Tvardi Therapeutics (“Tvardi”), a privately held, clinical-stage biopharmaceutical company focused on the development of STAT3 inhibitors, announced the publication of preclinical studies establishing that its lead compound, TTI-101, is effective against treatment-resistant breast cancers. The paper, published in Clinical Cancer Research, elucidated the STAT3 pathway as the mechanism of resistance and demonstrated that TTI-101 overcame this resistance in hormone receptor-positive (ER-positive), HER2-negative, palbociclib-resistant breast cancers. Palbociclib (a cyclin-dependent kinase (CDK) 4/6 inhibitor) in combination with endocrine therapy is the standard of care treatment for ER-positive, HER2-negative breast cancers.
The study, conducted by investigators at The University of Texas MD Anderson Cancer Center, demonstrated that TTI-101 alone induced cell death among palbociclib-resistant cell lines, by reducing activated STAT3. In addition, TTI-101 and various combinations of PARP inhibitors were synergistically effective in palbociclib-resistant cell lines. The study also demonstrated that, similar to the tested cell lines, archived breast tumors of patients who progressed on endocrine and palbociclib treatment express activated STAT3 suggesting TTI-101 as a promising therapeutic option for this patient population.
“ER-positive, HER2-negative breast cancers that develop resistance and metastasize represent the greatest proportion of breast cancer deaths. However, many patients develop resistance to standard of care CDK4/6-based therapy leaving them with little-to-no therapeutic options. The work in this paper is pivotal not only in understanding the targeted mechanisms of resistance to CDK4/6 inhibition but also in evaluating TTI-101, a STAT3 inhibitor, that can specifically and effectively target the CDK4/6 resistant cells, providing a compelling therapeutic approach,” said Khandan Keyomarsi, PhD, senior author and Professor of Experimental Radiation Oncology at MD Anderson Cancer Center.
“Dr. Keyomarsi’s work further validates STAT3 is an incredibly important target in a broad range of tumors including breast cancer,” shared Imran Alibhai, PhD, CEO of Tvardi. “This preclinical data is consistent with the clinical activity across a variety tumors we are seeing in our ongoing Phase 1 trial of TTI-101 in advanced solid tumors. We are quite encouraged by these results.”
To access the published paper please visit the Clinical Cancer Research website.
For more information about the ongoing trial of TTI-101 being conducted at MD Anderson, please visit ClinicalTrials.gov (NCT03195699).
TTI-101 is an orally delivered small-molecule that directly binds and subsequently blocks the activation of the STAT3 protein, which is a central mediator of cancer, chronic inflammation, and fibrosis. Inhibition of STAT3 in cancer has been shown to inhibit tumorigenesis as well as reverse immunosuppression within the tumor microenvironment. TTI-101 is currently being studied at MD Anderson Cancer Center in a first-in-man Phase 1 trial of patients with advanced solid tumors who have failed all lines of therapy.
About Tvardi Therapeutics
Tvardi is a privately held, clinical-stage biopharmaceutical company developing small molecule inhibitors of STAT3. STAT3 is a key regulatory protein positioned at the intersection of many signaling pathways integral to the survival and immune evasion of cancer cells as well as to the pathogenesis of many inflammatory and fibrotic diseases. STAT3 has long been recognized as a prime target for oncology as it has a dual mechanism in promoting the growth of tumors. Early clinical studies have shown that the company’s lead asset in cancer, TTI-101, is well tolerated and has clinical activity. To learn more, visit www.tvardi.com