enpatoran (M5049) / EMD Serono - LARVOL DELTA

A Long-Term Extension (LTE) Study Of Enpatoran In Cutaneous Manifestations Of Lupus With Or Without Systemic Disease [Elowen-LTE] (clinicaltrials.gov) - P3 | N=404 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

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

Safety and Efficacy of Enpatoran in Lupus: Results Up To 109 Weeks of the Phase II WILLOW Long-Term Extension Study (ACR Convergence 2026) - No abstract available

Clinical • P2 data • Immunology • Inflammatory Arthritis • Lupus

Efficacy of enpatoran on arthritis outcomes in participants with SLE and active skin and joint involvement: a post-hoc analysis of Cohort B of the phase II WILLOW study (ACR Convergence 2026) - No abstract available

Clinical • P2 data • Retrospective data • Immunology • Inflammatory Arthritis • Rheumatology

Improvement in Active Cutaneous Manifestations of Lupus with Enpatoran in Participants with Cutaneous Lupus Erythematosus or Systemic Lupus Erythematosus: A Pooled Post-Hoc Exploratory Analysis of the Phase 2 Willow Study (EADV 2026) - No abstract available

P2 data • Retrospective data • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Enpatoran, a Toll-Like Receptor 7/8 Inhibitor, in Skin Manifestations of Cutaneous Lupus Erythematosus or Systemic Lupus Erythematosus: Pooled Safety Data from the Phase 2 WILLOW Trial (EADV 2026) - No abstract available

Clinical • P2 data • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

Design of Phase 3, Randomised, Double-Blind, Placebo-Controlled Parallel Studies to Evaluate the Efficacy and Safety of Enpatoran in Active Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-1 and ELOWEN-2) (EADV 2026) - No abstract available

Clinical • P3 data • Immunology • Inflammatory Arthritis • Lupus

Improvement in CLA-IGA(-R) outcomes with enpatoran in participants with active cutaneous manifestations of lupus with or without systemic disease: post-hoc analysis of the phase II WILLOW study (EADV 2026) - No abstract available

P2 data • Retrospective data • Immunology • Inflammatory Arthritis • Lupus

Study of M5049 in DM and PM Participants (NEPTUNIA) (clinicaltrials.gov) - P2 | N=20 | Terminated | Sponsor: EMD Serono Research & Development Institute, Inc. | N=40 ➔ 20

Enrollment change • Dermatomyositis • Immunology • Myositis

Microglial TLR7 contributes to traumatic brain injury-induced neuroinflammation in mice. (PubMed, Acta Pharmacol Sin) - "Additionally, M5049 was not able to rescue glutamate- and H2O2-induced cell death in HT22 mouse hippocampus neuronal cells, or broadly suppress the examined peripheral immune transcriptional program. These findings identify microglial TLR7 as an important player in TBI-induced neuroinflammation and support a predominantly TLR7-dependent anti-inflammatory effect of M5049."

IO biomarker • Journal • Preclinical • CNS Disorders • Inflammation • Vascular Neurology • CD86 • IL1B • IL6 • LGMN • TLR7 • TLR8 • TNFA

Modern Therapies for Discoid Lupus Erythematosus: A Narrative Review. (PubMed, Dermatol Ther (Heidelb)) - "Ongoing advances in understanding the immune mechanisms underlying DLE are shaping a transition from broad immunosuppression toward more targeted treatment strategies. Integrating newer biologic and small-molecule therapies with conventional management may offer improved control and better long-term outcomes for patients with chronic disease."

Journal • Review • Alopecia • Cutaneous Lupus Erythematosus • Discoid Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • TYK2

TLR7 Inhibition Limits Ischemic Cardiac Injury by Disrupting ITGAM-Dependent Immune-Endothelial Interactions. (PubMed, JACC Basic Transl Sci) - "Genetic deletion or pharmacologic inhibition of TLR7 with enpatoran reduced inflammation and myocardial infarction (MI) size and improved cardiac function 24 hours after I/R in mice...TLR7/8 activation promoted ITGAM-dependent endothelial-leukocyte interactions under shear stress, whereas ITGAM blockade reduced immune cell infiltration and limited MI injury. These findings identify the TLR7-ITGAM signaling axis as a central driver of endothelial-leukocyte crosstalk in myocardial I/R injury and support TLR7 inhibition as a promising therapeutic strategy to mitigate ischemic MI after percutaneous coronary intervention."

IO biomarker • Journal • Cardiovascular • Inflammation • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury • ITGAM • TLR7

EMD Serono Announces FDA Breakthrough Therapy Designation for Enpatoran in Lupus Patients with Active Skin Manifestations (Businesswire) - "The FDA Breakthrough Therapy designation is supported by results from the Phase 2 WILLOW study..."

Breakthrough therapy • Cutaneous Lupus Erythematosus • Lupus • Systemic Lupus Erythematosus

Improvement in active cutaneous manifestations of lupus with enpatoran in participants with cutaneous lupus erythematosus or systemic lupus erythematosus: A pooled post-hoc exploratory analysis of the phase II WILLOW study (EULAR 2026) - P2 | "Conclusions Enpatoran provided clinically meaningful improvements in cutaneous disease activity in participants with CLE and SLE, underscoring shared pathogenic mechanisms. Phase III evaluation of enpatoran in cutaneous manifestations of lupus with or without systemic disease activity is planned."

