cenerimod (ACT-334441) / Idorsia, Viatris, Nxera Pharma - LARVOL DELTA

A Study to Evaluate the Safety,Tolerability,Pharmacokinetics and Pharmacodynamics of Cenerimod in Adult Chinese Participants With Moderate-to-severe Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Viatris Pharmaceuticals Co., Ltd.

New P2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Post-hoc Analysis of Sustained Response Over Time in Systemic Lupus Erythematosus Patients Treated with Cenerimod in CARE (Phase 2 B) Study (ACR Convergence 2025) - P2, P3 | "This analysis showed that over a period of 12 months, patients in the cenerimod Ex-4 mg group were 1.43 times more likely to achieve a 4-month sustained response than those receiving placebo.The ongoing confirmatory Phase 3 program OPUS (NCT05648500 and NCT05672576) will further evaluate the safety and efficacy of 4 mg cenerimod in adults with SLE."

Clinical • P2b data • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Effect of Cenerimod on Four Main Clinical Items of SLEDAI-2K Score in SLE Patients in a Phase 2b Study (ACR Convergence 2025) - P2, P3 | "This post-hoc analysis provided insights to the trends in improvements of four individual SLEDAI-2K clinical components when patients were treated with cenerimod 4 mg dose for 6 months. There was no obvious difference in arthritis or rash scores vs placebo. However, as compared to placebo, better early improvement was seen in alopecia (from month 4) and mucosal ulcers (from month 4) until month 6."

Clinical • P2b data • Alopecia • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus

CARE: Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=427 | Completed | Sponsor: Viatris Innovation GmbH | Phase classification: P2b ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Research Trial to Assess if Cenerimod is Efficacious and Safe to Treat Active Lupus Nephritis on Top of Regular Treatment (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Viatris Innovation GmbH

New P3 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

REGISTRY OF ANIFROLUMAB USE IN SYSTEMIC LUPUS ERYTHEMATOSUS IN THE VALENCIAN COMMUNITY (EULAR 2025) - "Only 1 patient was treated with anifrolumab without prior disease-modifying antirheumatic drugs (DMARDs) therapy, with an average of 2.6±1.25 previous DMARDs (23 hydroxychloroquine, 13 MTX, 15 azathioprine, 10 mycophenolate, 5 tacrolimus, 5 leflunomide, 1 cyclosporine, 1 chloroquine, 1 dapsone). The mean number of prior biologics before starting Anifrolumab was 1.29±0.78 (15 belimumab, 13 rituximab, 1 tocilizumab, 1 abatacept, 2 antiTNF, 1 cenerimod). Only 33.33% required corticosteroid boluses, and one required cyclophosphamide. Anifrolumab was concomitantly prescribed with hydroxychloroquine in 53.33% of patients, mycophenolate in 13.33%, methotrexate in 20% and azathioprine, tacrolimus and mepacrine in 6.66%... From the third month of Anifrolumab treatment, a significant reduction in prednisone dose mantained until 6th month, as well as SLEDAI scores, were observed. The domains showing the greatest improvement were hematological, joint, and mucocutaneous,..."

Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Post-hoc analysis of sustained response over time in Systemic lupus erythematosus patients treated with Cenerimod in CARE (Phase 2 b) study (EULAR 2025) - P2b, P3 | "This analysis showed that over a period of 12 months, patients in the cenerimod Ex-4 mg group were 1.43 times more likely to achieve a 4-month sustained response than those receiving placebo. The ongoing confirmatory Phase 3 program OPUS (NCT05648500 and NCT05672576) will further evaluate the safety and efficacy of 4 mg cenerimod in adults with SLE."

Clinical • P2b data • Retrospective data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Leukopenia • Lupus • Multiple Sclerosis • Systemic Lupus Erythematosus • Ulcerative Colitis

Idorsia reaches an agreement with significant bondholders to restructure its convertible bond debt and to secure funding for future operations (Idorsia Press Release) - "Agreement with Viatris to revise collaboration for selatogrel and cenerimod results in the removal of significant cash requirement for 2025...In a third step of the restructuring, a special purpose vehicle (SPV) will be created. Idorsia intends to transfer to this SPV its rights to selatogrel and cenerimod, and its rights to aprocitentan. A bond exchange offer will be launched by the SPV, where the CB2025 and CB2028 bondholders will be offered the opportunity to exchange their convertible bonds for newly created notes issued by the SPV (SPV Notes)....Any potential net payments for milestones and royalties from selatogrel and cenerimod, as well as any potential net proceeds from a deal for aprocitentan will be used to repay holders of the SPV Notes."

