Daiichi Sankyo's TLR7 Antagonistic Antibody DS-7011a Granted Clinical Approval in China for Systemic Lupus Erythematosus

The official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that DS-7011a, a Class 1 new drug applied for by Daiichi Sankyo, has been approved for clinical trials and is proposed for development forTreatment of Systemic Lupus Erythematosus (SLE). Public information shows that DS-7011a is aTargetedTLR7 Antagonistic Antibody，A Phase 1b/2 clinical study for the treatment of SLE and active cutaneous lupus erythematosus (CLE) is currently being conducted overseas.

Screenshot source: CDE official website

SLEIt is a chronic systemic autoimmune disease with clinical manifestations of multi-system damage symptoms, often leading to multi-organ and multi-system damage, posing a life-threatening major illness. The pathogenesis of SLE is complex, including the proliferation and activation of autoreactive T cells and B cells, the production of various pathogenic autoantibodies, abnormal cytokine secretion, and receptor expression.

Public information shows that Toll-like receptors (TLRs) are a class of innate immune sensors that can recognize conserved microbial structures. The activation of TLRs can initiate both innate and adaptive immune responses. TLR7, one of the TLRs members, is mainly distributed intracellularly in plasmacytoid dendritic cells (pDC) and B cells.Responsible for identifying pathogen single-stranded RNA,Plays an important role in the process of human recognition and clearance of pathogenic microorganisms. Existing research has shown[2]，TLR7 occupies a central position in the pathogenesis of systemic lupus erythematosus.TLR7GeneHighExpression drives the production of autoantibodies in SLE,TLR7Gain-of-function mutations also confer susceptibility to SLE.Antagonistic anti-mouse TLR7 monoclonal antibody improves survival and suppresses autoantibody production in NZBWF1 mice, which spontaneously develop lupus.

According to preclinical study data presented at the 2023 American College of Rheumatology (ACR),DS-7011a has the ability to inhibit TLR7-stimulated inflammatory cytokine production., and after 3 months of treatment (including the maximum administered dose), it showed no toxicity in monkeys. These findings suggest that by targeting and inhibiting TLR7, DS-7011a has the potential to become a promising therapeutic option for the treatment of SLE.

References:

[1]  Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Dec 20, 2023, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

[2] Targeting Toll-Like Receptor 7 with DS-7011a, a Promising Novel Antagonistic Antibody for the Treatment of Systemic Lupus Erythematosus. Retrieved Nov 13, 2023, from 

https://acrabstracts.org/abstract/targeting-toll-like-receptor-7-with-ds-7011a-a-promising-novel-antagonistic-antibody-for-the-treatment-of-systemic-lupus-erythematosus/

[3]ClinicalTrialsOfficial Website. From https://classic.clinicaltrials.gov/ct2/show/NCT05638802?term=DS-7011a&draw=2&rank=2