AURORA Phase 3 Study Demonstrates Voclosporin Statistical - PowerPoint PPT Presentation

AURORA Phase 3 Study Demonstrates Voclosporin Statistical Superiority Over Standard of Care in Lupus Nephritis Keisha Gibson, MD, MPH, Samir Parikh, MD, Amit Saxena, MD, Neil Solomons, MD, Simrat Randhawa, MD, MBA for the AURORA Study Group 1

SLE & Lupus Nephritis (LN) Overview SLE is a chronic, complex and often CENTRAL NERVOUS disabling autoimmune disorder SYSTEM Headaches, dizziness, memory disturbances, Highly heterogeneous, Affects over 500K people in vision problems, seizures, affecting range of organ & stroke, the US (mostly women) 1 tissue systems 1 or changes in behavior HEART LN is an inflammation of the kidneys caused by SLE & Chest pains, represents a serious progression of SLE LUNGS heart murmurs Pleuritis, inflammation, or pneumonia Up to 50% of SLE patients develop LN 2 KIDNEYS Inflammation Leakage of blood proteins into the urine (proteinuria) is clinical sign of LN 4 BLOOD Straightforward disease outcomes—early response correlates Widespread w/long term outcomes; measured by proteinuria 2 Anemia, decreased white fatigue, fever, joint pain, cells, increased risk of muscle aches, blood clots photosensitivity, rashes, Debilitating and costly, often leading to hair loss, oral ulcers, ESRD, dialysis, renal transplant, and death 2 anxiety & depression Severe LN progresses to ESRD within 15 years of diagnosis in 10% to 30% of patients 3 1. Lupus Foundation of America website: http://www.lupus.org/about/statistics-on-lupus 2. NIDDK, Lupus Nephritis . https://www.niddk.nih.gov/health-information/health-topics/kidney- disease/lupus-nephritis/Pages/index.aspx. Accessed July 26, 2016. 3. Maroz N, Segal MS. Am J Med Sci . 2013;346(4):319-23. 4. https://www.lupus.org/resources/how-lupus-affects-the-renal-kidney-system . Abbreviations: SLE = systemic lupus erythematosus; ESRD = end stage renal disease 3

The Activity of Calcineurin Inhibitors (CNI) in Lupus Nephritis Involves Two Separate Mechanisms 1 2 Potential disease-modifying Inhibition of calcineurin podocyte stabilization, which reduced cytokine activation protects against proteinuria CNI CNI Actin cytoskeleton APC Cytoplasm T cell receptor Prevents the dephosphorylation of Calcineurin synaptopodin , which promotes the stabilization Nucleus of the podocyte actin IL-2 cytoskeleton Cell- INF-gamma mediated TNF-alpha immune response 4 Glomerular basement membrane Tissue damage Abbreviations: LN, lupus nephritis; NFAT, nuclear factor of activated T cells; APC, antigen-presenting cell; IL, interleukin; INF, interferon; TNF, tumor necrosis factor. 4

Voclosporin: A Novel CNI • Novel CNI developed as a structural change from cyclosporine A, incorporating a single carbon extension with a double-bond • Voclosporin has a consistent dose response potentially eliminating the need for therapeutic drug monitoring • 4x potency over cyclosporin A Source: Aurinia. Data on file. 5

Aurinia Studies Evaluating Voclosporin in Active Lupus Nephritis • Single arm, twin center exploratory study AURION • Biomarkers at 8 weeks: 25% reduction in UPCR. C3/C4, anti-dsDNA normalization (Proof of • N = 7 Concept) • Primary analysis: # patients achieving biomarkers and # of these patients who go on to achieve Week 24 or Week 48 remission • Phase 2 • Double blind RCT AURA-LV • N = 265 (Phase 2 RCT) • Active control • Primary endpoint: 24 week renal response • Phase 3 • AURORA Double blind RCT • N = 357 (Phase 3 RCT) • Active control • Primary endpoint: 52 week renal response Abbreviations: UPCR = urinary protein to creatinine ratio 6

