FDA Grants Orphan Drug Designation to THIO in Small Cell Lung Cancer

Pipeline Report: August 2022

The FDA has granted an orphan drug designation to THIO for the treatment of patients with small cell lung cancer.



The FDA has granted an orphan drug designation to THIO (6-thio-dG, 6-thio-2’-deoxyguanosine) for the treatment of patients with small cell lung cancer (SCLC), according to an announcement from MAIA Biotechnology.1

THIO is a potentially first-in-class telomere targeting agent. Telomeres, along with the enzyme telomerase, which is present in more than 85% of human cancers,2 play a key role in cancer cell growth and their resistance to current treatments. The agent acts through recognition of telomerase, allowing its entrance into telomeres in cancer cells. Once inside, THIO inhibits the telomere structure and function, causing uncapping of the chromosome ends and cell death.

“Patients with SCLC have exceptionally poor prognosis, with only 6% of patients remaining alive five years after diagnosis,” Mihail Obrocea, MD, chief medical officer of MAIA, stated in a press release. “While clinical progress in SCLC treatment has been incredibly slow to evolve, an increased understanding of the disease biology has demonstrated that targeted therapies, like THIO, may offer a novel therapeutic option for SCLC.”

In April 2022, the FDA granted THIO its first orphan drug designation for the treatment of patients with hepatocellular carcinoma (HCC).3

“Receiving our second orphan drug designation is an impressive regulatory milestone that highlights the FDA’s recognition of THIO’s potential to improve outcomes for patients with SCLC and HCC,” Vlad Vitoc, MD, MAIA’s chairman and chief executive officer of MAIA, stated in a press release. “We believe there is a significant, multi-billion-dollar opportunity for THIO across many difficult-to-treat cancers, and we look forward to advancing THIO towards the market and to patients in need for more effective therapies.”

Prior research has shown that low doses of THIO, followed by anti–PD-L1 or anti–PD-1 therapy, eradicated advanced tumors in preclinical models in vivo and produced cancer cell–specific immune memory, allowing the immune system to be active against the cancer cells after treatment cessation.

As such, THIO is being developed as a second- or later-line treatment for patients with non–small cell lung cancer (NSCLC) that have progressed on standard-of-care checkpoint inhibitors.

The multicenter, open-label, dose-finding phase 2 trial (NCT05208944), which opened on June 8, 2022, is evaluating the combination of THIO and cemiplimab-rwlc (Libtayo) in patients with NSCLC who progressed or relapsed after treatment with an immune checkpoint inhibitor.4

The rationale for the study stems from the hypothesis that treatment with THIO prior to cemiplimab would restore tumor responses to immunotherapy in patients who developed resistance or relapsed after receiving first-line treatment with an immune checkpoint inhibitor.

“There is significant room for improvement in the treatment landscape for SCLC, with the currently available standard-of-care therapies providing incremental benefit to patients. We are optimistic about our telomere-targeting approach to provide clinical benefit in patients with SCLC, CRC [colorectal cancer] and HCC who have failed first-line therapies, and we look forward to evaluating our approach in a future trial,” Sergei Gryaznov, PhD, chief scientific officer of MAIA, concluded.


  1. MAIA Biotechnology receives FDA orphan drug designation for THIO for the treatment of small-cell lung cancer (SCLC). News release. MAIA Biotechnology. August 2, 2022. Accessed August 9, 2022. https://bit.ly/3QydrVo
  2. THIO first-in-class cancer telomere targeting agent. MAIA Biotechnology. Accessed August 9, 2022. https://maiabiotech.com/pipeline/thio/
  3. MAIA Biotechnology, Inc. announces FDA orphan drug designation THIO for the treatment of hepatocellular carcinoma (HCC). News release. MAIA Biotechnology. April 26, 2022. Accessed August 9, 2022. https://bwnews.pr/3bIAm1M
  4. THIO sequenced with cemiplimab in advanced NSCLC. ClinicalTrials.gov. Updated July 8, 2022. Accessed August 9, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05208944
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