Discovery

Shandong First Medical researchers identify IL-17A/IL-36 axis as therapeutic target in HS

Edited by Robert McTiernan··2 min read
Shandong First Medical researchers identify IL-17A/IL-36 axis as therapeutic target in HS

HB0043, a bispecific antibody targeting IL-17A and IL-36R, achieved a 100% HiSCR50 response rate and an 82.13% mean reduction in abscess and inflammatory nodule count at week 16 in a 15-patient, open-label proof-of-concept trial in hidradenitis suppurativa (HS), according to a study published in Signal Transduction and Targeted Therapy. ​

Researchers at the Dermatology Hospital of Shandong First Medical University in China combined single-cell RNA sequencing, spatial transcriptomics, and plasma proteomics from 11 HS patients with in vitro experiments and a Phase I/II clinical trial (NCT06895499) involving 15 patients with moderate-to-severe, predominantly Hurley stage III, tunnel-dominant disease.

The multiomics analysis identified a self-amplifying inflammatory circuit within HS tunnels driven by synergistic IL-17A and IL-36γ activity: tunnel-resident keratinocytes co-express IL-36γ and IL-17-responsive genes, IL-36γ induces IL-17A production in T cells, and the resulting feedback loop activates inflammatory fibroblasts and recruits neutrophils.

HB0043 was designed around a spatial observation from the tissue data: IL-17A is co-enriched around IL-36R-expressing cells in tunnel lesions, so binding IL-36R concentrates IL-17A neutralization at the primary site of disease. In vitro, HB0043 outperformed both an IL-17A/IL-17F bispecific and parental antibodies, though assay details are not provided.

In the 15-patient clinical cohort, HB0043 achieved HiSCR50 in 100% of patients and HiSCR75 in 80% at week 16, with ultrasound confirming tunnel regression and no major short-term safety signals reported. However, the uncontrolled study design and small patient population prevent conclusions about comparative efficacy.

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The authors note that monoclonal agents targeting only one of these pathways, including adalimumab, secukinumab, and bimekizumab, typically yield HiSCR50 responses in 40%–60% of patients. The IL-36R inhibitor spesolimab previously showed limited efficacy on the primary endpoint of a randomized Phase II HS trial, although improvements in draining tunnels were observed. The authors propose that simultaneously blocking IL-17A and IL-36R could provide broader suppression of the inflammatory pathways involved in HS.

The authors acknowledge that the cohort was small, predominantly young males with Hurley Stage III tunnel-dominant disease, contrasting with the female-predominant epidemiology typical of Western populations, and that larger randomized controlled trials are needed. HB0043 is sponsored by Shanghai Huaota Biopharmaceutical Co., Ltd. and is currently in Phase I/II development.

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