MAIA Biotechnology, Inc. (NYSE American: MAIA) is making strides in the development of its lead program, THIO, a potential first-in-class telomere-targeting agent for non-small cell lung cancer (NSCLC). The company announced promising interim data from its ongoing THIO-101 Phase 2 trial, revealing a 100% disease control rate (DCR) in second-line NSCLC patients. This data was presented at the Biotech Showcase 2024 investor conference.
The THIO-101 trial is a multicenter, open-label, dose-finding study evaluating THIO in combination with cemiplimab (Libtayo®) in patients with advanced NSCLC who have progressed after prior checkpoint inhibitor therapy. As of November 13, 2023, 60 patients had been dosed with THIO at varying dose levels (60mg, 180mg, or 360mg), with 42 having completed at least one post-baseline assessment. The primary objectives are to assess the safety, tolerability, and clinical efficacy of THIO, using Overall Response Rate (ORR) as the primary clinical endpoint.
Unprecedented Disease Control
The preliminary Phase 2 data has demonstrated unprecedented rates of disease control and response, vastly outperforming the standard of care for NSCLC. Specifically, the data showed a 100% DCR in second-line and 88% in third-line settings, among patients who had already progressed through previous lines of treatment. A 180mg/cycle dose of THIO was selected for THIO-101 based on stronger efficacy compared to other doses.
Telomere Targeting Mechanism
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is designed to target telomeres, which, along with the enzyme telomerase, are crucial for the survival and resistance of cancer cells. THIO induces telomerase-dependent telomeric DNA modification, leading to DNA damage responses and selective cancer cell death. The accumulation of THIO-damaged telomeric fragments in cytosolic micronuclei activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. Preclinical models have shown that sequential treatment with THIO followed by PD-(L)1 inhibitors results in significant tumor regression by inducing cancer type–specific immune memory.
Expanding the Pipeline
MAIA Biotechnology is also focusing on developing second-generation telomere-targeting agents. These new prodrugs, derived from lipid-modified THIO molecules, aim to improve specificity towards cancer cells and increase anticancer activity. The company's pipeline includes orphan drug designations for multiple hard-to-treat cancers, including glioblastoma.
Looking Ahead
MAIA anticipates multiple clinical milestones in 2024 as enrollment continues in the THIO-101 trial. Long-term efficacy data will be a major clinical inflection point. The company believes THIO holds significant potential as a second or later line of treatment for NSCLC patients who have progressed beyond standard checkpoint inhibitor regimens.
