E6742 / Eisai - LARVOL DELTA

Safety, Biomarker Response, and Efficacy of E6742, a Dual Antagonist of Toll-Like Receptor 7 and 8, in a First-in-Patient, Randomized, Double-Blind, Phase1/2 Study in Systemic Lupus Erythematosus (ACR Convergence 2024) - P1/2 | "E6742 had a favorable safety profile and was well tolerated, with marked IGS responses, proinflammatory cytokines responses and sufficient efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials."

Biomarker • Clinical • IO biomarker • P1/2 data • Dermatitis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus • IFNA1 • IL1B • IL6 • TLR7

Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first in patient, randomised, double-blind, phase I/II study in systemic lupus erythematosus. (PubMed, RMD Open) - P1/2 | "E6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials."

Biomarker • Clinical • IO biomarker • Journal • P1/2 data • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

SAFETY, PHARMACOKINETICS, BIOMARKER, AND EFFICACY OF E6742, A DUAL ANTAGONIST OF TOLL-LIKE RECEPTOR 7 AND 8, IN A FIRST-IN-PATIENT PHASE1/2 STUDY IN SYSTEMIC LUPUS ERYTHEMATOSUS (EULAR 2024) - P1/2 | "E6742 was well tolerated in patients with SLE and demonstrated a favorable safety profile. In addition, E6742 provided a markedly improved IGS response, and sufficient efficacy signals regardless the short treatment duration. These results provide the first clinical evidence to suggest that E6742 as a first-in-class TLR7/8 inhibitor, could potentially be beneficial for SLE, and support the longer-term, larger clinical trials of E6742."

Biomarker • Clinical • IO biomarker • P1/2 data • PK/PD data • Cutaneous Lupus Erythematosus • Dermatitis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7 • TLR8

Can Innate Immune System Be Targeted Directly in Lupus? (MedPageToday) - P1/2 | N=26 | NCT05278663 | Sponsor: Eisai Co., Ltd. | "Twelve weeks of treatment with a bivalent agent called E6742 that targets TLR-7 and TLR-8 led to improvements in British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responses in 57.1% of patients receiving 200 mg twice daily, compared with 33.3% of a placebo group, according to Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health in Fukuoka, Japan, and colleagues...By targeting these receptors directly, Tanaka and colleagues hoped to shut down lupus pathology at the earliest point in the process, preventing interferon release and the subsequent autoimmune activity...Mean patient age was about 38 and some 90% were women. Disease duration averaged about 7 years. At baseline, SLE Disease Activity Index-2000 (SLEDAI-2K) scores averaged 7.7; Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores averaged 3.6."

P1/2 data • Systemic Lupus Erythematosus

A new therapeutic target for systemic lupus erythematosus: the current landscape for drug development of a toll-like receptor 7/8 antagonist through academia-industry-government collaboration. (PubMed, Immunol Med) - P1, P1/2 | "One of the potential benefits of this program is to conduct academia-led clinical research to identify specific biomarkers for E6742 in parallel with clinical studies (UMIN000042037). The aim of this review is to present current progress within the strategic collaboration of the AMED CiCLE program that optimize clinical development for patients with SLE."

IO biomarker • Journal • Review • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants (clinicaltrials.gov) - P1/2 | N=26 | Completed | Sponsor: Eisai Co., Ltd. | Active, not recruiting ➔ Completed

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

A novel Toll-like receptor 7/8-specific antagonist E6742 Ameliorates clinically relevant disease parameters in murine models of lupus. (PubMed, Eur J Pharmacol) - "In two mouse models of lupus, oral dosing of E6742 after the onset of disease suppressed increase in autoantibodies and blocked the advance of organ damage. Collectively, the data show that TLR7/8 activation contributes to disease progression and its blocking by E6742 has potential as a therapeutic intervention for lupus."

Journal • Preclinical • Immunology • Inflammatory Arthritis • Lupus • TLR7 • TLR8

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Recruiting ➔ Active, not recruiting

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

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Jul 2023 ➔ Oct 2023 | Trial primary completion date: Jul 2023 ➔ Oct 2023

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

First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742, a Dual Antagonist of Toll-like Receptors 7 and 8, in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "In addition to safety and good tolerability, this study demonstrated cytokine concentrations in cultured peripheral blood in response to E6742 were suppressed in a dose-dependent manner. Further clinical studies targeting systemic lupus erythematosus patients are currently underway."

Journal • P1 data • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR8

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Eisai Co., Ltd. | Not yet recruiting ➔ Recruiting

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

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Eisai Co., Ltd.

New P1/2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study to Assess the Safety and Tolerability of E6742 in Japanese Healthy Adult Participants (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Eisai Co., Ltd.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety and Tolerability of E6742 in Japanese Healthy Adult Participants (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Eisai Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Assess the Safety and Tolerability of E6742 in Japanese Healthy Adult Participants (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Eisai Co., Ltd.

Clinical • New P1 trial

Eisai Enters Joint Research Alliance to Create SLE Treatment (Contract Pharma) - "Eisai Co., Ltd. has entered into an industry-academia-government joint research agreement with four universities in Japan concerning the 'Industrialization of Japan-originated Toll-like receptor research by Academia-Industry collaborating All-Japan system: Creation of new drug for SLE treatment'...Eisai aims to create a Japan-originated therapeutic drug for systemic lupus erythematosus (SLE) through industry-academia-government collaboration, using its in-house discovered new oral Toll-Like Receptor (TLR) 7/8 inhibitor E6742."

Licensing / partnership • Lupus