|[April 10, 2014]
Genkyotex's GKT137831 Found to Reverse Fibrosis and Improve Survival in a Model of Persistent Lung Fibrosis
GENEVA & ARCHAMPS, France --(Business Wire)--
Genkyotex, the leading developer of selective NOX enzyme inhibitors,
announced today the publication of data showing that GKT137831, a first
in class NOX1 and 4 inhibitor, was able to reverse lung fibrosis
associated with aging in a new model of idiopathic pulmonary fibrosis.
Collaborators led by Professor Victor Thannickal at the University of
Alabama at Birmingham published the results in the April 9, 2014 issue
Translational Medicine. Genkyotex is investigating GKT137831 in
a Phase II trial in patients with diabetic nephropathy, another
progressive fibrotic disease.
The incidence of mortality and morbidity associated with fibrotic
disorders is increasing worldwide, and aging is an important risk
factor. Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive and
fatal lung disease, with no effective treatment or cure. The incidence
of IPF also increases with age and is characterized by clusters of
myofibroblasts, which cause remodeling and scarring of the alveoli. Data
from these studies show that in contrast to young mice, aged mice
developed irreversible lung fibrosis in response to injury. In aged
mice, myofibroblasts (the key effector cell type and a central mediator
of fibrosis) acquired a senescent phenotype and resistance to the
natural cell death mechanism, apoptosis. These changes were mediated by
NOX4 and could be reversed by genetic or pharmacological inhibition of
"Our results provide preclinical data supporting the potential role for
therapeutic agents that inhibit NOX4 for age-associated fibrotic
disorders and provide new insights into redox mechanisms that control
profibrotic effects of fibroblast senescence," explained Victor J.
Thannickal, MD, Professor of Medicine and Pathology, Director, Division
of Pulmonary, Allergy, and Critical Care, University of Alabama (USA).
"Specifically, we were able to demonstrate that established fibrosis in
lungs of aged mice is partially reversed by administration of GKT137831,
a new NOX inhibitor from Genkyotex."
Details of the Studies
The capacity for fibrosis resolution following bleomycin-induced lung
injury was investigated in young (2 months) and aged (18 months) mice.
Persistent fibrosis in lungs of aged mice was characterized by the
accumulation of senescent and apoptosis-resistant myofibroblasts. These
cellular phenotypes were sustained by alterations in cellular redox
homeostasis resulting from elevated expression of the enzyme NOX4 and an
impaired capacity to induce Nrf2 (NFE2-related factor 2)-mediated
antioxidant responses. Moreover, lung tissue taken from human subjects
with IPF also demonstrated this NOX4-Nrf2 imbalance.
Pharmacological targeting of NOX4 with GKT137831 in aged mice with
established fibrosis attenuated the senescent, antiapoptotic
myofibroblast phenotype and led to a reversal of persistent fibrosis.
Mice treated with GKT137831 also showed improved survival.
"These data confirm previous positive results seen with GKT137831 in a
range of preclinical models of fibrotic diseases in the lung, liver and
kidney," noted Ursula Ney, CEO of Genkyotex. "The role of NOX enzymes in
fibrotic disorders is beginning to be unraveled and we believe our first
in class NOX inhibitors have broad potential in a range of fibrotic
Genkyotex is developing first in class, small molecule therapeutics that
specifically and selectively inhibit the NOX family of enzymes. Using a
unique screening platform, Genkyotex has identified novel NOX inhibitors
with the potential to treat disease areas with a high clinical need and
large market potential. The company's lead product, GKT137831, is now in
a Phase II clinical study in patients with diabetic nephropathy and has
shown promise in several other disease models, including
atherosclerosis, liver fibrosis, osteoporosis, and angiogenesis.
Genkyotex was founded in 2006 by scientists from Switzerland, the USA
and Japan, with backing from Geneva incubator Eclosion. Leading global
investors Edmond de Rothschild Investment Partners, Vesalius BioCapital
and MP Healthcare Venture Management have joined Eclosion in providing
significant investment to Genkyotex. Further information can be found
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