MAIA-2022-12

MAIA-2022-12 is a second-generation, small molecule telomerase inhibitor developed by MAIA Biotechnology. It is a lipid-conjugated prodrug derived from THIO (6-thio-2’-deoxyguanosine), belonging to a new chemical class called telomere targeting divalent dinucleotides. The drug is designed to induce telomerase-dependent modification of telomeric DNA in cancer cells, leading to DNA damage responses and selective cancer cell death. Preclinical studies have shown that MAIA-2022-12 demonstrates significant anti-tumor activity both as a single agent and in combination with immune checkpoint inhibitors (such as anti-PD-L1 antibodies), overcoming immunotherapy resistance and resulting in tumor growth inhibition across multiple cancer models including lung cancer, colorectal carcinoma, melanoma, and hepatocellular carcinoma. The mechanism involves not only direct cytotoxicity but also activation of innate (cGAS/STING) and adaptive (T-cell) immune responses through the accumulation of damaged telomeric fragments in cytosolic micronuclei[1][2][6].