Corporate Presentation

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1 Corporate Presentation January

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-in-class 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 AURORA study; the anticipated commercial potential of voclosporin for the treatment of LN, FSGS, and Dry Eye; and anticipated interactions with the US Food and Drug Administration, including potential dates for submission and approval of marketing applications, and product label. 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 forward-looking 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 forward-looking 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 forwardlooking 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 Late-stage clinical biopharma 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) Highly differentiated, next-generation CNI w/fast-track designation, strong IP, and potential to be used in multiple indications Lead Program is in Phase 3 for treatment of LN w/significant Phase 2 data Additional indications in Phase 2 3

4 Reaching People & Changing Lives Our mission is to develop & deliver treatments to people living w/debilitating diseases Product & Indication Development Stage Phase 1 Phase 2 Phase 3 Market Voclosporin Lupus Nephritis (LN) Voclosporin Focal Segmental Glomerulosclerosis (FSGS) VOS (Voclosporin ophthalmic solution) Dry Eye Syndrome (DES)* *also known as dry eye disease (DED) and keratoconjunctivitis sicca (KCS) 4

5 SLE & LN Overview & Symptomatology Systemic Lupus Erythematosus (SLE) is a chronic, complex and often disabling autoimmune disorder Affects over ~445K people in the US (mostly women) 1 CENTRAL NERVOUS SYSTEM LUNGS HEART Highly heterogeneous, affecting range of organ & tissue systems 1 Headaches, dizziness, memory disturbances, vision problems, seizures, stroke, or changes in behavior Pleuritis, inflammation, or pneumonia Chest pains, heart murmurs LN is an inflammation of the kidneys caused by SLE & represents a serious progression of SLE Up to 50% of SLE patients develop LN 2 Leakage of blood proteins into the urine (proteinuria) is clinical sign of LN 2 Straightforward disease outcomes: an early response, which can be assessed by measuring proteinuria correlates w/long-term outcomes KIDNEYS Inflammation BLOOD Anemia, decreased white cells, increased risk of blood clots WIDESPREAD Fatigue, fever, joint pain, muscle aches, photosensitivity, rashes, hair loss, anxiety & depression Debilitating & costly, often leading to ESRD, dialysis, renal transplant, & death 2 As many as 30% of LN patients will progress to ESRD 3! NO FDA OR EMA APPROVED LN THERAPIES 1. The MarketScan Research Databases, Truven Health Analytics 2. NIDDK, Lupus Nephritis. 3. Update on Lupus Nephritis, Almaani et al. JASN May 2017, 12 (5)

6 The Severity of Lupus Nephritis SLE patients w/renal damage and ESRD have 14-fold & >60-fold increased risk of premature death, respectively 1 Standardized Mortality Ratio All SLE patients SLE patients w/o renal disease SLE w/renal disease SLE w/renal damage SLE w/ckd stage 3 & 4 SLE w/esrd SLE w/renal disease (no renal biopsy) Proliferative LN Pure membranous LN Proliferative LN w/renal damage Proliferative or membranous LN w/renal damage Mok et al, Arthritis Rheum 2013 SMR 6

7 Cost Burden of Lupus Nephritis SLE patients with LN have ~3x the expenditure of SLE patients without nephritis Average Annual Cost of Illness per Patient by Condition 1 $0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 Asthma Hypertension Diabetes COPD Cost of Dialysis for Glomerulonephritis: ~$80K annually 2 Bipolar Disorder Heart Disease Rheumatoid Arthritis Ulcerative Colitis Crohns Disease SLE (no nephritis) Cost of Kidney Transplant: ~$414K 3 Lupus Nephritis Medical Costs Absence Costs Short Term Disability 1. Carls G, et al. J Occup Environ Med. 2009;51: USRDS United Network for Organ Sharing (UNOS) Transplant Report

8 Dollars Can t Capture the Patient Experience Recent patient feedback from the Lupus Patient Focused Drug Development meeting with FDA highlights desire for better QoL and less steroids Cardiovascular Issues Osteoporosis & Fractures Steroid Burden Infections Glaucoma & Cataracts Emotional Issues 8

