MAIA Biotechnology, Inc. is set to present preclinical data on its novel telomere-targeting THIO prodrugs at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, from October 23-25, 2024. The presentation will highlight the efficacy of MAIA's second-generation THIO-based prodrugs, MAIA-2021-20 and MAIA-2022-12, in overcoming immunotherapy resistance and inhibiting tumor growth in various cancer models.
These lipid-conjugated compounds, classified as telomere-targeting divalent dinucleotides, represent a new chemical class designed to selectively target and disrupt telomere function in cancer cells. Telomeres, essential for cancer cell survival and resistance to therapies, are the focus of these innovative agents.
Preclinical Efficacy
Preclinical studies evaluated the efficacy of MAIA-2021-20 and MAIA-2022-12, both alone and in combination with anti-PD-L1 immune checkpoint inhibitors. The results indicated that treatment with each prodrug was highly efficacious, demonstrating the ability to overcome immunotherapy resistance, a significant challenge in cancer treatment.
According to MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D., the studies showed "marked activity in advanced tumors and resulted in tumor growth inhibition in preclinical models of lung cancer, colorectal carcinoma, melanoma and hepatocellular carcinoma." These findings suggest a broad potential application of the THIO prodrugs across various cancer types.
THIO Mechanism of Action
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational agent that targets telomeres. By inducing telomerase-dependent telomeric DNA modification, THIO triggers DNA damage responses and selective cancer cell death. The accumulation of THIO-damaged telomeric fragments in cytosolic micronuclei activates both innate (cGAS/STING) and adaptive (T-cell) immune responses.
Previous research indicates that sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in significant and sustained tumor regression in advanced, in vivo cancer models by inducing cancer type–specific immune memory. THIO is currently being developed as a second or later line of treatment for NSCLC patients who have progressed beyond standard-of-care checkpoint inhibitors.
Presentation Details
The poster presentation, titled "New Dual-Pharmacophore Dinucleotide Prodrugs as Potent Telomere Targeting Anticancer Molecules" (Abstract number: ENA24-0044), will take place on Wednesday, October 23, 2024, at noon CEST. Ilgen Mender, Ph.D., Director of Biology Research at MAIA Biotechnology, will present the findings. The poster will be accessible on MAIA’s website following the presentation.
MAIA Biotechnology has designed and evaluated over 80 THIO-like compounds and has filed three U.S. patent applications for its second-generation telomere-targeting agents, underscoring its commitment to advancing innovative cancer therapies.
