CHICAGO--(BUSINESS WIRE)--MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on development of first-in-class drugs, announced today that encouraging preclinical results supporting newly-identified immunogenic effects of the company’s lead product candidate, investigational THIO (6-thio-dG), the only telomere-by-telomerase targeting agent in development for the treatment of cancer, has been published in Cancer Cell, a renowned peer-reviewed scientific journal covering major advances in cancer research. The manuscript entitled: “Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity,” Mender et al., is now featured online and will also be published in the September 2020 edition of Cancer Cell, Volume 38, pages 1-12.
Telomerase is the enzyme responsible for the maintenance of telomeres. While inactive in most normal cells, telomerase is activated in the majority of cancer cells, making it an attractive target for cancer therapy. Preclinical data have demonstrated that THIO kills cancer cells by targeting and uncapping telomeres thereby inducing DNA damage. The latest preclinical data showed this is complemented by an immunogenic effect, which may allow for more durable outcomes when used sequentially with immunotherapy. THIO’s activity was shown to be cancer-specific in tumor types with active telomerase. Since up to 35 million patients have telomerase-positive cancers, MAIA Biotech believes these results suggest that THIO holds significant potential to treat large patient populations across many types of cancers.
In these preclinical studies published in Cancer Cell, investigators demonstrated that THIO leads to tumor regression through induction of innate and adaptive host immune system responses. THIO was shown to be directly incorporated into telomeres by telomerase, where it rapidly induced telomeric DNA damage responses, which is selective to telomerase-positive TERT(+) cancer cells without affecting normal telomerase-silent cells. The findings also indicated that THIO induces DNA-mediated innate sensing and activation of immune responses in a host cGAS/STING-dependent manner, leading to improved anti-tumor efficacy. Low doses of THIO, followed by anti-PD-L1 therapy, completely eliminated advanced tumors in preclinical models and produced cancer cell specific immune memory where the immune system continued to be active against the cancer cells after extended periods of time with no additional treatment. These results are significant as they demonstrate how the THIO-produced telomere stress increases innate sensing and adaptive anti-tumor immunity, which provides a strong rationale for sequentially combining telomere-targeted therapy with immunotherapy.
“We believe THIO has the potential to transform the immuno-oncology landscape and change the cancer treatment paradigm, and these most recent findings provide a strong rationale for combining telomere-targeted therapy with immunotherapy,” stated Vlad Vitoc, MD, MAIA’s Chief Executive Officer and President. “We believe the publication of these unprecedented immunogenic effects of THIO in Cancer Cell provides additional validation for this innovative program. We are highly encouraged by these promising findings of tumor elimination, cancer specific immune responses, and stimulation of immune memory, which build upon prior positive preclinical results. These findings provide further support for the company’s plans to advance THIO into Phase 1 clinical studies in 2021.”
THIO (6-thio-dG) is a small molecule in preclinical development and is the only telomere-by-telomerase targeting agent currently in development. THIO is designed to selectively kill cancer cells by modifying telomeric DNA structure and function utilizing telomerase. Telomerase is present in >85% of human cancers and contributes significantly to proliferation and immortality of cancer cells. THIO is recognized by telomerase and incorporated into telomeres selectively in cancer cells. Once incorporated, it compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell death. In preclinical studies, this rapid cancer cell death occurred without impacting normal cells. THIO is investigational and has not been approved for any use anywhere in the world.
About Cancer Cell
Cancer Cell provides a high-profile forum to promote major advances in cancer research and oncology. The primary criterion for considering manuscripts is whether the studies provide major advances into answering important questions relevant to naturally occurring cancers. Cancer Cell is also interested in publishing clinical investigations, in particular those that lead to establishing new paradigms in the treatment, diagnosis, or prevention of cancers; those that provide important insights into cancer biology beyond what has been revealed by preclinical studies; and those that are mechanism-based proof-of-principle clinical studies. For more information, please visit www.cell.com/cancer-cell or follow the journal on Twitter: @Cancer_Cell.
About MAIA Biotechnology, Inc.
MAIA Biotechnology, Inc. is a targeted therapy, immuno-oncology company focused on development of first-in-class drugs with novel mechanisms of action that are intended to meaningfully improve and extend the lives of people with cancer. MAIA’s business model involves placing drug candidates in their own dedicated, R&D focused subsidiary company, which is supported by the common infrastructure, management team, and resources of the MAIA enterprise. This model allows MAIA to provide more focused R&D support to each drug candidate, while also distributing shared central resources among subsidiary companies to maintain a lean, capital-efficient operating structure. Drug candidates include (i) THIO, a telomere-by-telomerase targeting agent in preclinical development for the treatment of telomerase positive cancer cells; (ii) GMC1, a FKBP52 co-chaperone-inhibitor being evaluated for prostate cancer and breast cancer; and (iii) MJC13 is a drug candidate with a potentially novel mode of action targeting androgen receptor (AR) inhibition that is important in prostate and breast cancers. MAIA is led by a passionate, principled and highly experienced management team with significant drug development experience, committed to advancing promising agents into clinical trials. For more information, please visit www.maiabiotech.com.
Forward Looking Statements
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