EFFICACY 23.7mg BID voclosporin demonstrated a statistically significant: Higher CR vs. the control group at weeks 24 (p=.045); & 48 (p<.001) Higher PR (50% reduction in UPCR over baseline) at weeks 24 & 48 (p=.007 & p=.002) Faster time to CR (UPCR 0.5mg/mg) (p=.002) Faster time to PR (p=.001) Reduction in UPCR (both FMV & 24hr urine) at weeks 24 (p<.01) & 48 weeks (p<.001) Reduction in SLEDAI at 24 (p=.003) & 48 weeks (p<.001) SAFETY No new safety signals were observed with the use of VCS in LN patients & voclosporin was welltolerated Across indications, >2200 patients have been treated with VCS with no abnormal or unexpected SAEs 24

25 AURION: Study Design Single-arm, twin center exploratory study assessing predictive value of an early reduction in proteinuria in subjects receiving voclosporin (23.7 mg BID) + SoC in patients with active LN Exploratory endpoint, 8 weeks 24 week assessment End of study, 48 weeks N = 10 SCREENING VOCLOSPORIN 23.7 mg bid VOCLOSPORIN 23.7 mg bid MMF 1 2 g + oral corticosteroids Primary analysis: Number of patients achieving each of the following biomarkers and the number of these patients who go on to achieve week 24 or week 48 remission. Biomarkers: 25% reduction in urinary protein creatinine ratio (UPCr) at 8 weeks C3 normalization at 8 weeks C4 normalization at 8 weeks Anti-dsDNA normalization at 8 weeks Secondary analyses: 24, 48 week outcomes, markers of SLE, PK/PD voclosporin in LN subjects C3, complement 3; C4, complement 4; anti-dsdna, anti-double-stranded DNA. 25

26 AURION & AURA Predictive Response at 24 & 48 weeks UPCR at week 8 is highly predictive of renal response at 24 & 48 weeks Biomarker AURION AURA Week 24 Week 48 Week 24 Week 48 25% reduction in week 8 UPCR C3 Normalization C4 Normalization Anti-dsDNA Normalization sensitivity 71% 75% 100% 91% specificity 33% 24% 30% 31% sensitivity 29% 25% 15% 22% specificity 100% 75% 82% 88% sensitivity 29% 25% 40% 30% specificity 100% 75% 90% 91% sensitivity 57% 50% 13% 18% specificity 100% 50% 54% 50% 26

27 AURION: egfr (CKD-EPI: Mean ± SE) Safety Population (All patients) Renal function remains stable through 48 weeks VCS completed at 48 weeks Baseline Week 2 Week 4 Week 8 Week 12 Week 24 Week 36 Week 48 Week 50 egfr

28 AURION: Role of Biomarkers as Predictors of Remission 25% Reduction in UPCR from baseline offers high sensitivity, but low specificity C 3 and C 4 normalization offer low sensitivity and high specificity; Anti-dsDNA offers little additional information Post-hoc analysis of AURA demonstrates similar results Future studies in LN utilizing predictive biomarkers should consider both 25% reduction in UPCR and C 3 /C 4 normalization 28

29 Voclosporin Potential to Address LN Critical Need LN Critical Need Voclosporin (based on top-line AURA 48-week results) Control of Active Disease Rapid Disease Control Lower Steroid Burden Convenient Treatment Regimen 29

30 Overview of Regulatory discussions Voclosporin has FDA Fast-track designation Comprehensive package of clinical data to date submitted and reviewed by the Division of Pulmonary, Allergy & Rheumatology at FDA, European Medicines Agency (EMA) and Pharmaceutical & Medical Devices Agency (PMDA) in Japan Pursuant to regulatory interactions, we are conducting a single Phase III trial (AURORA) to serve as basis for regulatory submissions in major markets US, Europe, and Japan 30

31 1:1 Randomization N~320 Continuation Study AURORA Study Design: Phase III-nearly identical to AURA 52-week global double-blind placebo controlled study to demonstrate that voclosporin added to SoC can increase overall renal response rates in the presence of extremely low steroids; Primary endpoint: Renal response (or CR) at 52 weeks data expected late 2019 Secondary endpoint 24 weeks Primary endpoint 52 weeks VOCLOSPORIN 23.7 mg bid VOCLOSPORIN 23.7 mg bid MMF 2 g + oral corticosteroids Treatment arm PLACEBO PLACEBO MMF 2 g + oral corticosteroids Control arm mg/daily mg/daily Forced steroid taper mg/daily 5 mg/daily 2.5 mg/daily Week

32 Commercial Prospects for Voclosporin Treated LN Population* K K Quality of diagnosis by referring physicians* In US and EU, 1 in 5 lupus nephritis patients are thought to be undiagnosed due to referring physicians being inefficient and inaccurate in diagnosing the condition. Controlled Poorly controlled Active disease Current proportion of controlled vs uncontrolled pts* Maintenance Induction 58% 25% 17% When surveyed, physicians would use this product for both maintenance and induction phases Frequency of visit* Every 3 months Every 1-2 months > Once a month Current treatment* Hydroxychloroquine, MMF, and steroids are most commonly used in the largest shares of patients. Satisfaction* Only 18% of physicians were very satisfied or extremely satisfied with currently available therapies ability to achieve a CR within 6 months *Aurinia market research conducted in 2016 with ~700 Rheumatologists and Nephrologist across Europe and the United States 32

33 LN Cycle of Disease Process & Flare Rates* Destructive Cycle of LN Frequency of LN Flares* FLARE INDUCTION IVC or MMF with high dose steroids REMISSION ~ 700 Rheumatologists & Nephrologists Surveyed across US & EU steroid taper MMF or AZA MAINTENANCE steroid taper Mean Frequency of LN Flare ~ every 14 months *Aurinia market research conducted in 2016 with ~700 Rheumatologists and Nephrologist across Europe and the United States 33

34 Potential Peak Sales by Market Initial estimates of Voclosporin peak sales yield global opportunity in excess of $1billion Japan Over $80million Japan population and competitive market offers smaller opportunity EU population likely larger than US however pricing opportunity is more limited EU Over $300million US market will provide most opportunity Population, pricing potential and physician adoption of treatment support strong sales prospects US Over $1billion 34

35 Milestones Q Japanese Phase I ethno bridging study results Q AURA-LV 48-week top-line secondary endpoint results Q AURION 48-week results Q AURA-LV 48-week full data scientific & medical presentations Q Outcome of EMA & PMDA discussions Q Initiation of Phase III program - AURORA 35

36 Investment Summary MANAGEMENT WITH TRACK RECORD OF SUCCESS & EXTENSIVE EXPERTISE IN LN SOLID CLINICAL DOSSIER Positive PoC and Phase IIB study results Positive interactions with regulatory authorities >2,200 patients treated with voclosporin to date (across indications) well-characterized safety profile Only one Phase III clinical trial required by the FDA prior to a NDA submission LARGE AND WELL-DEFINED MARKET OPPORTUNITY >$1B Extremely high pharmaco-economic burden LN patients appear to be readily assessable and easily identified by specialty treaters STRONG CASH POSITION ~$200M as of March 31,

37 THANK YOU # Markham Street Victoria BC V8Z 7X8