Santa Ana Bio Doses First Cohort in Phase 1 Trial of KIT/Siglec-6 Bispecific Antibody SAB01 for Mast Cell Depletion
核心洞察
Santa Ana Bio (搜索) has dosed the first cohort in a first-in-human Phase 1 trial of SAB01, a bispecific antibody that co-engages KIT (搜索) and Siglec-6 (搜索) to selectively deplete mast cells.
The randomized, double-blind, placebo-controlled single ascending dose study (NCT07815561) evaluates subcutaneous and intravenous SAB01 in healthy adults, with primary objectives of safety, pharmacokinetics, and pharmacodynamics.
SAB01 is designed to uncouple mast cell depletion from broad KIT (搜索) inhibition, potentially avoiding toxicities such as hematopoietic stem cell and melanocyte effects seen with existing KIT-targeted antibodies.
Santa Ana Bio (搜索) has dosed the first cohort in a first-in-human Phase 1 study of SAB01, a first-in-class bispecific antibody designed to selectively deplete mast cells through co-engagement of KIT (搜索) and Siglec-6 (搜索). The Alameda, California-based precision immunology company announced the milestone on Sept. 14, 2026, describing it as its transition into the clinic and the opening of a new approach to treating mast cell-driven disease.
A Conditional Depletion Strategy
SAB01 simultaneously engages KIT (搜索) and Siglec-6 (搜索), a receptor pair co-expressed on mast cells and not found together on any other cell type. According to the company, avidity-driven co-engagement of both receptors, combined with an extended half-life, restricts SAB01 activity to mast cells, selectively and durably depleting them while sparing other KIT-expressing cells.
The design addresses a limitation of existing KIT (搜索)-targeted antibodies, which drive rapid and deep responses in chronic urticaria but are not exclusive to mast cells. "KIT-targeted antibodies drive rapid and deep responses in chronic urticaria, but KIT isn't exclusive to mast cells, leading to toxicities from hitting other cell types, including hematopoietic stem cells and melanocytes," said Peter Emtage, founder and chief executive officer of Santa Ana Bio (搜索). "SAB01 was designed to uncouple mast cell depletion from broad KIT inhibition."
The off-target profile of monospecific KIT (搜索) inhibition has been observed clinically. 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.
Phase 1 Trial Design
The Phase 1 study (NCT07815561) is a randomized, double-blind, placebo-controlled, single ascending dose trial evaluating subcutaneous and intravenous SAB01 in healthy adult participants. Fifty-six participants will be enrolled across six subcutaneous cohorts and one intravenous cohort of eight participants each, randomized 6:2 to SAB01 or placebo. Primary objectives are safety, pharmacokinetics (PK), and pharmacodynamics (PD).
Further cohorts may be enrolled to evaluate select dose levels based on emerging safety, PK, and PD data. No efficacy or outcome data are available at this stage; the company has stated that safety, PK, and PD data from the single ascending dose study will inform decisions on whether and how to enroll any further cohorts.
"The initiation of this Phase 1 healthy volunteer study builds on extensive preclinical work supporting SAB01's conditional depletion of mast cells," said Newman Yeilding, M.D., chief medical officer of Santa Ana Bio (搜索). "The start of our Phase 1 study of SAB01 is the first step in bringing a truly selective and potentially safer mast cell targeted therapy to patients."
A Rapidly Evolving Urticaria Landscape
SAB01 enters a therapeutic area that has seen significant recent regulatory activity. Sanofi's Dupixent (dupilumab), an IL-4/IL-13 receptor blocker, received FDA approval for chronic spontaneous urticaria (搜索) (CSU) in adults and adolescents in April 2025 and was subsequently extended to children aged 2 to 11. Novartis's Rhapsido (搜索) (remibrutinib), a BTK inhibitor, was approved for antihistamine-refractory CSU in adults in September 2025 as the first oral targeted therapy in that setting.
Pipeline Beyond SAB01
Santa Ana Bio (搜索) describes itself as a biotechnology company developing a pipeline of therapeutics that leverage a multi-omics platform to advance precision medicines for autoimmune and inflammatory diseases. Beyond SAB01, the company's pipeline includes SAB05, a CD40 (搜索)-targeted glucocorticoid antibody-drug conjugate advancing through investigational new drug-enabling studies, with a clinic entry targeted for 2027.