The AURA-LV Phase 2 Study and the AURORA Phase 3 Study Have Similar Inclusion Criteria and Primary Endpoints • Bold = change from AURA-LV AURORA Select Inclusion Criteria Primary Endpoint Renal Response at Week 52 + + eGFR ≥60 mL/min/1.73m 2 or no confirmed decrease from baseline in eGFR of ≥20% + + + + * Up to 2 years if accompanied by laboratory evidence of recent LN flare ** Class V patients 7

AURORA Phase 3 Study Design Primary endpoint: Renal Response at 52-Weeks Primary endpoint Secondary endpoint 52 weeks 24 weeks VOCLOSPORIN 23.7 mg bid 1:1 Randomization 2-Year Extension MMF 2 g + oral corticosteroids N = 357 Study Treatment Arm PLACEBO MMF 2 g + oral corticosteroids Control Arm Rapid Steroid Taper 20-25 mg/daily 15-20 mg/daily 10-15 mg/daily 5 mg/daily 2.5 mg/daily 4 52 Week 2 6 16 24 8 Abbreviations: BID = twice a day 8

AURORA Subject Disposition Screened N = 758 Randomized N = 357 VCS 23.7 mg BID Placebo N = 179 N = 178 (100.0%) (100.0%) VCS 23.7 mg BID Placebo Treated Treated N = 178 N = 178 (99.4%) (100.0%) Completed Withdrawn Completed Withdrawn N = 147 N = 31 N = 162 N = 16 (82.6%) (17.4%) (90.5%) (8.9%) Abbreviations: VCS = voclosporin 9

AURORA Select Demographics and Baseline Characteristics (ITT) Control Voclosporin Total (N = 178) 23.7 mg BID (N = 179) (N = 357) Age (years) Mean (SD) 33.6 (11.0) 32.8 (10.93) 33.2 (10.96) 31.5 31.0 31.0 Median Sex n (%) Male 26 (14.6) 18 (10.1) 44 (12.3) Female 152 (85.4) 161 (89.9) 313 (87.7) Baseline weight (kg) Mean (SD) 66.55 (16.113) 66.49 (17.074) 66.52 (16.578) Median 63.50 64.60 64.10 Baseline UPCR (mg/mg) Mean (SD) 3.867 (2.3626) 4.138 (2.7109) 4.002 (2.5428) Median 3.128 3.356 3.216 Regional Distribution n (%) Asia Pacific 52 (29.2) 52 (29.1) 104 (29.1) Europe 51 (28.6) 46 (25.7) 97 (27.2) North/Latin America 74 (41.6) 75 (41.9) 149 (41.7) Abbreviations: ITT = intent to treat; SD = standard deviation 10

AURORA Baseline Renal Characteristics Control Voclosporin Total 23.7 mg BID N = 178 N = 179 N = 357 Baseline eGFR (mL/min/1.73m²) 178 178 356 n 90 + 29 92 + 31 91 + 30 Mean (SD) 97 91 94 Median Baseline UPCR (mg/mg) 178 178 356 n 3.9 + 2.4 4.1 + 2.7 4.0 + 2.5 Mean (SD) 3.1 3.4 3.2 Median Biopsy Class n (%) 178 179 357 153 (86%) 154 (86%) 307 (86%) Class III or IV (+/- V) 25 (14%) 25 (14%) 50 (14%) Class V 11

AURORA Primary Efficacy Endpoint: Week 52 Renal Response (ITT) p < 0.001 40.8% p 22.5% n = 178 n = 179 Control Voclosporin 23.7 mg BID 12

AURORA Secondary Endpoint: Week 24 Renal Response (ITT) p = 0.002 32.4% p 19.7% n = 178 n = 179 Control Voclosporin 23.7 mg BID 13

