California-based Santa Ana Bio has dosed the first cohort in a first-in-human trial of SAB01, a bispecific antibody designed to deplete mast cells selectively by co-engaging KIT and Siglec-6. The molecule's design addresses the following: existing KIT-targeted antibodies produce rapid responses in conditions such as chronic urticaria but also hit hematopoietic stem cells and melanocytes, generating off-target toxicity. Because KIT and Siglec-6 are co-expressed on mast cells but not found together on any other cell type, SAB01's avidity-driven dual engagement is intended to restrict activity to mast cells while sparing other KIT-expressing populations.

The Phase I study (NCT07815561) is a randomized, double-blind, placebo-controlled, single ascending dose trial enrolling up to 88 healthy adults, randomized 6:2 to SAB01 or placebo. Primary objectives are safety, pharmacokinetics (PK), and pharmacodynamics (PD). No efficacy or outcome data are available at this stage; additional cohorts may be added based on emerging safety and PK/PD findings.

Sanofi's Dupixent (dupilumab), an IL-4/IL-13 receptor blocker, received FDA approval for chronic spontaneous urticaria (CSU) in adults and adolescents in April 2025 and was subsequently extended to children aged 2 to 11. Novartis's Rhapsido (remibrutinib), a BTK inhibitor, was approved for antihistamine-refractory CSU in adults in September 2025 as the first oral targeted therapy in that setting. Separately, barzolvolimab, a monospecific anti-KIT antibody in development at Celldex Therapeutics, has shown on-target effects in other KIT-expressing tissues, including hair-color changes and neutropenia.

Santa Ana said the Phase I initiation marks its first entry into the clinic. The company's broader pipeline includes SAB05, a CD40-targeted glucocorticoid antibody-drug conjugate advancing through investigational new drug-enabling studies, with a clinic entry targeted for 2027. Safety, PK, and PD data from the SAB01 single ascending dose study will inform decisions on whether and how to enroll any further cohorts.

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