9 Getting Disease into Remission Quickly Is Key Destructive Cycle of LN Outcomes Based on Response 1 INDUCTION 100% 90% 80% 8% 70% 57% FLARE IVC or MMF w/highdose steroids MMF or AZA REMISSION 60% 50% 40% 92% 87% 30% MAINTENANCE 20% 10% 0% 43% 13% Remission Responder Non-Responder Not on 10 years On Dialysis at 10 years 1. Chen et al. Clin J. Am Soc Neph. 2008: Response = 50% reduction in proteinuria Remission = Proteinuria <.33g/24hrs 9

10 Voclosporin Potential to Address LN Critical Need LN Critical Need Voclosporin (based on AURA-LV Phase 2 study, 48-week results) Control of Active Disease Rapid Disease Control Reduced Steroid Burden Convenient Treatment Regimen 10

11 Voclosporin (VCS) Overview Voclosporin is a novel CNI that may offer a number of advantages over the legacy CNI options (cyclosporine A {CsA} and tacrolimus) Calcineurin inhibitors (CNIs) have demonstrated efficacy for a number of conditions, including transplant patients, lupus nephritis (LN) patients, keratoconjunctivitis sicca (dry eye) & other autoimmune diseases; however side effects exist which can limit their long-term use. Predictable concentration effect and tight PK/PD relationship no therapeutic drug monitoring 1,3 Better glucose profile (reduced diabetes risk) versus tacrolimus 2 Increased potency & improved lipid profile vs CsA 1 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 11

12 VCS in Renal Disease: Two Separate Mechanisms of Action 1 Inhibition of calcineurin reduced cytokine activation of t-cells 2 Potential disease-modifying podocyte stabilization, which protects against proteinuria voclosporin voclosporin Actin cytoskeleton APC Cytoplasm T cell receptor Nucleus Calcineurin IL-2 INF-gamma TNF-alpha Cellmediated immune response Dephosphorylation of synaptopodin by calcineurin leads to synaptopodin release from actin filaments which leads to actin degradation Tissue damage Glomerular basement membrane APC=Antigen-presenting cell; INF=Interferon; IL=Interleukin; LN=Lupus nephritis; NFAT=Nuclear factor of activated T cells; TNF=Tumor necrosis factor 12

13 Voclosporin LN Clinical Program Completed Trials AURA-LV (AURA) (Phase 2) AURION (Phase 2 Proof of Concept) Statistically significant higher CR, PR, time to CR/PR, UPCR reduction & SELENA-SLEDAI at Weeks 24 & 48; Achieved highest remission rates of any global LN study at 48 weeks (49.4%, p<.001) The overall safety profile was consistent with the expectations for the class of drug, the patient population, & concomitant therapies UPCR at Week 8 is highly predictive of renal response at Weeks 24 & 48 Renal function remained stable, inflammatory markers continue to normalize; & no unexpected safety signals AURORA (Phase 3) Ongoing AURORA 2 (Extension Study) Double-blind placebo controlled study to show if VCS w/background MMF/CellCept can increase speed of & overall remission rates in presence of low steroids Primary endpoint: Renal response (or CR) at 52 weeks 2-year blinded extension study to collect long-term data of voclosporin in LN Not required for regulatory approval CR=Complete remission; PR=Partial remission; Safety of Estrogens in Lupus Erythematosus National Assessment ; (SELENA)-Systemic Lupus Erythematosus Disease Activity Index; (SLEDAI); UPCR=Urine protein creatinine ratio; VCS=Voclosporin 13

14 Mg/daily AURA Study Design: Phase 2 Study was designed to evaluate whether voclosporin in combination w/background MMF/CellCept can increase speed of & overall remission rates in the presence of low steroids Primary endpoint: Complete Remission (or renal response) at 24 weeks Primary endpoint 24 weeks Secondary endpoint 48 weeks VOCLOSPORIN 23.7 mg bid VOCLOSPORIN 23.7 mg bid MMF 2 g + oral corticosteroids 1:1 Randomization N=265 VOCLOSPORIN 39.5 mg bid MMF 2 g + oral corticosteroids VOCLOSPORIN 39.5 mg bid PLACEBO PLACEBO MMF 2 g + oral corticosteroids Rapid steroid taper Week

