MAIA Biotechnology reports positive interim Phase 2 THIO‑101 data (NCT05208944), with ateganosine achieving a 90.5% disease control rate in third‑line NSCLC patients resistant to checkpoint inhibitors and chemotherapy.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
MAIA Biotechnology has reported positive interim efficacy data from Part C of its Phase 2 THIO-101 trial (NCT05208944), with the investigational agent ateganosine achieving a 90.5% disease control rate (DCR) in patients with advanced third-line non-small cell lung cancer (NSCLC). While overall response rate (ORR) is the trial’s primary efficacy endpoint, the reported DCR represents an interim measure of clinical activity. The combination regimen, which administers ateganosine before the PD-1 inhibitor cemiplimab (Libtayo®), was evaluated in patients whose disease had progressed after multiple prior therapies, including immune checkpoint inhibitors, chemotherapy, and docetaxel.
Among 21 efficacy-evaluable patients who underwent at least one post-treatment tumor assessment, 19 achieved disease control, corresponding to a 90.5% interim DCR. The company did not disclose the breakdown of responses into complete responses, partial responses, or stable disease. According to MAIA, currently available chemotherapy options in this setting typically achieve disease control rates of approximately 25% to 35%, highlighting the potential clinical activity of the investigational regimen.
Mechanism of Action
Ateganosine (THIO, 6-thio-dG) is a first-in-class investigational telomere-targeting therapy that combines direct cancer cell killing with immune activation. The modified nucleotide selectively incorporates into telomerase-positive cancer cells, triggering telomeric DNA damage and cell death while sparing most normal cells.
The resulting damaged telomeric DNA fragments accumulate in cytosolic micronuclei, activating the cGAS-STING pathway and stimulating both innate and adaptive immune responses. Preclinical studies have shown that sequential administration of ateganosine followed by PD-(L)1 blockade produces durable tumor regression and cancer-specific immune memory, providing the biological rationale for combining the therapy with cemiplimab.
Patients with advanced NSCLC who progress after checkpoint inhibitor therapy and chemotherapy have limited treatment options and generally poor outcomes, underscoring the need for new therapeutic strategies.
Phase 2 THIO-101 Expansion Continues to Show Encouraging Activity
THIO-101 is an open-label, multicenter Phase 2 trial evaluating ateganosine followed by cemiplimab in patients with advanced NSCLC who previously failed checkpoint inhibitor-based treatment. The study investigates whether low-dose ateganosine can prime anti-tumor immunity before PD-1 inhibition.
The trial has two primary objectives: evaluating safety and tolerability while assessing clinical efficacy using overall response rate (ORR) as the primary endpoint. Part C specifically enrolled third-line patients with resistance to prior checkpoint inhibitors and chemotherapy.
MAIA recently completed international enrollment for the Part C expansion cohort. Treatment with ateganosine followed by cemiplimab has shown an acceptable safety profile in this heavily pre-treated population. The company did not report detailed safety findings, including rates of Grade 3 or higher adverse events, in this interim update.
Results Reinforce Earlier Clinical Findings
CEO Vlad Vitoc stated that the latest findings are consistent with results previously reported from Parts A and B of THIO-101, where the combination achieved an 88% disease control rate in third-line NSCLC. He noted that the Part C population had received more extensive prior treatment, with every participant previously exposed to docetaxel in addition to demonstrating resistance to immunotherapy and other chemotherapy regimens.
The consistency of disease control across increasingly refractory patient populations suggests the sequential regimen continues to demonstrate clinical activity despite greater treatment resistance. However, longer follow-up and analysis of the trial’s primary endpoint, overall response rate, will be important to further establish its therapeutic potential.
MAIA is expected to continue evaluating overall response rates and other efficacy endpoints as follow-up from the Phase 2 program progresses. The company recently completed international enrollment in Part C, and additional efficacy and safety analyses are anticipated as more patients complete treatment and assessment.
What it means for patients
Patients with advanced NSCLC whose cancer has progressed after immunotherapy and chemotherapy have limited treatment options. Although ateganosine remains investigational and has not been approved, the interim Phase 2 findings suggest the combination with cemiplimab may help control disease in a heavily pre-treated population. Additional follow-up and confirmation of the trial’s primary endpoint, overall response rate, are needed before the treatment’s clinical benefit can be fully established.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.