In vitro potency and pharmacokinetics of APG777, a novel anti-IL-13 mAb

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.

We sought to investigate the in vitro potency and in vivo pharmacokinetics of APG777.

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.

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.

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.