Segue Therapeutics drug development pipeline
Pancreatic cancer and fibrosis
ST2001 is our lead drug and is a member of the cardiac glycoside group. This drug prevents the TGF-ß mediated differentiation of fibroblasts into cancer associated fibroblasts (CAFs). In turn, CAFs stimulate tumor cell proliferation, survival, invasion and resistance to chemotherapy drugs.
"Activated" fibroblasts also are important in the progression of fibrotic diseases that impact vital organs in the body, including the kidneys, liver and lungs. Idiopathic pulmonary fibrosis (IPF) kills 40,000 Americans each year and more effective treatments are needed.
The ST2000 series of drugs also contains other classes of drugs that prevent activation of fibroblasts by novel mechanisms of action to be determined. We have determined that combinations of ST2001 and ST2022 are more effective than either drug alone and more effective than FDA approved drugs to treat fibrosis.
The ST1000 series of drugs block the outward movement of lysosomes in tumor cells in response to cues in the tumor microenvironment. Peripherally localized lysosomes secrete proteases which stimulates tumor invasion. Using high content imaging screens we discovered drugs that block outward movement of lysosomes and tumor invasion. If fact, using a genetic approach to “lock” lysosomes near the nucleus completely block the formation of tumors in mouse models. We predict these drugs will be effective in combination with fibrosis inhibitors and will be particularly effective in treatment of cancers, such as brain cancer, where invasion leads to mortality.