Commercial • Cardiovascular • Lupus

Nxera Pharma Assigns Japan and APAC (ex-China) Rights to Cenerimod for Autoimmune Diseases to Viatris (GlobeNewswire) - "Nxera Pharma...has entered an assignment agreement with Viatris...and Idorsia Pharmaceuticals Ltd...regarding the development and commercialization of cenerimod, a clinical-stage immunology candidate for autoimmune diseases, in Japan, South Korea, and certain countries in the Asia-Pacific (APAC) region (excluding China). The agreement was signed concurrently with Nxera’s assignment of its option to these same rights from Idorsia Pharmaceuticals Ltd under its agreement in July 2023 to acquire Idorsia Pharmaceuticals Japan Ltd and Idorsia Pharmaceuticals Korea Co., Ltd. Nxera will receive an upfront payment of US$10 million from Viatris and is eligible to receive a milestone payment upon regulatory approval of cenerimod in Japan plus royalties on net sales should it be commercialized in the assigned territories."

Licensing / partnership • Systemic Lupus Erythematosus

OPUS OLE: Long-term Safety and Tolerability of Cenerimod in Adults With Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=680 | Enrolling by invitation | Sponsor: Idorsia Pharmaceuticals Ltd. | Trial primary completion date: Nov 2027 ➔ May 2028

Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Pharmacodynamics of the S1P1 receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE. (PubMed, Ann Rheum Dis) - P2b | "This study further characterised the mechanism of action of cenerimod in patients with SLE and substantiated the scientific rationale for cenerimod 4 mg in the phase 3 clinical trials in moderate to severe SLE (OPUS-1/-2)."

Biomarker • Clinical • Journal • P2b data • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IFNG

Viatris Announces Publication of Phase 2b CARE Study Data for Cenerimod in Lancet Rheumatology (PRNewswire) - P2b | N=427 | CARE (NCT03742037) | Sponsor: Idorsia Pharmaceuticals Ltd. | "Viatris Inc...announced the publication of Phase 2b CARE study results evaluating the efficacy and safety of cenerimod in adults with moderate-to-severe systemic lupus erythematosus (SLE)....At month 6, the maximum response was observed within the 4 mg group with least squares mean change from baseline in mSLEDAI-2K score being -4.04 (95% CI -4.79 to -3.28; difference vs placebo -1.19 [-2.25 to -0.12]; p=0.029). Furthermore, in a subgroup analysis, patients with a high IFN-1 gene expression signature treated with cenerimod 4 mg showed greater reduction in mSLEDAI-2K at month 6 at -2.78 as compared to placebo. Also, 24% higher SRI-4 response rate was seen as compared to placebo in this subgroup."

P2b data • Immunology • Lupus • Systemic Lupus Erythematosus

Cenerimod, a sphingosine-1-phosphate receptor modulator, versus placebo in patients with moderate-to-severe systemic lupus erythematosus (CARE): an international, double-blind, randomised, placebo-controlled, phase 2 trial. (PubMed, Lancet Rheumatol) - P2b, P3 | "The primary endpoint was not met. Cenerimod was well tolerated over 12 months. Cenerimod 4·0 mg is being investigated for the treatment of SLE in two ongoing phase 3 trials (NCT05648500, NCT05672576)."

Journal • P2 data • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Leukopenia • Lupus • Systemic Lupus Erythematosus

Pharmacodynamics of the S1P1 receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE. (PubMed, Ann Rheum Dis) - P2b | "This study further characterised the mechanism of action of cenerimod in patients with SLE and substantiated the scientific rationale for cenerimod 4 mg in the phase 3 clinical trials in moderate to severe SLE (OPUS-1/-2)."

