Corporate Presentation. February 2018

Transcription

1 Corporate Presentation February 2018

2 HQ: Victoria, British Columbia, Canada NASDAQ: AUPH TSX. AUP Founded by former members of the Aspreva Pharmaceuticals team Patient-focused late clinical stage biopharmaceutical company Targeting patient populations for which there is a high unmet medical need Highly experienced team with 35 full-time employees 2

3 Company Highlights Clinical-stage 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 with strong IP and potential to be used in multiple indications Lead Program is in Phase III for treatment of LN with significant Phase II data Additional indications entering Phase II STRONG CASH POSITION ~182M as of September 30,

4 Our mission is to develop & deliver treatments to people living with debilitating diseases Product Indication Development Stage Phase I Phase 2 Phase 3 Market Voclosporin Lupus Nephritis (LN) FSGS & MCD (Nephrotic Syndrome) VOS (ophthalmic solution) Dry Eye Syndrome (DES) 4

5 SLE & LN Overview & Symptomatology CENTRAL NERVOUS SYSTEM Headaches, dizziness, memory disturbances, vision problems, seizures, stroke, or changes in behavior LUNGS Pleuritis, inflammation, or pneumonia HEART Chest pains, heart murmurs KIDNEYS Inflammation 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 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 5

6 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

7 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 Colitis Crohns Disease SLE (no nephritis) Lupus Nephritis Medical Costs Absence Costs Short Term Disability * Carls G, et al. J Occup Environ Med. 2009;51:

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

9 Dollars Can t Capture the Patient Experience Recent patient feedback from Lupus Patient Focused Drug Development meeting with FDA confirms desire for better QOL and less steroids Cardiovascular Issues Osteoporosis and Fractures Steroid Burden Infections Glaucoma and Cataracts Emotional Issues 9

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

11 Voclosporin Overview Voclosporin (VCS) is a novel CNI that may offer a number of advantages over the legacy CNI options (cyclosporine A {CsA} and tacrolimus) Predictable concentration effect and tight PK/PD relationship no therapeutic drug monitoring 1,3 Better glucose profile versus tacrolimus 2 Increased potency & improved lipid profile vs CsA 1 Calcineurin inhibitors (CNIs) have demonstrated efficacy for a number of conditions, including transplant patients, lupus nephritis (LN) patients, keratoconjunctivitis sicca (dry eye) and other autoimmune diseases; however side effects exist which can limit their long-term use LN, lupus nephritis; CNI, calcineurin inhibitor; MMF, mycophenolate mofetil; PK/PD, pharmacokinetics/pharmacodynamics. 1. Aurinia Data on file 3. AURA-LV Data on file 2. Busque S, et al. Am J Transplant. 2011;11(12): & AURA LV Data 11

12 The Activity of VCS in Renal Disease Involves 2 Separate Mechanisms 1 Inhibition of calcineurin reduced cytokine activation 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 Dephosphorylated synaptopodin breaks up and destabilizes the actin cytoskeleton of the podocyte Tissue damage Glomerular basement membrane LN, lupus nephritis; NFAT, nuclear factor of activated T cells; APC, antigen-presenting cell; IL, interleukin; INF, interferon; TNF, tumor necrosis factor. 12

13 Voclosporin LN Clinical Program AURA-LV (Phase IIb) AURION (Proof of Concept) Statistically significant higher CR, PR, time to CR/PR, UPCR reduction & SLEDAI at 24 & 48 weeks; Achieved highest remission rates of any global LN study at 48 weeks (49.4%, p<.001) AE, SAEs & overall trial mortality consistent with other global LN trials 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) Double-blind placebo controlled study to demonstrate that VCS added to SoC can increase overall renal response rates in the presence of extremely low steroids; 2-year Extension Study Primary endpoint: Renal response (or CR) at 52 weeks Drug-Drug Interaction (DDI) Study (Phase 1) Healthy volunteers (US or Canada) 2 weeks of treatment (14 days MMF, 7 days VCS) Assessments: Bloodwork, PK sampling, and other assessments at various timepoints 13

14 1:1 Randomization N=265 AURA-LV 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: 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 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 Rapid steroid taper mg/daily 5 mg/daily 2.5 mg/daily Week

15 AURA-LV 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: 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 CR at 48 weeks, Partial Remission, Time to Remission, Time to Partial Remission, Durability of remission, and SLEDAI at 24 & 48 weeks * 2 mg/mg refers to Class V patients 15

