Background:IL-13 plays a key role in the induction and perpetuation of type 2 immune responses associated with the development of atopic dermatitis and other chronic inflammatory diseases. mAbs targeting IL-13 have demonstrated efficacy in IL-13-driven diseases; however, current therapeutics require dosing every 2 to 4 weeks, resulting in significant injection burden for patients. APG777 is a humanized, IgG1 IL-13-targeting mAb that has been engineered to have an optimized pharmacokinetic profile, allowing for less frequent dosing.
Objective:We sought to investigate the in vitro potency and in vivo pharmacokinetics of APG777.
Methods:The affinity of APG777 was characterized using surface plasmon resonance; the half-maximal inhibitory concentration (IC50) of APG777 was determined in various in vitro assays measuring inhibition of IL-13 signaling via signal transducer and activator of transcription 6 phosphorylation and chemokine release in relevant cell lines. Pharmacokinetics of APG777 were evaluated in nonhuman primates following a single intravenous or subcutaneous infusion. All studies included lebrikizumab produced based on the publicly available sequence as key comparator.
Results:APG777 demonstrated a similar in vitro potency across numerous assays compared with lebrikizumab and a 2-fold longer serum half-life following subcutaneous injection in nonhuman primates.
Conclusions:These data provide evidence in support of the clinical potential of APG777 in diseases where IL-13 signaling is a main driver of the inflammatory response. The prolonged half-life of APG777 may enable less frequent dosing compared with current treatments, which could reduce injection burden and increase compliance. APG777 is currently being investigated in a phase 2 randomized, controlled trial in patients with atopic dermatitis.