FibroStatin Announces Breakthrough in the Fight Against Drug-Resistant Cancer and Fibrosis. Novel Treatment Inhibits the Epithelial-Mesenchymal Transition (EMT), a Key Underlying Pathology Contributing to These Diseases.

RALEIGH, N.C., Aug. 3, 2016 /PRNewswire/ -- FibroStatin (www.fibrostatin.com) announces the development of a breakthrough treatment to inhibit the epithelial-mesenchymal transition (EMT), a fundamental underlying pathology active in drug-resistant invasive cancer and organ fibrosis.   EMT is regarded as a very important but difficult process to target therapeutically.

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The Company's lead treatment candidate, designated T12, targets the extracellular GPBP kinase that regulates the assembly of a previously unrecognized mesenchymal collagen IV network.  This extracellular network mediates and stabilizes many of the cellular phenotypic changes that occur during EMT.  In animal models of idiopathic pulmonary fibrosis, treatment with T12 significantly reduced fibrosis and extended survival.  T12 treatment was also effective in slowing the growth and spread of tumors (lung and breast) in animal studies.  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.

Epithelial-Mesenchymal Transition (EMT)

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.  EMT is an essential cellular process that occurs during tissue development and wound healing, but is also activated under pathological conditions and significantly contributes to drug resistant metastatic cancer and organ fibrosis.

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.  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.  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 is a fundamental cause of the emergence of drug resistant tumors and their spread throughout the body.

Discovery of GPBP, the mesenchymal collagen IV network, and T12

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.  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.

FibroStatin scientists have recently discovered that GPBP regulates the formation of a novel previously unrecognized collagen IV mesh-like network that mediates cellular phenotypic changes during EMT and stabilizes the formed mesenchymal phenotype.

Pathological conditions that induce EMT also induce the upregulation of GPBP and collagen IV, indicating a causal relationship between the two.  Upregulated GPBP forms highly active pathogenic oligomers which induce a change in GPBP function that 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.

T12 is a small molecule inhibitor that was designed to selectively inhibit the formation of pathogenic GPBP oligomers, and in so doing inhibits mesenchymal collagen IV assembly.  This action inhibits EMT and also destabilizes formed pathogenic mesenchymal cells leading to cell death or cell phenotype reversion.

T12 shows little or no inhibitory activity toward other kinases, and exhibits low toxicity in cell assays and in dose escalation animal toxicity studies completed to date.  And as mentioned above, T12 has produced large treatment effects in animal models of lung and breast cancer, as well as fibrosis.

About FibroStatin

FibroStatin is a developmental stage biotechnology company developing proprietary treatments for organ fibrosis and drug-resistant cancer using its proprietary GPBP and collagen IV technologies.  The Company's R&D operations are located in the Scientific Park of the University of Valencia, Valencia, Spain.  Financing and business development are run through a fully owned subsidiary located in Raleigh, North Carolina, USA.  FibroStatin plans is to advance its treatment candidates through clinical trials in collaboration with corporate partners.

CONTACT:                                                                                                                             
J. Wesley Fox III, Ph.D.
President and CEO
Email
(919) 349-4954

SOURCE FibroStatin