Journal • P2b data • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IFNG

The contribution of the sphingosine 1-phosphate signaling pathway to chronic kidney diseases: recent findings and new perspectives. (PubMed, Pflugers Arch) - "Emerging studies underscore the therapeutic potential of modulating S1P signaling with receptor modulators and inhibitors, such as fingolimod (FTY720) and more selective agents like ozanimod and cenerimod. Advanced technologies, including spatial transcriptomics, are further refining our understanding of S1P's role within specific kidney compartments. Collectively, these insights emphasize the need for continued research into S1P signaling pathways as promising targets for CKD treatment strategies."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fabry Disease • Fibrosis • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease

A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of a Single Dose of Cenerimod (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Idorsia Pharmaceuticals Ltd. | Recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2024 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatology

OPUS OLE: Long-term Safety and Tolerability of Cenerimod in Adults With Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=680 | Enrolling by invitation | Sponsor: Idorsia Pharmaceuticals Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Viatris Presents Late Breaking Abstract on Cenerimod at the 26th Asia-Pacific League of Associations for Rheumatology Annual Congress (PRNewswire) - P2 | N=427 | NCT03742037 | Sponsor: Idorsia Pharmaceuticals Ltd. | "Viatris Inc...presented today the results of one of its Phase 2 studies of cenerimod (ACT-333441). The ACT-333441 study was accepted as a late-breaking abstract and was presented during an oral presentation at the 26th Asia-Pacific League of Associations for Rheumatology (APLAR) Annual Congress. The congress is being held August 21-25, 2024, in Suntec, Singapore....Both cenerimod doses were considered safe and well-tolerated. A decrease in lymphocyte counts was observed in both the 2 mg and 4 mg doses as expected per the mechanism of action of cenerimod and was reversible upon treatment discontinuation. Both doses showed a clinically meaningful improvement in disease activity, as measured by mSLEDAI-2K, which persisted long after the treatment was discontinued and was higher with the 4 mg dose."

P2 data • Immunology • Systemic Lupus Erythematosus

Multiple-dose pharmacokinetics of cenerimod and the effect of charcoal on its elimination. (PubMed, J Clin Pharmacol) - "A reversible, dose-dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated."

Journal • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • S1PR1

Cenerimod in Japanese patients with moderate to severe systemic lupus erythematosus (SLE): A Phase 2, randomized, double-blind trial (APLAR 2024) - No abstract available

Clinical • Late-breaking abstract • P2 data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

OPUS OLE: Long-term Safety and Tolerability of Cenerimod in Adults With Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=680 | Not yet recruiting | Sponsor: Idorsia Pharmaceuticals Ltd.

New P3 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

TARGETING KEY COMPONENTS OF SLE PATHOGENESIS WITH THE MULTIFACETED IMMUNOMODULATORY PROPERTIES OF CENERIMOD, A SELECTIVE S1P1 RECEPTOR MODULATOR (EULAR 2024) - P1/2, P2b, P3 | "Both preclinical and clinical research provide evidence that cenerimod is a promising immunomodulatory drug candidate that addresses three critical aspects of SLE pathogenesis: migration of autoreactive lymphocytes, release of pro-inflammatory cytokines and chemokines, and continuous autoimmune priming. The S1P 1 receptor modulator cenerimod may effectively interrupt this pathogenic circle of SLE autoimmunity. The ongoing OPUS Phase 3 program (NCT05648500, NCT05672576) is designed to further investigate the safety and efficacy of cenerimod at a dose of 4 mg for the treatment of SLE in adults."

Immunomodulating • Inflammatory Arthritis • Lupus • IFNA1

PHARMACODYNAMIC EFFECTS OF THE SELECTIVE S1P1 RECEPTOR MODULATOR CENERIMOD ON THE BLOOD TRANSCRIPTOME OF PATIENTS WITH SLE (EULAR 2024) - P2b, P3 | "These results confirm the S1P 1 -dependent immunomodulatory properties of cenerimod and demonstrate that only 4 mg consistently reduced the investigated disease-relevant pathways. The efficacy and safety of 4 mg cenerimod is under evaluation in two Phase 3 clinical studies for SLE (OPUS – NCT05648500, NCT05672576)."

Clinical • PK/PD data • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD4 • CD8 • IFNG

A Research Study to Evaluate the Effects of a New Oral Medicine Called Cenerimod in Adults With Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Idorsia Pharmaceuticals Ltd. | Trial completion date: Jun 2026 ➔ May 2027 | Trial primary completion date: Dec 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

OPUS-2: A Research Study to Evaluate the Efficacy and Safety of Cenerimod in Subjects Suffering From Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Idorsia Pharmaceuticals Ltd. | Trial completion date: Jul 2026 ➔ May 2027 | Trial primary completion date: Jan 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus