FibroStatin’s T12 ready to deliver TKO?

Lead candidate proves effective in fight vs. drug-resistant invasive cancer, organ fibrosis

Lori Lesko
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RALEIGH, N.C.—After searching the past 10 years for a high-powered weapon to ultimately defeat cancer, biotech FibroStatin has identified lead candidate T12 as a potentially breakthrough treatment to inhibit epithelial-mesenchymal transition (EMT), a fundamental underlying pathology active in drug-resistant invasive cancer and organ fibrosis. The T12 discovery is especially impressive since EMT is regarded as an important—but difficult—process to target therapeutically.
Headquartered in Valencia, Spain, with its financing and business division based in Raleigh, N.C., FibroStatin believes it is on to something with T12 since none of the currently approved treatments for lung fibrosis and lung cancer target EMT, and none target the microenvironment that stabilizes the drug-resistant and invasive mesenchymal phenotype, the company says.
J. Wesley Fox III, president and CEO of FibroStatin’s U.S. division, did not respond to requests from DDNews for a comment.
A company press release explains that EMT is a process whereby epithelial cells lose their characteristic polarity and cell-cell adhesion properties, and gain migratory and invasive properties, becoming mesenchymal cells with multipotent capabilities able to differentiate into a variety of cell types.
Founded in 2005, FibroStatin is a developmental-stage biotechnology company that has developed a strategy that has allowed patenting of new compounds and diagnostic tools to detect and intervene in GPBP (Goodpasture antigen-binding protein), a new marker and therapeutic target relevant to autoimmunity and cancer.
FibroStatin researchers report that when working on animal models with idiopathic pulmonary fibrosis, treatment with T12 “significantly reduced fibrosis and at the same time extended survival. T12 treatment was also effective in slowing the growth and spread of lung and breast tumors in animal studies.”
An essential cellular process that occurs during tissue development and wound healing, EMT is “also activated under pathological conditions and significantly contributes to drug-resistant metastatic cancer and organ fibrosis,” the company says.
“Smoking, air pollution, toxic drugs and autoimmune disease can all initiate pathogenic EMT, leading to the emergence of pluripotent mesenchymal lung cells that form myofibroblasts, which synthesize collagen I and lay down scar tissue,” FibroStatin says. “In this manner, EMT is a significant contributor to lung fibrosis.”
In the case of lung cancer, “some tumor cells treated with chemotherapies undergo EMT, which produces mesenchymal tumor cells,” the company says. “These tumor cells replicate slowly, are resistant to chemotherapies and exhibit invasive behavior resulting in drug-resistant tumor cells migrating to distant tissues forming metastases. EMT also is a fundamental cause of the emergence of drug resistant tumors and their spread throughout the body.”
The extracellular microenvironment and its coordinated binding interactions with neighboring cells are “well-established mediators of cellular phenotype, and an obvious place to search for new therapeutic strategies to impact pathogenic EMT,” FibroStatin notes. “However, the difficulty in studying the complex and largely insoluble extracellular matrix has made it difficult to identify therapeutic approaches and viable targets.”
FibroStatin’s scientists previously discovered an extracellular kinase termed GPBP that targets collagen IV, “an important component of sheet-like extracellular structures called basement membranes, which function to separate specialized cell function and mediate and stabilize a cell’s phenotype by establishing numerous matrix-cell binding interactions.”
Pathological conditions that induce EMT also induce the upregulation of GPBP and collagen IV, indicating a causal relationship between the two, the company says. Upregulated GPBP forms highly active pathogenic oligomers that induce a change in GPBP function, which in turn cause (1) a disruption of the sheet-like collagen IV network within basement membranes and (2) a subsequent organization of a distinct mesenchymal mesh-like collagen IV network surrounding and stabilizing the formed mesenchymal cells.
FibroStatin’s objective is to advance T12 into clinical studies, up to and including Phase 2a studies, with the objective of demonstrating safety and biological activity in slowing the growth and spread of lung cancer.
None of the currently approved treatments for lung cancer target the epithelial-to-mesenchymal transition of the tumor, FibroStatin says. T12 has exhibited a robust treatment effect and low toxicity in animal studies.
T12 “has displayed preferential efficacy on mesenchymal lung and breast cancer models,” the company says. T12 is “expected to exhibit synergistic anti-cancer activity when combined with cytotoxic agents and delay the emergence of recurrent cancer and drug resistance. T12 is also expected to reduce metastasis formation from tumors that no longer respond to therapies.”

Lori Lesko

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