Reveals Insights into Potential Reasons for Drug Failures
SAN DIEGO, June 11 /PRNewswire/ -- Entelos, Inc., the leader in
biosimulation technologies for pharmaceutical research and development,
announced today that it presented data from a large quantitative comparison in
an oral session at the 65th Annual American Diabetes Association Meeting.
Comparison of protocols performed in the non-obese diabetic (NOD) mouse model,
the primary animal model used to study type 1 diabetes, to human protocols for
all clinically tested type 1 diabetes therapies led to the discovery that
discrepancies in dosing, formulation, and timing could potentially account for
the failure of many drugs in human clinical trials. Such insights may help
translate preclinical animal data to better understand a drug's potential
safety and efficacy in humans.
"This is the first time that all of these data were brought together and
compared in a unique, insightful manner," said Mikhail Gishizky, Chief
Scientific Officer of Entelos. "Interestingly, some commonly held tenets
regarding treatments in the NOD mouse model were not confirmed; we found that
timing of treatment initiation and duration strongly influence efficacy, and
that protocol discrepancies may have contributed to disappointing human
clinical trial results. This analysis provides a unique perspective on NOD
interventions and suggests that careful consideration and more thorough
testing of treatment timing, duration, and protocol design may improve
clinical translation."
These insights were revealed during the first year of development of the
Type 1 Diabetes PhysioLab(R) platform, which was developed in collaboration
with the American Diabetes Association (ADA). The goals of this Collaboration
are to advance our understanding of type 1 diabetes pathogenesis using
predictive mathematical models, and improve the rationale for advancing
potential therapies from the NOD mouse model into human clinical trials.
Our retrospective analysis revealed that many therapies had been tested at
different stages of disease progression in NOD mice vs. human trials. For
example, azathioprine, bacillus Calmette- Guerin (BCG), pentoxyfilline, and
linomide were tested only in pre-diabetic mice, while corresponding clinical
trials were conducted on diabetic patients. Additionally, NOD mouse studies,
such as insulin tolerization and anti-CD3, indicate that administration dose
and schedule can drastically influence efficacy. Thus, significant differences
in dosing between animal and human trials of insulin, nicotinamide, BCG, and
linomide may have contributed to suboptimal human results. Finally, therapies
such as nicotinamide and oral insulin tested in NOD mice and Bio-breeding (BB)
rats resulted in distinct outcomes, suggesting that sensitivity to
interspecies variations may have hampered translation. Identifying the impact
of dose, time, and species-specific effects on efficacy may be critical to
future clinical success.
About Type 1 Diabetes
Estimates are that as many as one million or more Americans have type 1
diabetes, an immunemediated disease that leads to destruction of the insulin-
producing beta cells in the pancreas and the need for daily insulin injections
throughout life. Type 1 diabetes usually arises in children or young adults.
Scientific understanding of this disease in humans has been limited by the
difficulty of identifying those people likely to develop the disease as well
as practical considerations in studying humans with the condition. At this
time there are no preventative treatments available for type 1 diabetes.
About Entelos
Entelos, Inc. (http://www.entelos.com) is a biopharmaceutical company
focused on discovering and developing new therapies for metabolic and
inflammatory disorders. Our mission is to leverage our unique predictive
capability in human biology to dramatically improve how medicines are
discovered, developed, and brought to market. Using our proprietary PhysioLab
biosimulation platforms - computer-based mathematical models of human disease,
we systematically uncover the biological mechanisms underlying a disease in
order to identify potential points of therapeutic intervention and the
patients most likely to benefit. In addition to our internal research
programs, Entelos partners with pharmaceutical and biotechnology organizations
worldwide.
Entelos and PhysioLab are registered trademarks and/or service marks of
Entelos, Inc.
All other trademarks are the property of their registered owners.
Contacts:
Entelos, Inc. McKinney Chicago
Barry Sudbeck Alan Zachary
sudbeck@entelos.com azachary@mckinneychicago.com
Tel: +1.650.572.5479 +1.708.707.6834
SOURCE Entelos, Inc.
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Related links:
http://www.entelos.com
CONTACT:
Barry Sudbeck of Entelos, Inc.,
+1-650-572-5479, sudbeck@entelos.com; or Alan Zachary of McKinney
Chicago, +1-708-707-6834, azachary@mckinneychicago.com
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