Advancements in Atopic Dermatitis Treatment: A Focus on NM26-2198, a Dual-Targeting Bispecific Antibody

NM26-2198 is a promising candidate for clinical trials due to its favorable non-clinical pharmacodynamics, pharmacokinetics, and toxicology profile. It is designed to enhance the management and well-being of individuals with moderate to severe atopic dermatitis (AD). The drug is a tetravalent bispecific IgG4-scFv fusion antibody that targets both the alpha chain of the interleukin-4 receptor (IL-4Rα) and interleukin-31 (IL-31), effectively blocking the proinflammatory cytokines IL-4, IL-13, and the itch-inducing IL-31.

In vitro and ex vivo studies have confirmed NM26-2198's high affinity for its targets and its capacity to inhibit the signaling pathways triggered by IL-4, IL-13, and IL-31. It has been shown to be more effective than single-pathway inhibition, as demonstrated by its superior suppression of CCL2 release from bronchial epithelial cells and TARC (CCL17) release from whole blood assays. The drug also effectively reduces CD23 upregulation in human primary B cells and monocytes.

Furthermore, ex vivo experiments using human skin samples have indicated that NM26-2198 can prevent the abnormal gene expression caused by the aforementioned cytokines. In vivo studies in cynomolgus monkeys have confirmed the drug's ability to mitigate IL-31-induced pruritus.

A 4-week GLP toxicology study in cynomolgus monkeys demonstrated that NM26-2198 is well-tolerated, with no adverse toxicities observed at doses up to 125 mg/kg administered weekly for a total of five doses. This dose has been identified as the no observed adverse effect level (NOAEL) for the drug.

With these findings, a first-in-human single ascending dose (SAD) study is being planned for healthy volunteers, which will be followed by a multiple ascending dose (MAD) study in patients with moderate to severe AD. Despite advancements in AD treatments, there remains a significant need for therapies that can reduce the disease's impact on patients' quality of life, and NM26-2198 holds potential in this regard.