FDA Clears US Enrollment for Ateganosine Phase 2 NSCLC Trial Expansion

The FDA has cleared an amended investigational new drug (IND) application for ateganosine (THIO), enabling MAIA Biotechnology, Inc to open enrollment at US clinical sites for the expansion of its ongoing phase 2 THIO-101 trial (NCT05208944) in patients with advanced non–small cell lung cancer (NSCLC).¹ The clearance also incorporates updated manufacturing protocols, including new manufacturers, revised formulation parameters, and updated storage conditions for the investigational compound.

The THIO-101 trial is a multicenter, open-label, dose-finding phase 2 study evaluating ateganosine sequenced with the PD-1 inhibitor cemiplimab (Libtayo) in patients with advanced NSCLC who have progressed on or become resistant to prior checkpoint inhibitor (CPI)-containing regimens. The current expansion—parts C and D—focuses specifically on third-line (3L) therapy, enrolling patients who have exhausted both prior CPI treatment and chemotherapy. The trial is currently active at 44 clinical sites across 6 countries, and MAIA has identified up to 5 planned US sites for the expansion phase, with the first now activated at Summit Medical Group in New Jersey.

Third-Line NSCLC: A Substantially Unmet Clinical Need

The 3L NSCLC setting represents one of the more challenging treatment contexts in thoracic oncology. Patients in this population have typically progressed on platinum-based chemotherapy and a PD-(L)1 inhibitor, leaving few evidence-based options with meaningful survival benefit. Median overall survival in the 3L setting generally ranges from approximately 5 to 9 months depending on prior treatment history and histology.² The limited efficacy of available salvage regimens, combined with cumulative treatment toxicities, underscores the clinical rationale for investigating agents with novel mechanisms of action.

Ateganosine is a modified nucleotide (6-thio-2'-deoxyguanosine) that functions through a dual mechanism: telomere targeting and immunogenic priming.¹ The compound is incorporated into newly synthesized telomeric DNA by telomerase-expressing cancer cells, inducing telomeric DNA damage, activation of DNA damage response pathways, and selective cancer cell death. Ateganosine-damaged telomeric fragments subsequently accumulate in cytosolic micronuclei, triggering both innate immune activation via the cGAS/STING pathway and adaptive T-cell responses. Preclinical data have demonstrated that sequential treatment with ateganosine followed by PD-(L)1 inhibition produced durable tumor regression across multiple cancer models, with evidence of cancer type-specific immune memory.

Early Efficacy Signals From THIO-101 Parts A and B

Results from earlier cohorts of THIO-101 have informed the expansion design. Among 8 patients treated with ateganosine in parts A and B of the trial, the company reports overall survival (OS) exceeding 2 years in that subgroup. While these data represent a small and heavily pretreated population, the durability of the OS signal is notable in a setting where long-term survival is uncommon.

Vlad Vitoc, MD, founder and CEO of MAIA Biotechnology, noted the clinical significance of this early data in the context of the expansion: "To date, data has shown overall survival beyond two years for eight patients treated with ateganosine in [p]arts A and B of THIO-101. We believe this bodes well for [p]arts C and D evaluations which are specific to [3L] treatment care only, where the unmet need for improved clinical outcomes is most urgent."

The primary end point for the expansion cohorts is overall response rate (ORR) in 3L NSCLC patients with resistance to prior CPI and chemotherapy. Safety and tolerability of ateganosine as both an anticancer compound and an immune-priming agent constitute secondary objectives. The combination has demonstrated an acceptable safety profile to date in the pretreated population enrolled in earlier trial phases.

Regulatory Context: Fast Track Designation and Accelerated Approval Pathway

In July 2025, the FDA granted fast track designation to ateganosine for the treatment of NSCLC.³ This designation, intended for serious conditions where preliminary evidence suggests the drug may demonstrate substantial improvement over available therapies, provides for more frequent interactions with the FDA, eligibility for rolling review, and potential qualification for accelerated approval and priority review.

The amended IND clearance, which incorporated updated efficacy data and revised manufacturing information, is positioned by MAIA as a step that may support a future accelerated approval filing. Accelerated approval under 21 CFR 601.41 allows approval based on a surrogate or intermediate clinical end point, such as ORR, that is reasonably likely to predict clinical benefit, with confirmatory trial data required post approval.⁴

Pivotal Phase 3 Trial Also Underway

In parallel with THIO-101, MAIA is actively screening and enrolling patients for THIO-104, a pivotal phase 3 clinical trial designed to assess OS for ateganosine sequenced with a CPI compared with investigator's choice of chemotherapy. The trial employs a 1:1 randomization and targets enrollment of up to 300 patients with 3L NSCLC. OS as a primary end point would address the confirmatory requirement for any future accelerated approval granted on the basis of ORR.

The dual-trial approach reflects a regulatory strategy that aligns with the FDA's stated framework for expedited development programs in oncology.

REFERENCES

1. MAIA Biotechnology Receives FDA Clearance to Open U.S. Enrollment in Ongoing Phase 2 THIO-101 Trial Expansion. News release. MAIA Biotechnology. June 3, 2026. Accessed June 4, 2026. https://tinyurl.com/5n92f94j

2. Reck M, Rabe KF. Precision diagnosis and treatment for advanced non-small-cell lung cancer. N Engl J Med. 2017;377(9):849-861. doi:10.1056/NEJMra1703413

3. MAIA Biotechnology Receives FDA’s Fast Track Designation for Ateganosine as a Treatment for Non-Small Cell Lung Cancer. News release. MAIA Biotechnology. July 28, 2025. Accessed June 4, 2026. https://tinyurl.com/58nzpra5

4. Accelerated approval program. US Food and Drug Administration. Accessed June 4, 2026. https://tinyurl.com/4debzry6