16 Patients achieving CR AURA-LV: Complete Remission (CR) Rates at 24 & 48 Weeks 23.7mg BID* VCS demonstrates statistically significant CR rates at 24 & 48 weeks 60% 50% Progression to Complete Remission p< mg BID Control 24 week CR 32.6% 19.3% 40% p=.045 Odds Ratio (OR); p-value 2.03; p= % 20% Improving delta over time 48 week CR 49.4% 23.9% Odds Ratio (OR); p-value 3.21; p< % 0% Baseline 24 weeks 48 weeks Control Low Dose *23.7mg is Phase III dose, so 39.5mg not shown here 16

17 AURA-LV: Improved Remission Over Time with Voclosporin VCS 23.7mg BID* demonstrates statistically significant complete and partial remission (renal response) rates at 24 & 48 weeks 80% ppr Control CR ppr=pr - CR PR=pPR + CR 27.3mg BID VCS ppr CR PR=70% PR=69% 60% 20% 40% PR= 49% 30% PR=48% 24% 37% p< % subjects in CR at 24 weeks remain in CR at 48 weeks 20% 19% 24% 33% 49% 0% *23.7mg is Phase III dose, so 39.5mg not shown here Week 17

18 AURA-LV: Pre-specified Biomarker Analyses: UPCR (mg/mg) and Anti-dsDNA (Mean) Over Time dsdna Antibody (IU/mL) UPCR (mg/mg) VCS 23.7mg BID demonstrates statistically significant reduction in UPCR & AntidsDNA vs patients in the control group; UPCR also remains stable after tx stopped 10 8 UPCR (Mean) Over Time 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 Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24 Week 48 Visit 18

19 AURA-LV: Pre-specified Analysis: SELENA-SLEDAI Score 24 & 48 weeks VCS showed statistically significant reduction of SLEDAI score vs. patients in the control group Baseline Mean Change from Baseline to Week 24 Week 24 Week 48 Mean Change from Baseline to Week Control p=.003 Voclosporin 23.7mg BID -7.9 p<

20 AURA-LV: Renal Function: egfr (ml/min/1.73m²) over time Renal function remains stable throughout treatment period; egfr returns to baseline after 48 weeks 100 egfr (Mean) Over Time egfr (ml/min/1.73m²) 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 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. 20

21 Diastolic Blood Pressure (mmhg) Systolic Blood Pressure (mmhg) AURA-LV: Blood Pressure (BP) over 48 weeks No significant difference in blood pressure over the 48-week treatment period 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 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 21

22 AURA-LV: Summary of Adverse Events & Historical Comparison Adverse Event (AE) Summary Control N = 88 n (%) VCS 23.7 mg BID N = 89 n (%) Any AE1 78 (88.6) 82 (92.1) Any Serious AE (SAE) 1 17 (19.3) 25 (28.1) Any AE with Outcome of death1 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) 2 8 (9.2) 11 (12.4) Note: data shown is for treatment-emergent adverse events (i.e., AEs post randomization). 1. Data includes three placebo-randomized subjects that died post-study completion. 2. 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. AURA-LV 5 N=265 n (%) (48 weeks) ALMS Induction 3 N=370 n(%) (24 weeks) Abatacept Study 2 N = 298 n(%) (52 weeks) Ocrelizumab Study 4 N=378 n(%) (48 weeks) SAE s, Subjects, n (%) 61 (23.0) 92 (25.3) 92 (30.9) 107 (28.3) Serious Infections, Subjects n (%) 30 (11.3) 40 (10.9) 38 (19.5) 64 (16.9) Deaths, Subjects, n (%) 13 (4.9) 1 14 (3.8) 14 (4.7) 14 (3.7) 1. Data during study treatment period only; does not include the three placebo-randomized subjects that died post-study completion. 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, AURA-LV Study results Aurinia data on file 22

23 AURA-LV: Results Summary First therapeutic agent to meet the PRIMARY endpoint and key 24- and 48-week pre-specified secondary endpoints in a global clinical trial for active LN EFFICACY Voclosporin 23.7mg BID (vs control) demonstrated a statistically significant: Higher CR vs. 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) Faster time to 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 No new or unexpected safety signals were observed with the use of VCS in LN patients; voclosporin was well-tolerated over a 48-week period. The overall safety profile was consistent with the expectations for the class of drug, the patient population, and concomitant therapies. Across indications, >2,400 patients have been treated with VCS with no new or unexpected SAEs. 23

