Signal Transduction and Targeted Therapy· 2026Q1
Targeting an IL-17/IL-36 pathogenic hub in hidradenitis suppurativa with a bispecific antibody
- 0citations
- Q1SCImago
- 2026year
Short summary
A bispecific antibody, HB0043, targeting both IL-17 and IL-36 pathways, demonstrated significant clinical improvement in severe hidradenitis suppurativa (HS) patients, including an 82.13% reduction in inflammatory lesions and tunnel regression.
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Key points
- HB0043, a bispecific antibody, targets synergistic IL-17/IL-36 inflammatory circuits in HS.
- In a trial of severe HS patients (NCT06895499), HB0043 achieved an 82.13% mean reduction in inflammatory lesions by week 16.
- 100% of patients achieved HiSCR50, and 80% achieved HiSCR75, with concurrent ultrasound-confirmed tunnel regression.
- The treatment suppressed systemic inflammation and restored metabolic homeostasis.
AI-generated from the title and abstract; the full text is not read.
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with a high unmet need, particularly for treatment-resistant tunnels. Integrated multiomics analysis revealed that HS tunnels are spatially organized, self-amplifying inflammatory circuits driven by synergistic IL-17/IL-36γ activation of a unique keratinocyte subset, which activates neutrophils and inflammatory fibroblasts. This mechanistic insight coupled with spatial coenrichment of IL-17A and IL-36R provided the rationale for HB0043, a bispecific antibody that leverages IL-36R binding to locally dual-block both cytokines. HB0043 outperformed IL-17A/IL-17F bispecific and parental antibodies in vitro. In a proof-of-concept trial (NCT06895499) involving severe, tunnel-dominant Hurley Stage III HS patients, HB0043 induced promising clinical responses. At week 16, patients demonstrated an 82.13% mean percentage reduction from baseline in total abscess and inflammatory nodule count (AN), while 100% and 80% achieved HiSCR50 and HiSCR75, respectively, alongside ultrasound-confirmed tunnel regression and no major short-term safety signals. Longitudinal plasma proteomics showed suppressed inflammation and restored metabolic homeostasis. By tracking these dynamic systemic alterations alongside local structural changes, our multiomics approach bridges the gap between focal tissue lesions and global systemic disease activity. These findings establish dual blockade of IL-17A and IL-36R as a potential therapeutic strategy, offering a targeted strategy for recalcitrant disease that effectively improves the anatomical therapeutic barriers of advanced hidradenitis suppurativa, thereby demonstrating that cross-pathway bispecific antibodies can dismantle complex inflammatory circuits to achieve structural tissue healing where traditional monotherapies consistently fail.
The authors' abstract, as published at the source. Signal Transduction and Targeted Therapy, 2026 · DOI ↗
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Field: Dermatology
DermatologyMedicine