Celldex Reveals Promising Preclinical Data for CDX-622 at AAAAI 2025

Celldex Therapeutics, Inc., a biotechnology firm based in Hampton, N.J., has revealed promising preclinical results for CDX-622, a novel bispecific antibody. This antibody targets two significant pathways related to inflammation and fibrosis, specifically thymic stromal lymphopoietin (TSLP) and mast cell exhaustion through stem cell factor (SCF) deprivation. The latest findings underline CDX-622's ability to neutralize SCF and TSLP, ultimately leading to a reduction in tissue mast cells and inhibiting Type 2 inflammatory responses. Such outcomes suggest that CDX-622 might offer improved clinical efficacy over single target treatments for inflammatory and fibrotic diseases.

These findings were shared by Dr. Diego Alvarado, Vice President of Research at Celldex Therapeutics, during a presentation at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. Dr. Tibor Keler, Executive Vice President and Chief Scientific Officer of Celldex, expressed optimism about the dual neutralization technique, highlighting its potential to significantly benefit patients suffering from conditions where both mast cells and TSLP are involved. Following these preclinical insights, Celldex is currently enrolling participants for a Phase 1 study in healthy volunteers, with initial data expected later in the year.

The preclinical studies highlighted CDX-622's effectiveness in inhibiting activities driven by TSLP and SCF in vitro, showing comparable potency to its parental monoclonal antibodies and other known treatments like tezepelumab and barzolvolimab. Notably, CDX-622 preferentially targets the soluble form of SCF over its membrane-bound form, which could influence various KIT-dependent processes differently. In a human skin explant model, CDX-622 effectively inhibited SCF and TSLP-dependent inflammatory patterns and demonstrated monoclonal antibody-like pharmacokinetic properties. Additionally, it significantly reduced skin mast cell markers and was well-tolerated in a toxicology study, even at the highest tested dose of 75 mg/kg, achieving substantial mast cell depletion across several tissues.

CDX-622 is specifically designed to address chronic inflammation by targeting two complementary and clinically validated pathways. One of its primary mechanisms involves neutralizing the alarmin TSLP while simultaneously depleting mast cells through SCF starvation. Given that SCF activates the KIT receptor essential for mast cell survival, targeting both SCF and TSLP with CDX-622 is expected to decrease tissue mast cells and Type 2 inflammatory responses, potentially providing enhanced therapeutic benefits for patients with inflammatory and fibrotic conditions.

Celldex Therapeutics has initiated a Phase 1 randomized, double-blind, placebo-controlled trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of CDX-622. This study involves administering single ascending doses in its first part and multiple ascending doses in the second part, involving up to 56 healthy participants. Recruitment for this trial is actively ongoing.

Celldex Therapeutics is a biotechnology company at the forefront of scientific advancements in mast cell biology and the development of transformative treatments. Its pipeline comprises antibody-based therapies that engage the human immune system and influence critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune, and other serious diseases.