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AK135 is a novel antagonistic monoclonal antibody targeting the interleukin-1 receptor accessory protein (IL-1RAP), developed by Akeso, Inc. IL-1RAP is a critical co-receptor for several members of the IL-1 family, including IL-1, IL-33, and IL-36. By binding to IL-1RAP, AK135 simultaneously inhibits these three pro-inflammatory signaling pathways, which are implicated in the pathogenesis of neuroinflammation and neuropathic pain. The drug is primarily being developed for the treatment of chemotherapy-induced peripheral neuropathy (CIPN), a common and debilitating side effect of cancer treatment that currently lacks approved therapies. Preclinical studies presented at SITC 2025 demonstrated that AK135 has high affinity for IL-1RAP and effectively reduces mechanical allodynia and the release of pain-related cytokines in dose-dependent manners. As of late 2025, AK135 is undergoing Phase I clinical evaluation to assess its safety, tolerability, and preliminary efficacy in patients with malignant tumors suffering from CIPN.
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