Celldex CDX-622 shows durable mast cell depletion in Phase 1 data

Celldex Therapeutics has reported first-in-human Phase 1 results for CDX-622, a bispecific antibody designed to deplete mast cells while simultaneously neutralising the alarmin cytokine TSLP. Data presented at the European Academy of Allergy and Clinical Immunology annual meeting in Istanbul showed rapid, dose-dependent, and durable reductions in serum tryptase, a recognised surrogate marker of tissue mast cell burden, with no dose-limiting toxicities and no related serious adverse events reported across any study part.

The Phase 1 trial enrolled 80 healthy participants across three parts: single ascending intravenous doses from 0.3 to 9.0 mg/kg, multiple ascending intravenous doses at the same range administered over six weeks, and single ascending subcutaneous doses of 290, 580, and 870 mg. No immunogenicity was detected at any dose, and the most commonly reported adverse event was Grade 1 headache. Biopsy data indicated a greater effect on mucosal mast cells than on skin mast cells, a distinction that may carry clinical relevance for airway and gastrointestinal indications.

Mechanism and platform significance

CDX-622 works by targeting soluble stem cell factor, the ligand required for KIT receptor-mediated mast cell survival and maturation, rather than blocking KIT directly. Celldex says this approach selectively inhibits KIT signalling in mast cells without measurable downstream effects on spermatogenesis or melanogenesis, findings supported by separately presented non-human primate data. The company positions itself as the first to demonstrate that neutralising soluble SCF can achieve selective mast cell inhibition, a claim the release does not qualify with an independent reference but which will be subject to peer scrutiny following full data publication.

Tibor Keler, co-founder and chief scientific officer, said the soluble-SCF approach "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." CDX-622 is now entering a Phase 1b proof-of-mechanism study in mild-to-moderate asthma, with subsequent studies in allergic rhinitis and food allergy flagged as near-term priorities.

Competitive and market context

Mast cell-targeted therapy has become one of the more contested spaces within immunology and allergy drug development. Celldex's own barzolvolimab, a monoclonal antibody that blocks the KIT receptor directly, is already in Phase 3 trials for chronic spontaneous urticaria and cold urticaria, giving the company a rare position of running parallel mast cell programmes with complementary mechanisms. AstraZeneca's tezepelumab, which also targets TSLP, is already approved in severe asthma, meaning CDX-622's TSLP arm enters a clinically validated but crowded field. The differentiation case for CDX-622 rests on the additive effect of simultaneous mast cell depletion, which no approved agent currently combines with TSLP blockade.

The broader I&I bispecific antibody market is expanding rapidly, with a number of programmes across Sanofi, AbbVie, and a range of clinical-stage biotechs pursuing dual-pathway approaches in atopic dermatitis, urticaria, and asthma. Celldex's Phase 1b readout in asthma will be a critical signal: healthy-participant tryptase data, while encouraging, does not speak to clinical efficacy in a disease population, and investors and partners will look for proof-of-mechanism data that links mast cell depletion to symptom control.

Celldex did not announce a partnership or licensing arrangement alongside the data presentation. The company said further pipeline updates, including additional bispecific candidates under the SCF-targeting platform, would be shared in future disclosures.