Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

This is a Phase 2b, multicenter, multinational, randomized, double-blind, placebo-controlled
study to evaluate the efficacy and safety of 4 doses of cenerimod versus placebo in adult
subjects with moderately to severely active, autoantibody-positive systemic lupus
erythematosus (SLE).

Approximately 500 adult subjects with SLE will be randomized in a 1:1:1:1:1 ratio to placebo,
0.5, 1, 2, or 4 mg o.d. of cenerimod, in addition to background SLE therapy.

Inclusion Criteria:

- Signed ICF prior to any study-mandated procedure

- Diagnosis of SLE made at least 6 months prior to Screening, by fulfilling at least 4
of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR)
criteria

- A mSLEDAI-2K score ≥ 6 of at least 2 points for musculoskeletal or mucocutaneous
manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).

- Currently treated with stable doses of one or more of the following background
medications:

- NSAIDs

- Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100
mg/day quinacrine)

- Mycophenolate mofetil (≤ 2 g/day)

- Azathioprine (≤ 2 mg/kg/day)

- Methotrexate (≤ 20 mg/week)

- Corticosteroids (≤ 40 mg/day prednisone or equivalent)

- Belimumab (≤10 mg/kg every 4 weeks)

- History or presence of positive autoantibodies measured by central laboratory defined
as follows: (a) Positive antinuclear antibody (ANA) test measured by
immunofluorescence assay (IFA) with titre ≥1:80; AND/OR (b) positive anti-double
stranded deoxyribonucleic acid (antidsDNA) antibodies with titre ≥30 IU/mL

- Women of childbearing potential:

- Must have a negative serum pregnancy test at Screening

- Must agree to undertake monthly urine pregnancy tests during the study

- Must use highly effective methods of contraception from the screening visit until
4 months after taking the last dose of study treatment

Exclusion Criteria:

- Active lupus nephritis or a renal biopsy demonstrating immune complex mediated
glomerulonephritis compatible with lupus nephritis.

- CNS lupus and severe forms of vasculitis requiring systemic immunosuppressive
treatment

- A diagnosis of mixed connective tissue disease or any history of overlap syndromes of
SLE with rheumatoid arthritis, erosive arthritis, scleroderma or autoimmune hepatitis

- History or presence of Mobitz type II or third-degree atrioventricular block, sick
sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders

- Subjects who experienced myocardial infarction, unstable angina pectoris, stroke,
transient ischemic attack, vascular thrombosis, decompensated heart failure requiring
hospitalization, or heart failure defined by the New York Heart Association Class
III/IV within six months prior to Screening

- An elevated QT corrected for HR on the basis of Fridericia's formula interval of > 470
ms (females) / > 450 ms (males)

- History or presence of severe respiratory disease or pulmonary fibrosis

- Active or latent tuberculosis

- Ongoing bacterial, viral or fungal infection that is of clinical concern in the
judgment of the investigator or history of any serious infection

- Subjects who have congenital or acquired severe immunodeficiency or known HIV
infection or positive HIV testing

- Presence of macular edema or active uveitis

- Type 1 or 2 diabetes that is poorly controlled according to investigator judgment, or
diabetes complicated with organ involvement such as diabetic nephropathy or
retinopathy

- Significant hematology abnormality: Lymphocyte count < 800 /μL (0.8 × 10e9/L);
hemoglobin < 9 g/dL; WBC count < 2500/μL (2.5 × 10e9/L) or platelets < 75000/μL (75 ×
10e9/L)

- Estimated glomerular filtration rate < 60 mL/min/1.73 m2

- Known allergy to S1P receptor modulators or any of the cenerimod formulation
excipients