Results of the 48-Week Blinded Extension of RADIANCE

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LB158 Results of the 48-Week Blinded Extension of RADIANCE: A Randomized, Placebo-controlled Phase 2 Trial of Oral Ozanimod in Relapsing Multiple Sclerosis JA Cohen1, K Selmaj2, DL Arnold3,4, G Comi5, A Bar-Or6, S Gujrathi7, JP Hartung7, A Olson7, M Cravets7, PA Frohna7 1Cleveland Clinic, Mellen Center for MS Treatment and Research, Cleveland, OH, USA, 2Medical University of Lodz, Department of Neurology, Lodz, Poland, 3NeuroRx Research, Montreal, QC, Canada, 4McGill University, Montreal, QC, Canada, 5San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Neurology, Milan, Italy, 6Montreal Neurological Institute, Department of Neurology and Neurosurgery, Montreal, QC, Canada, 7Receptos Services LLC., San Diego, CA, USA

Introduction Results

• Ozanimod (RPC1063) is a potent, orally-available modulator of Figure 2: Subject Disposition Safety Figure 4: Proportion of Patients Gd-Enhancing Lesion Free sphingosine1-phosphate (S1P) receptor 1 and 5 (S1P1R and S1P5R) under • The most common non-laboratory treatment-emergent adverse events development for relapsing multiple sclerosis (RMS) and inflammatory bowel Randomized (N=258) (TEAEs) were minor infections (nasopharyngitis, upper respiratory tract disease and urinary tract), back pain, and headache, which were similar across Placebo (N=88) Ozanimod 0.5 mg (N=87) Ozanimod 1 mg (N=83) dose groups • Ozanimod stimulation of S1P1R on lymphocytes results in receptor internalization and a functional antagonism that causes sequestration of • No notable cardiac, pulmonary, ophthalmologic, or malignancy TEAEs Discontinued 3 (3.4%) Discontinued 2 (2.3%) Discontinued 1 (1.2%) were observed lymphocytes in peripheral lymphoid organs and reduction in circulating Adverse event 0 Adverse event 0 Adverse event 0 lymphocytes Lost to follow-up 1 (1.1%) Lost to follow-up 0 Lost to follow-up 0 Protocol violation 0 Protocol violation 1 (1.1%) Protocol violation 0 Table 2: TEAEs During Blinded Extension • The therapeutic potential of S1P receptor modulation of this system has Consent withdrawn 2 (2.3%) Consent withdrawn 1 (1.1%) Consent withdrawn 1 (1.2%) been demonstrated with fingolimod (Gilenya® [Novartis]) , a non-selective Ozanimod 0.5 mg Ozanimod 1 mg Event N=126 N=123 S1P receptor agonist approved for RMS Completed 24-Week 85 Completed 24-Week 85 Completed 24-Week 82 PBO-Controlled (96.6%) PBO-Controlled (97.7%) PBO-Controlled (98.8%) ≥1 TEAE 86 (68.3%) 82 (66.7%) • RADIANCE is the first clinical trial of ozanimod in adults with RMS and is a Period Period Period of FreeGdE Lesion Proportion combined Phase 2/3 trial ≥1 moderate or severe TEAE 44 (34.9%) 38 (30.9%) Blinded 48- Blinded 48- Blinded 48-Week Extension Blinded 48-Week Extension Week Ext. Week Ext. Ozanimod 0.5 mg Ozanimod 1 mg ≥1 severe TEAE 5 (4.0%) 3 (2.4%) Objectives Ozanimod Ozanimod LDc HDc ≥1 related* TEAE 4 (3.2%) 2 (1.6%) 0.5 mg 1 mg (N=85) (N=81) • To evaluate the long-term efficacy and safety of low (LD, 0.5 mg) and high LDp HDp ≥1 serious TEAE 7 (5.6%) 5 (4.1%) (N=41) (N=42) (HD, 1 mg) dose ozanimod and efficacy of these doses in patients who Figure 5: Unadjusted Annualized Relapse Rate (uARR) ≥1 TEAE leading to withdrawal 3 (2.4%) 2 (1.6%) switch from placebo (PBO) in the blinded extension of the Phase 2 portion Completed Completed Completed 48-week Completed 48-week 48-week 48-week Extension Extension 0.6 *Assessed by the investigator as possibly related, probably related, or related. of RADIANCE Extension Extension Ozanimod 0.5 mg Ozanimod 1 mg Ozanimod Ozanimod (n=76) (n=78) Table 3: Incidence of Liver Transaminase Elevations During Methods 0.5 mg 1 mg (n=38) (n=38) Blinded Extension 0.4 Figure 1: Trial Design Ozanimod 0.5 mg Ozanimod 1 mg Table 1: Demographics and Disease Characteristics at Time of LDp LDc Total HDp HDc Total Parameter Criterion N=41 N=85 N=126 N=42 N=81 N=123 Entry Into Blinded Extension 0.2 ALT ≥3 × ULN 2 (4.9%) 1 (1.2%) 3 (2.4%) 3 (7.1%) 2 (2.5%) 5 (4.1%) Ozanimod Ozanimod Ozanimod Ozanimod 0.5 mg 0.5 mg 1 mg 1 mg AST ≥3 × ULN 1 (2.4%) 0 1 (0.8%) 1 (2.4%) 1 (1.2%) 2 (1.6%) (LDp) (LDc) (HDp) (HDc) ALT, alanine aminotransferase; AST, aspartate aminotransferase Characteristic N=41 N=85 N=42 N=81 Rates Relapse Annualized Unadjusted 0.0 Age (y) 41.0 (8.0) 38.0 (9.3) 36.9 (8.7) 38.5 (9.9) LDp (N=41) LDc (N=85) HDp (N=42) HDc (N=81) Cardiac Safety Wk 0-24 Wk 24-72 Wk 0-24 Wk 24-72 Wk 0-24 Wk 24-72 Wk 0-24 Wk 24-72 • Maximum first-dose reductions in mean hourly heart rate were < 1 bpm Male / female, % 27/73 32/68 29/71 30/70 Relapse is defined as the occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. from baseline White / Black / Asian, % 100/0/0 98/1/1 100/0/0 100/0/0 Table 4: Incidence of Minimum Heart Rates on Blinded Years since MS diagnosis 5.3 (5.2) 2.8 (5.0) 3.7 (5.1) 3.6 (4.5) Figure 6: Number of New or Enlarging T2 Lesions at Extension Day 1, Hours 1 to 6 EDSS score at Baseline 2.72 (1.2) 2.92 (1.3) 2.92 (1.4) 2.85 (1.2) Weeks 24 and 72 Ozanimod 0.5 mg Ozanimod 1 mg Minimum Relapses, last 12 months 1.3 (0.7) 1.4 (1.0) 1.4 (0.6) 1.3 (0.7) Heart Rate LDp LDc Total HDp HDc Total Relapses, last 24 months 2.0 (1.2) 2.0 (1.7) 1.7 (0.8) 1.8 (1.1) (bpm) N=41 N=85 N=126 N=42 N=81 N=123 GdE lesions at Baseline 1.8 (3.7) 0.9 (1.4) 0.6 (1.4) 1.4 (2.8) ≥65 12 (29.3%) 45 (52.9%) 57 (45.2%) 23 (54.8%) 48 (59.3%) 71 (57.7%) GdE lesion free at Baseline, n (%) 28 (68.3) 51 (60.0) 30 (71.4) 51 (63.0) 60 - 64 23 (56.1%) 24 (28.2%) 47 (37.3%) 13 (31.0%) 24 (29.6%) 37 (30.1%) Trial Population Data are mean (SD) unless indicated otherwise. 55 – 59 4 (9.8%) 12 (14.1%) 16 (12.7%) 4 (9.5%) 7 (8.6%) 11 (8.9%) • Key Inclusion Criteria 50 – 54 2 (4.9%) 4 (4.7%) 6 (4.8%) 1 (2.4%) 2 (2.5%) 3 (2.4%) − MS, as diagnosed by the revised 2010 McDonald criteria (Polman CH et