15 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 1.5 mg/mg OR 2 mg/mg* Indicative of highly active disease * 2 mg/mg refers to Class V patients Primary Outcome Measures The proportion of subjects achieving complete remission (CR) at 24 weeks CR is defined as: Urinary protein creatinine ratio of 0.5 mg/mg Presence of sustained, low dose steroids ( 10mg prednisone from Week 16-24) + egfr 60 ml/min/1.73m 2 or no confirmed decrease from baseline in egfr of 20% No administration of rescue medications Key Secondary Outcomes CR at 48 weeks, Partial Remission, Time to Remission, Time to Partial Remission, Durability of remission, & SLEDAI at 24 & 48 weeks 15

16 AURA: Renal Response (Remission) Rates at Weeks 24 & 48 First global trial in active LN to meet its primary endpoint; highest CR rates of any 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% 39.5mg VCS BID 27% 2.03 (1.01, 4.05) 1.59 (0.78, 3.27) p= % p= % 3.21 (1.68, 6.13) 2.10 (1.09, 4.02) p<.001 p=.026 Control 19% NA NA 24% NA NA Partial Renal Response/ 50% reduction in UPCR (PR) 23.7mg VCS BID 70% 39.5mg VCS BID 66% 2.33 (1.68, 6.13) 2.03 (1.10, 3.76) p= % p= % 2.34 (1.27, 4.33) 2.68 (1.43, 5.02) p=.007 p=.002 Control 49% NA NA 48% NA NA *Phase 3 dose is 23.7mg BID 16

17 dsdna Antibody (IU/mL) UPCR (mg/mg) AURA: Reduction in UPCR & Anti-dsDNA (Mean) Over Time VCS 23.7mg BID* demonstrates statistically significant reduction in UPCR & Anti-dsDNA vs patients in the control group at 24 & 48 weeks; UPCR also remains stable after tx stopped UPCR (Mean) Over Time p<.001 p<.001 Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Week 50 Visit Anti-dsDNA (Mean ± SD) Over Time p=.006 p=.006 Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Visit *Data only shown for Phase 3 dose (23.7mg BID) 17

18 AURA: Mean Reduction in Baseline SELENA-SLEDAI* Score VCS 23.7mg BID** showed statistically significant mean reduction of baseline SELENA-SLEDAI score vs subjects in the control group at weeks 24 and Baseline Mean Change from Baseline to Week 24 Week 24 Week 48 Mean Change from Baseline to Week **Data only shown for Phase 3 dose (23.7mg BID) Control p=.003 voclosporin 23.7mg BID -7.9 p<.001 *Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 18

19 egfr (ml/min/1.73m²) AURA Pre-Specified Analysis: Renal Function egfr over time Renal function remains stable throughout treatment period (no statistically significant difference); egfr returns to baseline after 48 weeks 100 egfr (ml/min/1.73m²) (Mean) Over Time Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 26 Week 36 Week 48 Week 50 Visit Treatment Complete at week 48 *Data only shown for Phase 3 dose (23.7mg BID) Note: Per DSMB, this chart shows raw egfr values corrected so that values >90 ml/min/1.73 m 2 were rounded to 90 ml/min/1.73 m2 (i.e., corrected egfr). Source: Figure PH. 19

20 Diastolic Blood Pressure (mmhg) Systolic Blood Pressure (mmhg) AURA: Blood Pressure (BP) over 48 Weeks No statistically significant difference in blood pressure over the 48-week treatment period 140 Systolic BP (Mean) Over Time Baseline Day 1 Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Visit Week 48 Diastolic BP (Mean) Over Time Baseline Day 1 Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Visit *Data only shown for Phase 3 dose (23.7mg BID) 20

21 AURA: Summary of Adverse Events The overall safety profile & incidence of serious adverse events was consistent w/the expectations for the class of drug, the patient population, & concomitant therapies Adverse Event (AE) Summary Control N = 88 n (%) VCS 23.7 mg BID N = 89 n (%) Any AE 1 78 (88.6) 82 (92.1) Any Serious AE (SAE) 1 17 (19.3) 25 (28.1) Any AE w/outcome of death 2 4 (4.5) 10 (11.2) Any Treatment-Related AE w/outcome of death 0 (0.0) 0 (0.0) Any Treatment-Related AE 15 (17.0) 45 (50.6) Any Serious Treatment-Related AE 1 (1.1) 4 (4.5) Any AE Leading to Study Drug Discontinuation 9 (10.2) 16 (18.0) Any AE Leading to Study Drug Discontinuation (excluding deaths) 3 8 (9.2) 11 (12.4) *Data only shown for Phase 3 dose (23.7mg BID) Note: data shown is for treatment-emergent adverse events (i.e., AEs post randomization). 1. Data during study treatment period only; does not include the three placebo-randomized subjects that died post-study completion 2. Data includes three placebo-randomized subjects that died post-study completion. 3. For Any AE leading to Study Drug Discontinuation (excluding deaths) denominators are N=87 for control arm and N=79 for VCS 23.7 mg BID arm 21

