Immunology

NuCerin is developing HY209, an oral formulation that targets the GPCR19-P2X7R pathway to inhibit the activation of the NLRP3 inflammasome, as a novel therapeutic candidate for Alzheimer’s disease.

Unlike conventional Alzheimer’s drugs, which primarily aim to prevent the formation or deposition of beta-amyloid or remove abnormal tau proteins to protect neurons, Shaperon's HY209 works by fundamentally reducing neuroinflammation. This mechanism activates immune cells responsible for clearing biological waste such as beta-amyloid and alleviates neuroinflammation to protect nerve cells.

In the 5XFAD transgenic mouse model of Alzheimer’s disease, treatment with HY209 increased the expression of GPCR19, which is typically reduced in the brain tissue, while decreasing the expression of the pro-inflammatory receptor P2X7. It was also confirmed that HY209 broadly suppressed inflammation-related signaling networks in the brain, including pro-inflammatory cytokines such as IL-1β, IL-18, and TNF-α.

Histological analysis of mouse brain tissue following 10 weeks of HY209 administration showed a reduction in beta-amyloid plaques, decreased microgliosis, an increase in the anti-inflammatory marker CD47, and improvement in cognitive and memory functions.

Currently, a Phase 1 clinical trial is underway in healthy volunteers. Based on safety data from the single-dose study, the trial is progressing to evaluate safety and tolerability with repeated dosing.