Agennix, Inc. announced today that it
has initiated a randomized, double-blind, placebo-controlled Phase 2 study
of oral talactoferrin alfa in patients with severe sepsis. This is the
first clinical trial of talactoferrin in sepsis and is based on both the
mechanism of action of talactoferrin, and promising preclinical data
demonstrating a significant reduction in mortality by talactoferrin in a
variety of animal models of sepsis, including some that cause 100%
mortality in untreated animals. The Phase 2 trial, which has started
enrollment, will be conducted at approximately 25 leading U.S. centers with
investigators who are very experienced in conducting trials in severe
sepsis.
The study is being supported by a Small Business Innovative Research
(SBIR) grant awarded from the National Institutes of Health (NIH). The
total amount of the grant, $3 million, will provide the financial resources
necessary to conduct the 190-patient study, which is designed to evaluate
the safety and activity of talactoferrin in patients with severe sepsis.
Results from the trial are anticipated in mid-2009.
"The number of sepsis-related deaths is on the rise, in spite of
available treatment options," said Kalpalatha K. Guntupalli, M.D.,
Professor of Medicine, Chief of Pulmonary, Critical Care, and Sleep
Medicine at Baylor College of Medicine and the Principal Investigator for
the Phase 2 study. "Talactoferrin is a very promising compound with broad
immunomodulatory and anti-inflammatory properties. The preclinical data in
sepsis are very exciting, with talactoferrin demonstrating reductions in
mortality rates of 50 percent or more in various animal models. We hope
that the preclinical results translate to the drug showing activity in the
Phase 2 study by reducing the number of deaths in patients with severe
sepsis."
Sepsis is a clinical syndrome defined by the presence of known or
suspected infection and associated inflammatory response. Multi-organ
damage from high levels of circulating cytokines originating from the gut
is an important contributor to sepsis-induced morbidity and mortality.
Talactoferrin modulates these gut-induced cytokine surges through its
effects on the Gut Associated Lymphoid Tissue (GALT). In preclinical
experiments, oral talactoferrin significantly reduced mortality from
endotoxin- and bacterially-induced sepsis, as well as the systemic cytokine
surge induced by endotoxin.
"Severe sepsis is a serious medical condition that is associated with
the failure of one or more organ systems, such as cardiovascular or
respiratory," said Mitchell M. Levy, M.D., Professor of Medicine, Brown
Medical School, Medical Director, Medical Intensive Care Unit, Rhode Island
Hospital, and an Investigator in the study. "New therapies for this disease
are desperately needed. Talactoferrin is particularly exciting because of
its unique mechanism of action mediated through its effect on the
gastrointestinal tract and the GALT, and its potential to impact many of
the abnormal pathways that contribute to sepsis-induced organ damage and
associated morbidity and mortality."
About the SBIR Grant
The Small Business Innovation Research (SBIR) program of the National
Institutes of Health is a set-aside program (2.5% of an agency's extramural
budget) for supporting domestic small business concerns to engage in
Research or Research and Development in areas that have the potential for
commercialization. Some of the objectives of the SBIR Program include using
small businesses to stimulate technological innovation, strengthening the
role of small business in meeting Federal Research or Research and
Development needs, and increasing private sector commercialization of
innovations developed through Federal SBIR Research and Development
funding.
"The SBIR grant for sepsis, with its $3 million budget, will allow us
to conduct the study with enough patients to provide an answer regarding
talactoferrin's activity in the clinical setting," said Robert Lodato,
M.D., Associate Professor of Medicine, University of Texas Health Science
Center, and Medical Monitor for the study.
About the Phase 2 Study
The double-blind, placebo-controlled Phase 2 study of talactoferrin
will enroll 190 patients who have a diagnosis of sepsis with at least one
organ dysfunction due to sepsis. Patients will receive standard therapy
(including, at the discretion of the primary physician, drotrecogin alfa
activated, marketed as Xigris(R), and will be randomly assigned (1:1) to
receive either talactoferrin (1.5 g) or placebo three times a day for up to
28 days or until discharge from the intensive care unit (ICU), whichever
occurs first. The primary efficacy endpoint of the trial is 28-day
all-cause mortality. Secondary endpoints include number of ICU days,
shock-free days, incidence and severity of organ failure/dysfunction and
circulating levels of pro- inflammatory cytokines. Safety will be monitored
and patients will be followed for survival at three and six months
post-randomization.
About Sepsis
Sepsis is a clinical syndrome consisting of known or suspected
infection and associated inflammatory response. Severe sepsis is defined as
the presence of sepsis with dysfunction of one or more organs. The
incidence of sepsis in the United States is estimated to be approximately
750,000 cases per year, with an annual increase of approximately 1.5%, and
estimated mortality due to sepsis of 210,000 deaths each year. According to
the Centers for Disease Control and Prevention, sepsis is among the top 10
leading causes of death in the United States.
Treatment for sepsis consists of eradicating the underlying infection
and providing supportive care for any associated organ dysfunction. In
November 2001, FDA approved the first biologic treatment for severe sepsis.
This drug, Xigris(R), is a genetically engineered form of a naturally
occurring human protein, activated Protein C. Despite the availability of
Xigris(R), treatment for severe sepsis remains an area of significant unmet
medical need.
About Talactoferrin Alfa
Talactoferrin, a novel dendritic cell recruiter and activator (DCRA),
is a unique recombinant form of human lactoferrin, an important
immunomodulatory protein. Talactoferrin is an orally administered protein
that mediates its activity through the gut and the GALT - the largest
lymphoid organ in the body.
In 1988, scientists at Baylor College of Medicine, Houston, Texas,
discovered a way to produce this protein in the laboratory, thus paving the
way for testing its potential to help fight serious diseases that cause
enormous suffering worldwide.
Lactoferrin, found in the highest concentration in milk, is expressed
throughout the body in immune cells and on all body surfaces exposed to the
external environment. Lactoferrin plays an important role in helping to
establish the immune system, including the GALT, in infants. Talactoferrin
is produced in Aspergillus niger, a filamentous fungus, and is structurally
identical to native human lactoferrin in all material respects, differing
only in its glycosylation.
About Agennix
Agennix is a private biotechnology company developing a first-in-class
molecule with activity in several types of cancer and in other indications
with unmet medical needs. This molecule, talactoferrin, is a targeted
dendritic cell recruiter and activator with a novel mechanism of action.
Agennix is preparing to initiate Phase 3 trials in two non-small cell lung
cancer indications (talactoferrin in combination with chemotherapy in
previously untreated patients and talactoferrin monotherapy in patients who
have failed two or more previous therapies), a Phase 2b trial in renal cell
cancer, and Phase 2 trials in other indications. Talactoferrin's potential
advantages in non-small cell lung cancer and in other tumor types include
its promising anti-tumor activity, its well tolerated safety profile
including a reduction of some chemotherapy toxicities, its oral route of
administration, and its apparent usefulness in multiple tumor types both as
a single agent and in combination with other drugs. The oral formulation of
talactoferrin is also being developed in severe sepsis and the topical
formulation is being developed in patients with diabetic foot ulcers.
Agennix retains all of the commercial and economic rights to talactoferrin
for all indications worldwide, and has strong global intellectual property
protection for talactoferrin that has been tested and upheld.
More information about Agennix is available on the Company's web site
at agennix.
Xigris is a registered trademark of Eli Lilly and Company
Agennix, Inc.
agennix
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