IO biomarker • P2 data • Retrospective data • Cutaneous Lupus Erythematosus • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

Dose selection of enpatoran for phase III trials in lupus erythematosus with active cutaneous manifestations: pharmacometric analyses of phase II dose-ranging WILLOW study data (EULAR 2026) - "Conclusions This model-informed approach leveraging the totality of available data enhances the understanding of the dose-exposure-response relationship, supporting the selection of 50 mg enpatoran BID as the phase III dose. By effectively balancing patient benefits with safety considerations, this dose has achieved regulatory acceptance as the sole dose for investigation in the phase III programme."

IO biomarker • P2 data • P3 data • Cutaneous Lupus Erythematosus • Herpes Zoster • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Varicella Zoster • TLR7

Design of a Phase 3, Randomised, Double-Blind, Placebo-Controlled Parallel Study to Evaluate the Efficacy and Safety of Enpatoran in Cutaneous Manifestations of Lupus With or Without Systemic Disease (EULAR 2026) - P2 | "Conclusions This novel phase 3 trial design aims to benefit a broader group of participants than conventional CLE or SLE trials, by evaluating enpatoran in participants with cutaneous manifestations of lupus with or without systemic disease. This approach has the potential to transform the lupus treatment paradigm for cutaneous manifestations of the disease, whilst also addressing underlying lupus pathophysiology upstream of IFN."

Clinical • IO biomarker • P3 data • Cutaneous Lupus Erythematosus • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

Safety and efficacy of enpatoran in lupus: Results from the first 48 weeks of the phase II WILLOW long-term extension study (EULAR 2026) - P2 | "Enpatoran continued to provide clinically meaningful improvement in cutaneous disease activity, including high rates of CLASI-70 responses, in participants with active cutaneous manifestations. Further evaluation of the efficacy and safety of enpatoran in patients with active cutaneous manifestations of lupus with/without systemic disease activity is planned."

Clinical • IO biomarker • P2 data • Cervical Cancer • Cutaneous Lupus Erythematosus • Gynecology • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Nephrology • Respiratory Diseases • Systemic Lupus Erythematosus • TLR7

Efficacy of enpatoran on arthritis outcomes in participants with active cutaneous manifestations of SLE: A post-hoc analysis of Cohort B of the phase II WILLOW study (EULAR 2026) - P2 | "Conclusions Enpatoran improved arthritis outcomes compared with placebo in participants with moderate-to-severe SLE and active cutaneous manifestations at baseline. Further investigation of enpatoran in cutaneous manifestations of lupus, with or without systemic disease activity, is planned."

Clinical • P2 data • Retrospective data • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Musculoskeletal Diseases • Rheumatology • Systemic Lupus Erythematosus • TLR7

Could enpatoran add to our therapeutic toolbox in SLE? (PubMed, Lancet) - No abstract available

Journal • Inflammatory Arthritis

Efficacy and safety of enpatoran, a Toll-like receptor 7/8 inhibitor, in patients with skin manifestations of cutaneous lupus erythematosus or systemic lupus erythematosus: findings from Cohort A of a multicentre, international, double-blind, placebo-controlled, dose-finding phase 2 trial. (PubMed, Lancet Rheumatol) - P2 | "Enpatoran showed a significant and dose-dependent effect on disease activity in participants with active cutaneous manifestations of CLE or SLE, and was well tolerated."

Journal • P2 data • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Respiratory Diseases • Systemic Lupus Erythematosus • TLR7 • TLR8

Enpatoran, a Toll-like receptor 7/8 inhibitor, in moderate-to-severe systemic lupus erythematosus: findings from Cohort B of a multicentre, international, double-blind, placebo-controlled dose-finding phase 2 trial. (PubMed, Lancet) - P2 | "In this study of participants with moderate-to-severe SLE, enpatoran improved BICLA response rates versus placebo; however, the primary objective of a statistically significant dose-dependent effect on disease activity based on BICLA response was not met. Enpatoran was well tolerated across all dose groups."

Clinical • IO biomarker • Journal • P2 data • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

Enpatoran: promising mechanism, pharmacodynamic challenge. (PubMed, Lancet Rheumatol) - No abstract available

Journal • PK/PD data

Merck…announced the first patient was dosed in the Phase 3 program, ELOWEN-1 (NCT07332481) and ELOWEN-2 (NCT07355218), evaluating enpatoran in people living with lupus who experience active skin manifestations. (EMD Serono Press Release) - "The ELOWEN studies will be conducted in 266 sites in 26 countries. Each study will recruit approximately 200 lupus participants, and the primary endpoint will be a change in CLASI-A from baseline."

Trial status • Lupus

Effect of Renal Impairment on Enpatoran Pharmacokinetics (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Recruiting ➔ Completed | Trial completion date: Jul 2026 ➔ Apr 2026

Trial completion • Trial completion date • Renal Disease

Merck Announces First Dose in Phase 3 Study with Enpatoran for Lupus Patients with Active Skin Manifestations (Businesswire) - "ELOWEN-1 and ELOWEN-2 are two global randomized, double-blind, placebo-controlled Phase 3 studies evaluating enpatoran taken twice daily versus placebo, on top of standard of care, in patients with lupus who have active cutaneous manifestations. The ELOWEN studies will be conducted in 266 sites in 26 countries. Each study will recruit approximately 200 lupus participants, and the primary endpoint will be a change in CLASI-A from baseline."

Trial status • Lupus • Systemic Lupus Erythematosus

Elowen-1: A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (clinicaltrials.gov) - P3 | N=202 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

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