MAIA Biotechnology, Inc. and BeiGene have entered into a clinical supply agreement to evaluate the efficacy of MAIA's THIO, a small molecule telomere-targeting anticancer agent, in combination with BeiGene’s immune checkpoint inhibitor (CPI) tislelizumab. The collaboration will focus on three cancer indications: hepatocellular carcinoma (HCC), small cell lung cancer (SCLC), and colorectal cancer (CRC).
The single-arm, pivotal Phase 2 trials will study the drug combination in patients with HCC, SCLC, and CRC. Preclinical results of THIO in combination with a CPI demonstrated complete, durable, and highly potent anti-tumor immune responses in HCC models. In SCLC models, THIO treatment showed profound activation of innate and adaptive anti-tumor responses. CRC pre-clinical studies showed that THIO administered in sequence with a CPI resulted in 100% complete response, inducing anticancer immune memory with no recurrence after rechallenge with 10x more CRC cells and no additional therapy. Across all preclinical studies, THIO converted immunologically cold and non-responsive tumors into hot tumors that respond to a CPI.
THIO's Orphan Drug Designations
"Based on excellent pre-clinical results, THIO was awarded orphan drug designation (ODD) for the treatment of both HCC and SCLC. Along with a third ODD in glioblastoma, the FDA has clearly recognized THIO’s potential as an effective treatment for multiple cancer indications. Comparatively, most oncology compounds at this stage of development have only one indication," said MAIA Chairman and Chief Executive Officer Vlad Vitoc, M.D.
Collaboration Terms and Future Development
Under the terms of the collaboration, MAIA will sponsor and fund the planned clinical trials, while BeiGene will provide tislelizumab. MAIA maintains global development and commercial rights to THIO and is free to develop the programs in combination with other agents and in other indications. MAIA is targeting accelerated FDA approvals in each of the three indications to be studied, along with non-small cell lung cancer (NSCLC), the focus of a current Phase 2 clinical trial of THIO with a CPI.
Market Trends and Opportunities
Hepatocellular carcinoma is the third most common cause of cancer-related deaths globally. The market for HCC was valued at $780 million in 2023 and is expected to grow at a CAGR of 6.3% to $1.5 million by 2034. Small cell lung cancer accounts for an estimated 15% of all lung cancer globally. The global SCLC therapeutics market is valued at approximately $6.5 billion in 2024 and is expanding at an estimated CAGR of 12.3% from 2024 to 2034. Colorectal cancer is the second leading cause of cancer-related deaths globally. Approximately 85% of all CRC cases are classified as microsatellite stable, and MSS tumors are "cold tumors" that typically do not trigger the body’s immune system. The global CRC therapeutics market size was $9.26 billion in 2018 and is projected to reach $26.49 billion by 2032.
About THIO
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.
