MALVERN, Pa.--(Business Wire)--
Promedior, Inc., a leader in the development of novel therapeutics for the
treatment of fibrotic diseases and tissue remodeling, announced today the
publication of results from preclinical studies demonstrating that human Serum
Amyloid P (hSAP) potently inhibited fibrosis in two independent model systems of
kidney fibrosis. The study results indicate a potential role for hSAP in
treating kidney diseases such as diabetic nephropathy and transplant nephropathy
where interstitial fibrosis plays a significant pathological role. The results
are published in the November 4, 2009 issue of Science Translational Medicine,
and confirm previously published data demonstrating the broad anti-fibrotic
activity of SAP in models of pulmonary fibrosis and cardiac fibrosis.
Acute and chronic tissue injuries stimulate a primary innate injury response
that is broadly similar across all tissues, including the kidney. These injuries
are first recognized by the innate immune system through novel exposure and
release by injured tissues of damage-associated molecular patterns, also known
as danger molecules. Recognition of these danger molecules by the innate immune
system activates monocyte-derived cell populations to orchestrate the injury
response. Whether the outcome of this innate injury response is resolution of
injury and restoration of normal tissue homeostasis or progressive fibrotic
disease is controlled by the type of cell populations that are recruited to, and
activated at, the site of injury.
In this collaborative research study led by Dr. Jeremy Duffield of the Brigham
and Women`s Hospital and Harvard Medical School, hSAP mediated its suppressive
function by recognition of danger molecules on damaged cells and tissues at
sites of injury. This recognition by hSAP was specific, Ca++-dependent and
caused hSAP and the attached danger molecules to bind to, and be cleared by, the
Fcγ family of receptors (FcγRs) on macrophages. The result of this activity was
that hSAP suppressed inflammatory and fibrotic gene and protein expression in
monocyte-derived cells recruited to the injured tissue and potently blocked
fibrosis, an effect that depended upon expression of the anti-inflammatory
cytokine IL-10.
"These study results are encouraging and demonstrate that hSAP has the potential
to block very aggressive fibrotic pathology caused by a variety of injuries,"
said Mark Lupher Jr., Ph.D., Senior Vice President, Discovery Research at
Promedior. "This represents a novel approach to treating renal fibrosis as well
as other monocyte-driven diseases. hSAP is unique in its ability to suppress
multiple monocyte-derived cell populations playing a pathogenic role in
fibrosis, and to do so specifically at the site of injury."
In the studies, hSAP was administered systemically to mice that received either
unilateral ureteric obstruction or unilateral ischemia reperfusion mediated
kidney injury. In both settings, hSAP potently suppressed fibrotic collagen
protein and collagen gene expression and these effects were sustained throughout
the duration of each study.
"We were very impressed with the robustness of the hSAP data, particularly at
later time points in the study," said Jeremy Duffield, M.D., Ph.D., Assistant
Professor of Medicine, Brigham and Women`s Hospital and Harvard Medical School.
"We typically don`t see such sustained responses with other anti-fibrotic
approaches."
Promedior`s lead product candidate, PRM-151 (rhSAP), is a recombinant form of
human Serum Amyloid P, a highly conserved natural human serum protein that
mediates its anti-fibrotic activity by targeting the specific monocyte and
macrophage cell populations that orchestrate fibrosis and tissue remodeling.
PRM-151 has demonstrated an outstanding safety profile and robust preclinical
efficacy by reducing fibrosis in multiple tissues, organs, and disease models.
Promedior initiated a Phase 1 clinical trial of PRM-151 in July 2009 to evaluate
the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of
ascending single intravenous doses of PRM-151.
About Promedior, Inc.
Promedior is a product-focused biopharmaceutical company developing novel
therapeutics for the treatment of fibrotic diseases and tissue remodeling.
Fibrosis is a key component of multiple diseases affecting all tissues and organ
systems and is a leading cause of morbidity and mortality for millions of people
worldwide. Promedior has developed a novel platform to treat fibrotic diseases
which focuses on targeting the specific monocyte and macrophage cell populations
that orchestrate fibrosis and tissue remodeling. This new paradigm for treating
fibrotic diseases is upstream and dominant to traditional approaches and takes
advantage of universal biology common to all tissues to promote healing without
scarring.
Current investors include Morgenthaler Ventures, Polaris Venture Partners,
HealthCare Ventures and Easton Capital. For more information about Promedior,
please visit www.promedior.com.
Promedior, Inc.
Dominick Colangelo
Chief Executive Officer
610-560-1435
Copyright Business Wire 2009
