AT A GLANCE

An investigational study demonstrated that SAR442970, a bispecific Nanobody targeting TNF-α and OX40L, delivered superior immune suppression in both animal and human-derived models of inflammation. The findings highlight OX40-OX40L signaling as a central driver in HS and support ongoing clinical development of this dual-target therapy.

Hidradenitis suppurativa (HS) has long resisted effective control, with many therapies falling short of fully quelling chronic inflammation. A new investigational biologic, SAR442970, leverages dual targeting of two key immune pathways—TNF-α and OX40L—demonstrating superior efficacy over monotherapy in both preclinical and translational models. The bispecific Nanobody was evaluated in graft-versus-host disease mouse models, immune response assays in cynomolgus monkeys, and patient-derived HS tissue samples. Across all models, SAR442970 significantly outperformed single-agent blockade, suppressing both cellular and humoral immune responses.

Notably, inflamed monkey skin treated with SAR442970 showed reversal of disease-associated gene expression patterns, closely mirroring those in human HS and atopic dermatitis. OX40-expressing T cells were identified as a highly migratory, pathogenic population in HS lesions, further strengthening the case for OX40-OX40L as a pivotal axis in disease progression. The combination strategy of TNF-α and OX40L inhibition thus represents a mechanistically grounded therapeutic innovation. SAR442970 is currently under evaluation in a phase 2 clinical trial, aiming to bring a much-needed advance to the HS treatment landscape.

Reference: Leeuw T, Šimaitė D, Heyninck K, et al. Combined TNF-α and OX40L targeting as a new treatment option for hidradenitis suppurativa. J Allergy Clin Immunol Glob. 2025;4(3):100483. Published 2025 Apr 23. doi:10.1016/j.jacig.2025.100483

DRUG AT A GLANCE

SAR442970 is a bispecific, pentavalent Nanobody designed to simultaneously inhibit TNF-α and OX40L, key drivers of inflammation. Engineered with an extended serum half-life, it suppresses both humoral and cellular immune responses and has shown superior activity over monotherapies in multiple animal models. Its ability to reverse disease-related gene signatures in HS-related tissue positions it as a novel therapeutic candidate. SAR442970 is currently in phase 2 trials for hidradenitis suppurativa.