Novel telomere-targeting therapy for advanced non-small cell lung cancer

Maia Biotechnology, Inc. received a $770,168 Project Grant from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) awarded on September 9, 2025, with a completion date of August 31, 2028. The award funds a Phase 2 multicenter clinical trial evaluating THIO, a novel telomere-targeting therapeutic agent, in combination with the immune checkpoint inhibitor cemiplimab for treating patients with advanced stage 3 or 4 non-small cell lung cancer (NSCLC) who have demonstrated resistance to prior checkpoint inhibitor treatments. THIO is designed to exploit cancer cells' dependency on telomerase by incorporating into telomeres and inducing cellular instability, with preclinical and early clinical data demonstrating high selectivity for telomerase-active cancer cells and significant synergistic potential with checkpoint inhibitors.

The project deliverables include the design, execution, and evaluation of a single-arm, open-label clinical trial assessing the safety and efficacy of the THIO-cemiplimab combination in checkpoint inhibitor-resistant NSCLC patients. Success of this investigational approach could provide an effective treatment option for a significant portion of advanced NSCLC patients who currently lack efficacious standard therapeutic alternatives, while advancing understanding of telomere-targeting cancer biology with potential applications to other telomerase-positive malignancies.

Abstract

With non-small cell lung cancer (nsclc) persisting as a leading cause of cancer mortality worldwide and resistant to many standard treatments, maia biotechnology, INC. Is focused on developing thio, a novel therapeutic agent aimed at improving treatment outcomes in patients with advanced-stage nsclc. Thio, a direct telomere targeting agent, is designed to exploit the vulnerability of cancer cells' telomerase-dependency, offering a new avenue for therapeutic intervention in cases where existing options fail. To address the limited efficacy and resistance issues associated with current nsclc treatments, our objective is to evaluate the safety and efficacy of thio in combination with the immune checkpoint inhibitor cemiplimab in a multicenter, open- label, single-arm phase 2 clinical study. The study will enroll subjects with stage 3 or 4 nsclc who have shown resistance to prior checkpoint inhibitors, utilizing thio's mechanism of causing tumor cell death by incorporation into telomeres and inducing instability. This phase 2 clinical trial follows promising preclinical and early clinical results where thio showed high selectivity in killing telomerase-active cancer cells and significant synergy with immune checkpoint inhibitors. Given the high incidence of nsclc and the significant portion of patients lacking effective treatment options, the successful development of thio could dramatically enhance quality of life and survival rates by providing a new, effective treatment modality. This project not only addresses an urgent public health need but also advances our understanding of cancer biology and treatment, potentially offering broader implications for other telomerase-positive cancers.