Celldex's Bispecific CDX-622 Shows Rapid Mast Cell Depletion and Favorable Safety in First-in-Human Phase 1 Trial
核心洞察
Celldex (搜索) presented positive Phase 1 results for CDX-622, a novel bispecific antibody targeting soluble SCF (搜索) and TSLP (搜索), at the EAACI Annual Meeting in Istanbul.
CDX-622 demonstrated rapid, profound, dose-dependent, and durable reductions in serum tryptase, indicating effective mast cell depletion, and was well-tolerated at all dose levels.
The company is the first to demonstrate that neutralizing soluble stem cell factor can selectively inhibit KIT (搜索) signaling in mast cells without measurably impacting other KIT-dependent functions.
Celldex (搜索) Therapeutics presented positive first-in-human results from its Phase 1 study of CDX-622, a novel bispecific antibody, at the European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting in Istanbul, Türkiye, on June 14, 2026. The data demonstrated that CDX-622 induced rapid, durable, dose-dependent reductions in serum tryptase — a biomarker indicative of mast cell depletion — and was well-tolerated across all dose levels tested.
CDX-622 is a uniquely engineered bispecific antibody that simultaneously targets soluble stem cell factor (SCF (搜索)) and thymic stromal lymphopoietin (TSLP (搜索)), two independent and clinically validated pathways implicated in the pathology of multiple allergic and inflammatory disorders. By neutralizing soluble SCF, CDX-622 starves mast cells of a critical survival signal via the KIT (搜索) receptor, while TSLP neutralization inhibits Type 2 inflammatory responses. The antibody has been engineered with disabled effector function (AQQ) and an extended half-life (YTE).
"Celldex (搜索) continues to drive groundbreaking science and is the first company to directly demonstrate that neutralizing soluble stem cell factor can selectively inhibit KIT (搜索) signaling in mast cells, a historically challenging target," said Tibor Keler, Ph.D., Co-founder, Executive Vice President and Chief Scientific Officer at Celldex. "Importantly, the approach of targeting soluble SCF (搜索) provides a promising anchor mechanism enabling the development of a robust portfolio of bispecific candidates designed to overcome the heterogeneity inherent in the pathophysiology of many inflammatory diseases."
Phase 1 Study Design and Key Findings
The Phase 1 trial was a randomized, double-blind, placebo-controlled, dose escalation study conducted in healthy participants across three parts. Part 1 enrolled 32 participants across four cohorts receiving single ascending intravenous doses of CDX-622 (0.3, 1.0, 3.0, and 9.0 mg/kg), with observation over 12 weeks. Part 2 enrolled 24 participants across three cohorts receiving multiple ascending intravenous doses (1.0, 3.0, and 9.0 mg/kg at weeks 2, 4, and 6), observed for 18 weeks. Part 3 enrolled 24 participants across three cohorts receiving single ascending subcutaneous doses (290, 580, and 870 mg), observed for 12 weeks. Each cohort randomized six participants to CDX-622 and two to placebo.
Rapid, profound, dose-dependent, and durable reductions in serum tryptase were observed, indicative of tissue mast cell inhibition and depletion. Notably, tryptase decreases were comparable to KIT (搜索)-targeting approaches following multiple doses. Biopsy data suggested a greater impact on mucosal mast cells than on skin mast cells.
CDX-622 exhibited monoclonal antibody-like pharmacokinetics, with an extended half-life and good exposure following subcutaneous administration, consistent with good bioavailability. No evidence of immunogenicity was detected at any dose level.
Safety and Tolerability
CDX-622 was well-tolerated in all study parts and at all dose levels. There were no dose-limiting toxicities or related serious adverse events. The most commonly reported adverse event across the study was Grade 1 headache. Importantly, there were no changes in hair or skin pigmentation and no meaningful impact on hematologic parameters — findings that underscore the selectivity of targeting soluble SCF (搜索) without disrupting other KIT (搜索)-dependent physiological functions.
Preclinical Validation
In complementary findings presented at the European Mast Cell and Basophil Research Network (EMBRN) meeting, Celldex (搜索) reported new non-human primate data validating the soluble SCF (搜索)-targeting approach. The preclinical study compared antibodies targeting soluble SCF versus those targeting both soluble and membrane-bound SCF. Results showed that targeting soluble SCF effectively depleted mast cells similarly to membrane SCF targeting, but without measurable effects on spermatogenesis or melanogenesis.
Strategic Pipeline Implications
"Barzolvolimab and CDX-622 target mast cells through two distinct, highly synergistic platform approaches. Together, these novel candidates build a powerful foundation for a broad portfolio of therapeutics targeting a wide range of inflammatory diseases where mast cells are implicated," said Anthony Marucci, Co-Founder, President and Chief Executive Officer at Celldex (搜索).
CDX-622 is currently being evaluated in a Phase 1b proof-of-mechanism study in mild to moderate asthma (搜索). Celldex (搜索) has indicated plans to initiate additional proof-of-concept studies in allergic rhinitis (搜索) and food allergy (搜索), indications where both mast cells and TSLP (搜索) play a pathogenic role. The company's broader pipeline includes barzolvolimab, a humanized monoclonal antibody targeting the KIT (搜索) receptor, currently in Phase 3 studies for chronic spontaneous urticaria (搜索) and cold urticaria/symptomatic dermographism, as well as Phase 2 studies in prurigo nodularis and atopic dermatitis.