22 AURA: Results Summary First therapeutic agent to meet the primary endpoint in a global clinical trial for active LN; trial also met key secondary endpoints at 24 & 48 weeks Full results published in Kidney International, the official journal of the International Society of Nephrology Efficacy Voclosporin 23.7mg BID (vs control) demonstrated a statistically significant: Higher CR at weeks 24 (p=.045) and 48 (p<.001) Higher PR (50% reduction in UPCR over baseline) at weeks 24 (p=.007) and 48 (p=.007) Faster time to CR (UPCR 0.5mg/mg) (p=.002) and PR (p=.001) Reduction in UPCR at weeks 24 (p<.01) and 48 (p<.001) Reduction in SLEDAI at weeks 24 (p=.003) and 48 (p<.001) Safety Across indications more than 2400 patients have been treated w/vcs. No new safety signals attributed to VCS were observed in AURA LV; The overall safety profile & incidence of serious adverse events was consistent with the expectations for the class of drug, the patient population, & concomitant therapies; 13 deaths were reported; all but two deaths occurred in the low-gdp subgroup; the DSMB concluded that the higher incidence of deaths in the low-dose VCS group was attributable to factors predisposing subjects to fatal outcomes in the study & local imbalances in randomization 1. Rovin, B et al. Kidney International, 2.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) 4.Mysler, E. et al., Arthritis and Rheumatism, Vol. 65, No 9, September 2013,

23 Mg/daily 2-Year Blinded Extension Study AURORA Phase 3 Study Design Mimics AURA Phase 2 Global, double-blind, placebo controlled study to evaluate whether voclosporin in combination w/background MMF/CellCept can increase speed of & overall remission rates in the presence of low steroids Primary endpoint: Renal Response (or CR) at 52 weeks data expected YE 2019 Secondary endpoint 24 weeks Primary endpoint 52 weeks VOCLOSPORIN 23.7 mg bid VOCLOSPORIN 23.7 mg bid 1:1 Randomization N=358 PLACEBO MMF 2 g + oral corticosteroids PLACEBO MMF 2 g + oral corticosteroids Rapid steroid taper Week 23

24 AURORA Key Inclusion Criteria & Primary Endpoint The AURA Phase 2 & the AURORA Phase 3 study have nearly identical inclusion criteria & similar primary endpoint Inclusion Criteria Primary Endpointº confirming Renal Response at Week 52 Urinary months^ egfr 60 ml/min/1.73m 2 or no confirmed decrease from baseline in egfr of 20% * 2 mg/mg refers to Class V patients; ^Biopsy results over 6 months prior to screening must be reviewed with a medical monitor to confirm eligibility. ºprimary endpoint is a composite 24

25 AURORA Phase 3 Study Status Target enrollment of 324 patients was surpassed due to high patient demand with 358 subjects randomized in sites across 27 countries; Data expected YE

26 Ideal Commercial Opportunity Established community Reimbursement for value Underdeveloped market Aurinia & Voclosporin Limited competition Costly disease burden 26

27 Composition of Matter Patent Coverage Patent protection for voclosporin in the US is anticipated until at least October 2027 under the Hatch-Waxman Act and comparable laws in other countries and until April 2028 with pediatric extension TARGET US LAUNCH USA Isomeric Patents (Trans Formulation) Patent Term Extension (5 years) October 2027 Pediatric Extension (6 months) April 2028 EUROPE Isomeric Patents (Trans Formulation) Supplementary Protection Patent (5 years) Pediatric Extension (6 months) PTE/SPC can only be tagged onto one patent 27