24 1:1 Randomization N= Year Extension Study AURORA Study Design: Phase III Mimics AURA Phase IIb 52-week global, double-blind, placebo-controlled study to evaluate whether voclosporin added to SoC can increase overall renal response rates in the presence of 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 MMF 2 g + oral corticosteroids Treatment arm PLACEBO MMF 2 g + oral corticosteroids Control arm mg/daily Rapid steroid taper mg/daily mg/daily 5 mg/daily 2.5 mg/daily Week

25 AURORA Key Inclusion Criteria & Primary Endpoint The AURA-LV Phase IIb and the AURORA Phase III study have nearly identical inclusion criteria and similar primary endpoint Inclusion Criteria Primary Endpoint^ Diagnosis of SLE according to ACR criteria Kidney biopsy within 24 months^ of study entry confirming histologic diagnosis of LN Biopsy proven LN [Class III, IV or Class V (alone or in combination w/class III or IV)] Renal Response at week 52 Urinary protein/creatinine ratio (UPCR) of 0.5 mg/mg * 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. ^primary endpoint is a composite Proteinuria of 1.5 mg/mg OR 2 mg/mg* + Normal, stable renal function ( 60 ml/min/1.73m 2 or no confirmed decrease from baseline in egfr of >20%) + Presence of sustained, low dose steroids ( 10mg prednisone from week 16-24) + No administration of rescue medications 25

26 AURORA Phase III Study Status* Number of sites initiated 62 USA / 48 Canada 76 EU/ CIS/Africa APAC 14 LATAM MAJORITY of US sites activated 26 out of 29 Countries have sites initiated Investigator Meetings Completed Miami, FL, USA Madrid, Spain Bangkok, Thailand Osaka, Japan Panama City, Panama Cape Town, South Africa Belgrade, Serbia Sao Paolo, Brazil *as of January 5,

27 LN Clinical & Regulatory Timelines 1H H H H H H H 2021 DDI Study AURORA Recruitment Complete AURORA Data AURORA Extension Study Rolling NDA Submission Non-Clinical Section CMC Section Clinical Section Projected FDA AdCom Potential Approval Clinical Regulatory TARGET LAUNCH 27

28 Ideal Commercial Opportunity Building Relationships Additive vs. Established community Displacement Positioning Product Reimbursement for Value Reimbursement for value Established Underdeveloped market Market Aurinia & Voclosporin & VOCLOSPORIN Pricing Assessment Limited Competition Limited competition Costly Disease Burden Costly disease burden Identifying Targets 28

29 Market Opportunity Initial estimates of voclosporin peak sales potential in lupus nephritis yield global opportunity of $1.4 billion+ 29

30 Renal Franchise Expansion A number of renal diseases are characterized by proteinuria Reduction in proteinuria correlates with long-term outcomes for renal diseases Legacy CNIs are effective in reducing proteinuria in renal diseases Voclosporin may have a number of advantages over legacy CNIs MAXIMIZE VOCLOSPORIN S VALUE 30

31 Nephrotic Syndrome (NS) Overview & Symptomatology ~50% of NS patients have FSGS or MCD on biopsy 1 ; ~60,000 patients in the US Nephrotic syndrome is a collection of symptoms that indicate kidney damage KIDNEYS Inflammation Proteinuria large amounts of protein in the urine Hyperlipidemia higher than normal fat and cholesterol levels in the blood Acute Kidney Injury Hypoalbuminemia low levels of albumin in the blood Edema, or swelling, usually in the legs, feet, or ankles and less often in the hands or face Patients more susceptible to infection and embolism Integrity of the podocyte is key feature of disease progression Straightforward disease outcomes early response correlates with long term outcomes; measured by proteinuria Lack of control of proteinuria results in End Stage Renal Disease, which means dialysis or kidney transplantation! NO FDA OR EMA APPROVED THERAPIES FSGS or MCD 1 NephCure Registry

32 Early Clinical Response is Critical to Maintaining Long-Term Kidney Health in FSGS Rapid control & reduction of proteinuria increases kidney survival 1 1. Cattran 1. Cattran et.al et.al J. J. Am. Soc. Nephrol. Nephrol. 16: , 16: ,

