D3.165 - Phase 1 study of CDX-622, a bispecific antibody targeting TSLP and mast cells via stem cell factor

Heterogeneity in the pathophysiology of many chronic inflammatory disorders can limit the effectiveness of targeted therapies. Mast cells (MCs) and the alarmin thymic stromal lymphopoietin (TSLP) may contribute to the pathology of several of these diseases through largely non-redundant mechanisms. Thus, combined reduction of MCs through stem cell factor (SCF) neutralization with inhibition of TSLP with a single bispecific antibody may result in broader efficacy in diseases where both mechanisms are implicated, such as asthma.

A double-blind randomized placebo-controlled Phase 1 study (NCT06650761) was conducted to assess the safety, pharmacokinetics (PK) and pharmacodynamic impact of CDX-622, a first-in-class bispecific antibody that inhibits SCF and TSLP, in healthy participants. This three-part study evaluated intravenous (IV) doses of CDX-622 at 0.3, 1, 3 and 9 mg/kg in the single ascending dose (SAD) portion of the study (Part 1); 1, 3 and 9 mg/kg q2w x4 in the multiple ascending dose (MAD) portion (Part 2), and single ascending subcutaneous (SC) 290, 580, and 870 mg doses (Part 3). In each cohort, 6 participants were administered CDX-622 and 2 were administered placebo. Part 1 is complete, and participants in Parts 2 and 3 have completed dosing.

85 participants were enrolled in this Phase 1 study of which 80 completed treatment. CDX-622 was well tolerated with no dose-limiting toxicities (DLT), or related serious adverse events (SAE). Rapid, profound and durable reductions in serum tryptase, a circulating marker of mast cell load, were observed, which were greater with higher exposures. CDX-622 exhibited antibody-like PK with a terminal half-life of 24 days and good bioavailability with SC administration. 

CDX-622 demonstrated a favorable safety profile, antibody-like PK with good bioavailability, and a profound impact on serum tryptase, indicative of MC depletion. CDX-622 represents the first molecule that depletes mast cells via SCF neutralization to enter human clinical trials. Combined TSLP neutralization and MC depletion with CDX-622 may result in broader efficacy in inflammatory diseases where both pathways play a pathogenic role.