AURORA Secondary Endpoint: Partial Renal Response (ITT) Week 24 Week 52 p < 0.001 p < 0.001 70.4% 69.8% 51.7% 50.0% n = 178 n = 179 n = 178 n = 179 Control Voclosporin 23.7 mg BID Partial renal response = UPCR reduction > = 50% from baseline 14

AURORA Secondary Endpoint: Time to UPCR < 0.5 mg/mg 1.00 0.75 Probability of UPCR ≤ 0.5 mg/mg 0.50 0.25 + censored observation Logrank p < 0.0001 0.00 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 400 425 450 475 Time (days) Voclosporin Placebo Measure Result (Days) p-value Voclosporin:169 Median Time (50%) to UPCR < 0.5 mg/mg < 0.001 Control: 372 Voclosporin: 84 Median Time (25%) to UPCR < 0.5 mg/mg < 0.001 Control: 127 15

AURORA Hierarchical Secondary Endpoints (ITT) Odds Ratio Measure Result p-value [95% CI] Voclosporin 32.4% Renal Response at 24 weeks 2.23 [1.34, 3.72] 0.002 Control 19.7% Partial Renal Response at 24 Voclosporin 70.4% 2.43 [1.56, 3.79] < 0.001 weeks Control 50.0% Partial Renal Response at 52 Voclosporin 69.8% 2.26 [1.45, 3.51] < 0.001 weeks Control 51.7% Voclosporin faster than 2.02 [1.51, 2.70] Time to UPCR ≤ 0.5 mg/mg < 0.001 Control Hazard Ratio Voclosporin faster than 2.05 [1.62, 2.60] Time to 50% reduction in UPCR < 0.001 Control Hazard Ratio 16

AURORA Efficacy Benefit Seen Across Prespecified Subgroups Overall Age <=30 >30 Sex Female Male Race White Asian Other Biopsy Class Pure Class V Other Region Asia Pacific Europe + South Africa Latin America North America MMF at Screening Prior MMF Use No Yes Maximum MMF Dose <=2 mg g >2 mg g 0.1 0.2 0.3 0.4 0.5 0.6 0.8 1 2 3 4 5 6 7 8 9 11 13 15 18 21 25 OR and 95% CI for Voclosporin vs. Placebo 17 17

AURORA Corrected eGFR and Serum Creatinine Over Time 120 eGFR (mean) with SD 100 eGFR (mL/min/1.73m 2 ) p = ns 80 60 40 20 0 4 8 12 16 20 24 30 36 42 48 52 2 Weeks 2.3 Serum Creatinine (mean) with SD 1.8 1.3 mg/dL p = ns 0.8 0.3 -0.2 2 4 8 12 16 20 24 30 36 42 48 52 Weeks 18

AURORA: No Statistical Difference in Systolic BP or Diastolic BP 135 Systolic BP (Mean) Over Time with 95% CI 133 131 129 127 mmHg 125 123 p = ns 121 119 117 115 4 8 12 16 20 24 30 36 42 48 52 2 Weeks 90 Diastolic BP (Mean) Over Time with 95% CI 88 86 84 82 mmHg 80 p = ns 78 76 74 72 70 2 4 8 12 16 20 24 30 36 42 48 52 Weeks 19

AURORA Subjects Requiring Dose Adjustments Dose adjustments (interruption, reduction and re-escalation) were implemented according to eGFR reduction protocol after excluding potential contributing factors. AURORA 52 AURORA 52 Week Renal Week Renal Response In Patients with Response Dose Adjustment 60% 52.0% 50.0% 40.8% 40% 22.5% 20% n=178 n=179 n=31 n=16 n = 178 n = 179 n = 31 n = 16 0% n=178 n=179 n=16 n=31 Control Voclosporin 23.7 mg BID VCS Patients Dose VCS Patients Dose Control Adjusted and Adjusted and Maintained on 23.7 mg Maintained on 15.8 mg BID BID 20