{"entity":{"id":"ateganosine","kind":"drug","name":"Ateganosine (THIO)","aka":["THIO","6-thio-dG","6-thio-2'-deoxyguanosine","beta-thioguanine deoxyriboside"],"tldr":"Ateganosine (THIO) is an experimental drug from MAIA Biotechnology that is built into the ends of chromosomes by telomerase, an enzyme most cancers switch on, and damages them. It is being tested before the immunotherapy cemiplimab in advanced non-small cell lung cancer.","summary":"Ateganosine is the international non-proprietary name of 6-thio-2'-deoxyguanosine, which MAIA Biotechnology develops as THIO; the NCI Thesaurus lists ateganosine as a synonym of beta-thioguanine deoxyriboside. Mender and colleagues (Cancer Discovery 2015) showed that it is recognised by telomerase and incorporated into newly synthesised telomeres, causing telomere dysfunction only in cells expressing telomerase; most cancer cell lines died rapidly while normal fibroblasts and colonic epithelial cells were largely unaffected, and it slowed A549 lung cancer xenograft growth more than 6-thioguanine. A 2020 Cancer Cell paper from the same group linked the resulting telomere stress to STING-dependent anti-tumour immunity, the rationale for giving it before a checkpoint inhibitor.\n\nIn the clinic MAIA sequences low-dose ateganosine before cemiplimab in advanced non-small cell lung cancer after a checkpoint inhibitor has failed: THIO-101 (NCT05208944, phase 2, active, not recruiting) and a phase 3 trial against chemotherapy in the third line (NCT06908304, recruiting since December 2025). MAIA states that THIO with Libtayo has not been proven safe and effective. No efficacy results are recorded here.","status":"phase-3","asOf":"2026-11-03","links":[{"label":"MAIA Biotechnology: ateganosine (THIO) programme","url":"https://maiabiotech.com/pipeline/thio/"},{"label":"Mender et al. 2015, Cancer Discovery: induction of telomere dysfunction by 6-thio-2'-deoxyguanosine","url":"https://doi.org/10.1158/2159-8290.CD-14-0609"},{"label":"Mender et al. 2020, Cancer Cell: telomere stress potentiates STING-dependent anti-tumour immunity","url":"https://doi.org/10.1016/j.ccell.2020.05.020"},{"label":"NCI Thesaurus C1350","url":"https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1350"},{"label":"ClinicalTrials.gov: NCT05208944 (THIO-101)","url":"https://clinicaltrials.gov/study/NCT05208944"},{"label":"ClinicalTrials.gov: NCT06908304 (phase 3)","url":"https://clinicaltrials.gov/study/NCT06908304"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["tert"],"drugs":["cemiplimab"],"companies":["maia-biotechnology"],"institutions":[],"pathways":["telomere-maintenance"],"terms":[],"trials":["nct05208944","nct06908304"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"small molecule (nucleoside analogue)","mechanism":"A telomerase substrate precursor: 6-thio-2'-deoxyguanosine is recognised by telomerase and incorporated into newly synthesised telomeres, causing telomere dysfunction in telomerase-positive cells; MAIA sequences it before a PD-1 inhibitor on the basis that telomere stress increases innate sensing and anti-tumour immunity.","approvals":[],"mechanismSteps":["Ateganosine is taken up and converted to its triphosphate","Telomerase, active in most cancers, adds it to the ends of chromosomes","The modified telomeres lose their protective cap and the cell is damaged","The damage alerts the immune system, and a PD-1 inhibitor given afterwards is meant to strengthen that response"],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/ateganosine/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"tert","kind":"target","name":"TERT","route":"/targets/tert/"}],"drug":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}],"company":[{"id":"maia-biotechnology","kind":"company","name":"Maia Biotechnology","route":"/companies/maia-biotechnology/"}],"pathway":[{"id":"telomere-maintenance","kind":"pathway","name":"Telomere maintenance & replicative immortality","route":"/pathways/telomere-maintenance/"}],"trial":[{"id":"nct06908304","kind":"trial","name":"A Phase III Study With THIO + Cemiplimab vs Chemotherapy as 3rd Line Treatment in Advanced/Metastatic NSCLC","route":"/trials/nct06908304/"},{"id":"nct05208944","kind":"trial","name":"THIO Sequenced With Cemiplimab in Advanced NSCLC","route":"/trials/nct05208944/"}]}}