Akeso Inc (HKEX: 9926.HK), a China-based biopharmaceutical company, on Friday reported the preclinical research data for its novel antagonistic monoclonal antibody aimed at IL-1RAP, AK135, at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held in National Harbor, Maryland.

According to the company, the results demonstrated that AK135 effectively targets IL-1RAP and blocks three key pro-inflammatory signalling pathways--IL-1, IL-33, and IL-36 at their source, thereby halting the transmission of inflammatory signals. In preclinical models, AK135 provided significant pain relief in neuropathy, exhibiting dose-dependent efficacy, while also showing good tolerability and safety profiles.

In vitro results revealed that ELISA, Fortebio molecular interaction technology, and flow cytometry (FACS) results revealed that AK135 has high affinity for IL-1RAP, with binding activity comparable to or superior to that of the control antibody CAN04. Reporter gene assays further revealed that the product effectively inhibits the activation of IL-1, IL-33, and IL-36 signalling pathways, indicating excellent half-maximal inhibitory concentration (IC50) values in each of the pathways. In tumour cell models, the product is claimed to have significantly reduced the secretion of pro-inflammatory cytokines (such as IL-6 and IL-8) induced by IL-1, IL-33, and IL-36.

The in vitro experiments also revealed the high affinity and potent neutralising activity of AK135. To further assess its in vivo efficacy, the research team set up a Chemotherapy-induced peripheral neuropathy (CIPN) mouse model and evaluated the pharmacological impacts of AK135 through intermittent low-dose paclitaxel administration. Following AK135 treatment, the paw withdrawal threshold (PWT) in the CIPN model was significantly raised, indicating that the AK135 effectively alleviated mechanical allodynia, with a dose-dependent efficacy. Over the treatment period, mice in all dose groups maintained stable body weight, with no significant signs of toxicity, indicating good tolerance.