28 FSGS Overview & Symptomatology Similar to LN, decreased integrity of the podocyte is a key feature of disease progression KIDNEYS Inflammation Incidence: >5400 patients FSGS each year in US 1 ~30% of NS patients have FSGS on biopsy Nephrotic syndrome (NS) is a collection of symptoms that indicate kidney damage Leakage of blood proteins into the urine (proteinuria) is clinical sign of FSGS NEPHCURE International Hyperlipidemia and Hypoalbuminemia Acute Kidney Injury Patients more susceptible to infection & embolism Straightforward disease outcomes: an early clinical response (measured by proteinuria) correlates w/long-term outcomes Lack of control or proteinuria results in ESRD, which means dialysis or kidney transplantation! NO FDA OR EMA APPROVED FSGS THERAPIES 1. NEPHCURE International _Understanding FSGS 28

29 Early Clinical Response Critical to Maintain Kidney Health in FSGS Early response correlates w/long-term outcomes; measured by proteinuria Rapid control & reduction of proteinuria increases kidney survival 1 1. Cattran et.al J. Am. Soc. Nephrol. 16: ,

30 Treatment Algorithm for Primary FSGS 1 Primary FSGS FSGS lesion All patients get RAS blockade +/- diuretics +/- statin Full dose corticosteroid Rx Prednisone 1mg/kg/day for 4-8 (if proteinuria decreasing up to 16 wks) Taper progressively over 3 months Remission Steroid resistance/toxicity CNI (start low and have upper limit)* Sustained Remission Stop Corticosteroids Monthly dipstick surveillance to detect possible relapse*** Steroid dependent Consider adding CNI & taper corticosteroids to minimum No response** Response group keep on CNI for 1-2 years & taper to minimum dose w/dipstick monitoring of proteinuria Accept partial remission in proteinuria 1 Adapted from: Bhadran Bose, and Daniel Cattran CJASN 2014;9: *CNI dose as per the KDIGO guidelines on GN. **See the text on options to consider in the management of nonresponders. ***See the text on how to manage relapse 30

31 FSGS Proof of Concept Study Design Study is designed to evaluate the safety and efficacy of voclosporin as a first-line therapy for FSGS 31

32 Dry Eye Syndrome (DES)* Overview DES is a chronic inflammatory disease characterized by irritation and inflammation that occurs when the eye s tear film is compromised by reduced tear production, imbalanced tear composition, or excessive tear evaporation High Unmet Medical Need >16M patients affected by DES in the US 1 Control of symptoms is inadequate w/currently approved therapies Disease incidence may be growing, independent of improved diagnosis Patient demand for better control of symptoms is increasing *Also referred to as Dry Eye Disease (DED) and keratoconjuctivitis sicca (KCS) 1 Farrand, Kimberly F. et al. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older American Journal of Ophthalmology, Volume 182,

33 Voclosporin Opthalmic Solution (VOS) Overview VOS is a unique, patented, aqueous, preservative-free, nanomicellar solution Vitamin E TPGS, Octoxynol-40 Calcineurin inhibition is a validated mechanism for the treatment of ocular surface disease; however, there is opportunity for potential improvement in the effectiveness by enhancing tolerability and onset of action and alleviating the need for repetitive dosing Studies completed in rabbit & dog models; licensing deal with Merck Animal Health for animal use Phase 1b study completed; Phase 2 ongoing IP to ~

34 VOS: Potential to be a Best in Class CNI for DES With potential advantages vs Restasis, VOS has the potential to be a well-differentiated & best in class CNI for the treatment of DES VOS is potentially 4 times more potent than CsA & VOS has a 4-fold higher concentration of API per drop than Restasis (.2% vs.05%) (clear solution vs microemulsion) VOS achieved high concentrations in the target tissues of the eye (shown in Rabbit model preclinical data) VOS demonstrated excellent tolerability in a Phase 1b study (irritation equivalent to pbo) and in a H2H preclinical comparison to Restasis VOS has the potential to be dosed once daily with a rapid onset of action (shown in Rabbit study) 34

35 VOS Phase 2 Clinical Trial Phase 2, multi-center, Investigator-masked, randomized, parallel-group study to evaluate the tolerability, efficacy and safety of VOS versus Restasis in subjects with mild to moderate DES; Enrollment complete with N=100; data available before end of January 2019 ^System Assessment in Dry Eye 35

36 Investment Summary 36

37 Milestones LN TARGET LAUNCH FSGS 37

38 Thank You 38