Well-Established Safety Profile^1-4a

Overall ZEPOSIA exposure in parent and extension trials (phase 1-3 MS, phase 2-3 UC) was 18,255.07 patient years (PY) and estimated to be 64,039 PY in the post-marketing setting. The cumulative number of patients exposed to ozanimod in parent and extension trials (all indications) was 4154 and estimated to be 68,146 in the post-marketing setting. Clinical trial data is current as of May 19, 2025, and post-marketing estimated data is current as of May 19, 2025.^1,5-14

^aZEPOSIA has been studied across multiple indications in 4 clinical trials, including TRUE NORTH (Ph 3); TOUCHSTONE (Ph 2); and SUNBEAM (Ph 3) and RADIANCE (Ph 3). 496 patients receiving the 0.92 mg oral once daily dose of ZEPOSIA during induction in TRUE NORTH or TOUCHSTONE and 882 patients receiving the 0.92 mg oral once daily dose of ZEPOSIA in SUNBEAM or RADIANCE were assessed in the safety analysis.^1,5-7,9,10

^bIn UC, from the start of the TOUCHSTONE Phase 2 clinical trial (December 26, 2012) through TRUE NORTH OLE study data cutoff (June 30, 2023). In MS, from the start of the RADIANCE Phase 2 clinical trial (September 18, 2012) through the DAYBREAK OLE database lock (April 7, 2023). Only includes patients receiving the 0.92 mg oral daily dose of ZEPOSIA.^1,4,5,8,17

Moderate-to-severe UC: TRUE NORTH (NCT02435992), a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial; TRUE NORTH OLE (NCT02531126), an ongoing Phase 3, multicenter, OLE trial; TOUCHSTONE (NCT01647516), a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial; JAPAN TRUE NORTH (NCT03915769), a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled, treat-through study. ^5,9-11,13

Relapsing MS: SUNBEAM (NCT02294058) and RADIANCE (NCT02047734), 2 Phase 3, multicenter, randomized, double-blind, double-dummy, active treatment-controlled studies; DAYBREAK (NCT02576717), a Phase 3, multicenter, OLE trial; ENLIGHTEN (NCT04140305), an ongoing Phase 3b, multicenter, longitudinal, open-label, single arm study.^{1,4,6,7,12,14}

MS=multiple sclerosis; OLE=open-label extension; Ph=phase; UC=ulcerative colitis.

Safety Comparable to Avonex in Overall Incidence of AEs, and Generally Similar Safety in Long-Term Extension Study;
10 Years* of Experience^1,15-17

In Pivotal Trials: Incidence of Adverse Reactions^1-3

Adverse reactions are sorted by decreasing incidence in patients treated with ZEPOSIA. For adverse reactions pertaining to liver function tests, increases were transient and generally resolved without discontinuation.
Elevations of 3-fold the ULN or greater occurred in 5.5% of patients taking ZEPOSIA and in 3.1% of patients taking Avonex. The majority (79%) continued treatment with ZEPOSIA with values returning to less than 3 times the ULN within approximately 2 to 4 weeks.^1-3

*From the first patient randomized (October 18, 2012) through the DAYBREAK database lock (April 7, 2023), the maximum exposure was 117.2 months. The mean duration of any ZEPOSA 0.92 mg oral daily dose exposure in the parent trials and DAYBREAK was 74.8 months.^4
aData are not an adequate basis for comparison of rates between ZEPOSIA and the active control.^4
bIncludes the following terms: nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, rhinitis, respiratory tract infection viral, viral upper respiratory tract infection, rhinorrhea, tracheitis, and laryngitis.^4
cIncludes the following terms: alanine aminotransferase increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, hepatic enzyme increased, liver function test abnormal, and transaminases increased.4
^dIncludes hypertension, essential hypertension, and orthostatic hypertension.⁴

AE=adverse event; ULN=upper limit of normal.

DAYBREAK OLE: Incidence of Adverse Events⁴

^eALC reductions are an expected pharmacodynamic effect related to the mechanism of ozanimod; although investigators were not required to report ALC reductions as TEAEs, lymphopenia and ALC decreases were reported as TEAEs according to investigator determination.^4
fIncludes preferred terms of hypertension, essential hypertension, labile hypertension, and systolic hypertension.^4
gIncludes preferred terms of depression, depressed mood, and depressive symptoms.⁴

ALC=absolute lymphocyte count; ALT=alanine aminotransferase; GGT=gamma-glutamyl transferase; TEAE=treatment emergent adverse event.

Demonstrated Tolerability Profile With Low Discontinuation Rates Due to Adverse Events^2-4

Rates of Serious Infections and Malignancies Consistent vs Avonex

The rate of serious infections at 1 year for ZEPOSIA was 1.1% vs 0.7% for Avonex, and the rate at 2 years for ZEPOSIA
was 0.9% vs 0.9% for Avonex. The rate of malignancies at 1 year for ZEPOSIA was 0.2% vs 0% for Avonex, and the rate at 2 years for ZEPOSIA was 0.9% vs 0.5% for Avonex.^1-4

► Overall Infections

In SUNBEAM and RADIANCE, the overall rate of infections with ZEPOSIA (35%) was similar to Avonex (34%). ZEPOSIA causes a reduction in peripheral blood lymphocyte count and may increase the risk of infection.¹

Herpetic Infections

In active-controlled MS trials, herpes zoster was reported as an adverse reaction in 0.6% of patients treated with once-daily oral ZEPOSIA 0.92 mg and in 0.2% of patients taking Avonex.¹