Mean (SE)Number of 45 – 49 000000 al. Ann Neurol. 2011;69:292-302) − Males and females aged 18-55 years Figure 3: Number of Gd-Enhancing Lesions 40 – 44 0 0 0 1 (2.4%)* 0 1 (0.8%) NewEnlarging or T2 Lesion Counts − Expanded Disability Status Scale (EDSS) score 0-5.0 < 40 000000 −≥1 relapse within the last 12 months OR ≥1 relapse within the last 24 7 *Pre-dose HR=55 bpm, Hr 4 post-dose HR=44 bpm, Hr 5 HR=60 bpm. No signs/symptoms; not an AE since patient had resting HR=49 bpm one day earlier while taking Placebo. months and ≥1 gadolinium-enhancing (GdE) lesion on brain MRI within the last 12 months 6 Figure 7: Proportion of Subjects With No Evidence of Disease Conclusions • Key Exclusion Criteria Activity (NEDA) at Weeks 24 and 72 • Both doses of ozanimod demonstrated efficacy over 72 weeks on MRI and − Primary progressive MS at screening 5 clinical measures of MS disease activity in patients continuing ozanimod and − Prior treatment with lymphocyte-trafficking blockers (e.g., natalizumab, those switching from PBO at Wk 24 fingolimod, other S1P receptor agonists) or lymphocyte-depleting 4 • No new safety or tolerability issues were identified in the 48-week blinded therapies (e.g., rituximab) extension − Treatment with other disease modifying therapies within 3 months prior 3 • Overall, the results of the RADIANCE Phase 2 core study and extension to randomization (e.g., dimethyl fumarate, teriflunomide, daclizumab, or support a favorable risk-benefit profile for ozanimod laquinimod) • These results support the ongoing Phase 3 RADIANCE and SUNBEAM trials

Mean (SE) Number of 2

− Treatment with other immunosuppressant agents within 6 months prior Lesions Gd-Enhancing to randomization (e.g., azathioprine, cyclosporine, methotrexate, or Free Activity Disease Disclosures Proportion who of Patients are Proportion mycophenolate) 1 J.A. Cohen: EMD Serono, Genentech, Innate Immunotherapeutics, Receptos, Vaccinex. K. Selmaj: Genzyme, Novartis, − Systemic corticosteroid or ACTH use within 30 days prior to screening Ono, Roche, Synthon, Teva, Biogen Idec, Merck, Receptos. D.L. Arnold: Acorda, Bayer, Biogen Idec, Eli Lilly, Serono, Genentech,, Genzyme, GSK, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi-Aventis, Teva, the Non-lymphocyte-depleting disease-modifying MS agents (e.g., glatiramer 0 Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada. G. Comi: Almirall, Bayer, Chugai, Excemed, LDp LDc HDp HDc Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva, Almirall, Bayer. A. acetate, interferons) were to be discontinued from signing of informed consent NEDA: No evidence of disease Bar-Or: Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec,, BioMS, Diogenix, Eli-Lilly, EMD Serono, Wk 24 Wk 72 Wk 24 Wk 72 Wk 24 Wk 72 Wk 24 Wk 72 • 24 Week: No GdE or new/enlarging T2 lesions at Week 24 and no relapse or increase in EDSS from Baseline to Week 24 Genentech, Genzyme, GlaxoSmithKline, Guthy-Jackson/GGF, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, This study was conducted at 55 sites in the United States, Belgium, Bulgaria, Georgia, Greece, n=41 n=38 n=85 n=75 n=42 n=36 n=81 n=78 • 72 Week: No GdE or new/enlarging T2 lesions at Week 72 and no relapse or increase in EDSS from Week 24 to Week 72 Receptos, Roche, Sanofi Aventis, Teva, Wyeth. Amplimmune, EMD Serono, Novartis. J.P. Hartung, A. Olson, M. Cravets, PA Frohna are Receptos Hungary, Italy, Poland, Romania, Russia, Serbia, Spain, Ukraine. employees. S. Gujrathi previously was an employee of Receptos.