33 FSGS/MCD Proof of Concept Potential Study Design Study is designed to evaluate the safety and efficacy of voclosporin as a first-line therapy for FSGS/MCD Projected Interim data readout(s) 6 months Primary Endpoint N=~20 VOCLOSPORIN 23.7 mg bid Q KEY INCLUSION CRITERIA Biopsy proven FSGS or MCD Proteinuria of 3 mg/mg Corticosteroid-Free PRIMARY OUTCOME MEASURE The proportion of subjects achieving complete or partial remission at 6 months CR is defined as: Urinary protein/creatinine ratio of 0.3 mg/mg PR is defined as 50% reduction in Urinary protein/creatinine ratio 33

34 Voclosporin Ophthalmic Solution (VOS): A New Product Unique aqueous, preservative free nanomicellar solution (voclosporin 0.2%) To be used in the treatment of Dry Eye Syndrome, impacting >20 million patients in the United States Additional animal safety toxicology studies planned. Studies already completed in rabbit and dog models Additional human clinical trials planned Phase 1 study already completed IP to ~

35 Dry Eye Syndrome (DES) Unmet Need DES is an Inflammatory Disease Cure is rare or non-existent Control of symptoms is inadequate with currently available Rx Disease incidence may be growing, independent of improved diagnosis Aging population, increasing incidence with age, menopause Growth of prostaglandin / other eye drop Rx for glaucoma Increasing patient demand for better control of symptoms Growth of premium IOL cataract surgery, with increased insistence on high grade vision after more expensive surgery 35

36 VOS: Potential to Be a Low Risk, High Reward Project Voclosporin Ophthalmic Solution (VOS) incorporates a unique & patented nanomicellar formulation system with potential clinical advantages vs. Restasis VOS is ~4 times more potent than CsA and VOS has a 4-fold higher concentration of API per drop than Restasis (clear solution vs. microemulsion) VOS achieved high concentrations in the target tissues of the eye (Rabbit model preclinical data) VOS has demonstrated excellent tolerability in a H2H preclinical comparison to Restasis & in a Phase 1 study irritation equivalent to placebo VOS has the potential to be dosed once daily with a rapid onset of action (Rabbit study) VOS has the potential to be a well differentiated and best in class CNI for the treatment of DES 36

37 VOS Clinical Development Strategy Phase IIa Randomized Active-Controlled Parallel-group study of the Ocular Tolerability of VOS in DES patients* Q week Primary & Secondary endpoints N = ~60 VOS.2% Restasis 2H.05% 2018 KEY INCLUSION CRITERIA Have a hx of DES in one or both eyes supported by a previous clinical diagnosis OUTCOME MEASURES Primary: Ocular tolerability vs. Restasis A symptom score of 30 on a VAS (1-100) Secondary: Adverse Events An anesthetized Schirmer score of 5 and 10/5min Secondary: OSDI, SANDE, VAS (dryness) Evidence of ocular surface staining (fluorescein staining of at least 3 (0-15)) Secondary: Corneal Staining, Conjunctival Staining, Schirmer test *Subject to FDA discussions 37

38 Investment Summary MANAGEMENT WITH TRACK RECORD OF SUCCESS & EXTENSIVE EXPERTISE IN LN SOLID LN CLINICAL DOSSIER Positive PoC and Phase IIB study results Positive interactions with regulatory authorities >2,400 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; Rolling NDA in preparation LARGE AND WELL-DEFINED MARKET OPPORTUNITIES >$2B Extremely high pharmaco-economic burden FSGS/MCD are synergistic disease areas, representing the same call points as LN; ability to add ~60K patients in U.S. STRONG CASH POSITION ~$182M as of September 30, 2017 LN patients appear to be readily assessable and easily identified by specialty treaters VOS presents unique partnering and/or divestiture opportunity 38

39 Milestones 1H H H H H H H 2021 Confirmatory DDI Study (LN) Initiate PhII FSGS/MCD Study AURORA Recruitment Complete AURORA Extension Study Begins FSGS/MCD Ph II Ongoing Data Readouts AURORA Phase 3 Data (LN) NS data readouts TARGET LN LAUNCH Initiate VOS Phase IIa DDI study FSGS/MCD Ongoing Data Readouts VOS Phase II data Submit IND for FSGS/MCD Rolling NDA (LN) Initiated: Non-Clinical Rolling NDA (LN):CMC NDA final submission (LN) Potential FDA Adcom (LN) FDA Meeting on VOS Potential approval (LN) 39

40 Thank You # Markham Street Victoria BC V8Z 7X8