Phase 2 ateganosine (THIO) telomere-targeting nucleoside sequenced with PD-1 inhibitor cemiplimab

MAIA Biotechnology’s multicenter, open-label Phase 2 THIO-101 study tests whether ateganosine (THIO; 6‑thio‑2′‑deoxyguanosine), a telomere-targeting small-molecule nucleoside, can re-sensitize immune-checkpoint–experienced NSCLC when given before cemiplimab (Libtayo), a PD‑1 (CD279)–blocking monoclonal antibody from Regeneron/Sanofi. THIO is designed to be preferentially incorporated into telomeres in telomerase-positive tumor cells, driving telomere uncapping, genomic instability, and tumor cell death—potentially creating immunogenic damage that improves subsequent PD‑1 activity. The trial includes dose-finding and expansion components (Parts A/B) and later-line efficacy comparisons (Parts C/D), including sequential THIO→cemiplimab versus THIO alone in third-line advanced/metastatic disease after secondary resistance/relapse on prior PD‑1/PD‑L1 therapy. The key scientific angle is the “sequencing” strategy: using telomere-directed damage as an immune priming step rather than combining concurrently. For these patients today, care after progression on first-line immunotherapy typically becomes platinum doublet chemotherapy (if not already used), then docetaxel ± ramucirumab, and/or histology-appropriate options and clinical trials; targeted therapy applies only when actionable drivers (EGFR/ALK/ROS1/etc.) are present, leaving a sizable group reliant on non-curative later-line chemo.