Third Candidate from Esperance's Targeted Anti-cancer Platform, EP-302, Establishes Preclinical Proof of Concept
- Data presented in a late-breaking poster session at AACR -
BATON ROUGE, La., April 20 /PRNewswire/ -- Drug discovery and
development company Esperance Pharmaceuticals today presented
positive results from their preclinical EP-302 program that support
the initiation of IND enabling studies. EP-302 is a targeted
membrane-disrupting peptide designed to selectively kill cells that
express nucleolin on their surface. Nucleolin is a protein that is
over-expressed in a wide range of cancers and tumor endothelial
cells. Results from in vitro and in vivo studies of EP-302 in 20
cancer cell lines and breast and prostate cancer xenograft models
were presented in a late-breaking poster presentation entitled,
"Nucleolin Targeting Oncolytic Peptide for Treatment of Cancers" at
the American Association for Cancer Research (AACR) 101st Annual
Meeting 2010 in Washington, DC. EP-302 is the third candidate from
the Company's Cationic Lytic Peptide (CLYP(TM)) platform
technology.
(Logo: http://www.newscom.com/cgi-bin/prnh/20090421/NE02455LOGO
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"These data not only support the continued development of
EP-302, but also validate our core CLYP(TM) platform technology,"
said Carola Leuschner, PhD, Senior Director of Biology for
Esperance and lead author of the study. "Importantly, results of
this study demonstrate that targeting nucleolin on the surface of
cancer and tumor endothelial cells is a novel mechanism for seeking
and destroying cancer cells without harming normal cells. We
believe our approach may lead to an improved safety profile for
drugs emerging from this platform compared to existing cancer
therapies such as radiation or chemotherapy."
"Based on the results observed in these most recent studies of
EP-302, Esperance is planning to initiate IND-enabling studies in
the next twelve months," said Hector Alila, PhD, President and
Chief Executive Officer of Esperance. "In addition, we continue to
make significant progress on our ongoing Phase 1 study of EP-100 in
patients with solid tumors and look forward to presenting results
from this study in 2011."
The CLYP(TM) technology platform has enabled the development of
a robust portfolio of novel targeted membrane disrupting peptides
and antibody drug conjugates to selectively bind and destroy cancer
cells that over-express target molecules on their surfaces.
Study results:
EP-302 consists of a nucleolin binding domain conjugated to a
novel membrane-disrupting peptide, CLIP 71. The drug candidate was
tested in vitro in 20 human cancer cells lines and in vivo for
activity in surface nucleolin over-expressing breast and prostate
cancer xenografts. In in vitro studies designed to test the
cytotoxicity of EP-302 in cancer cells lines across breast,
endometrial, ovarian, pancreatic, prostate, colon, lung and
hematological malignancies, cells were cultured in the presence of
various concentrations of EP-302 or unconjugated CLIP 71 for
fifteen minutes to 24 hours. As negative controls, the study
utilized surface nucleolin negative HS27 human and 3T3 murine
fibroblast cells. Results demonstrated that EP-302 was fast-acting,
destroying cancer cells that express nucleolin on their surface
within one hour. A nucleolin-binding peptide analog was not
cytotoxic.
In 16 of the 20 human cancer cell lines, EP-302 had very low
IC50 values (0.5-6.4 micromolar), suggesting high potency. EP-302
was shown to specifically bind to surface nucleolin expressing
cancer cells through western blot analysis. Co-incubation with
nucleolin binding peptide F3 resulted in competitive inhibition of
EP-302 cytotoxic activity, indicating that nucleolin binding is
necessary to achieve cytotoxicity. Additionally, no hemolytic
effects were observed in incubation with human red blood cells and
bioactivity in human plasma was retained at 60% after two hours,
suggesting high stability in human plasma.
In in vivo studies, the efficacy of EP-302 in comparison to
saline control in nude mice xenografts with breast (MDA-MB-435S)
and prostate (PC-3) cancer cell lines was evaluated. EP-302
resulted in significant (p<0.0035) tumor regression in PC-3
xenografts at doses of 0.02, 0.2 and 1 mg/kg and increased survival
of the mice. Tumor regression and increased survival was also
observed for MDA-MB-435S xenografts (p<0.0001) at all doses
tested. Histological evaluation of treated tumors showed that cell
killing was primarily by necrosis. EP-302 was well tolerated in all
treated groups. These results indicate that EP-302 selectively
targets and kills only cancer cells that have surface nucleolin
without harming healthy cells and suggest that EP-302 could be a
promising potential therapy for cancers in humans.
About Esperance Pharmaceuticals
Esperance Pharmaceuticals, Inc. is developing a new class of
targeted anticancer drugs using its Cationic Lytic Peptide
(CLYP(TM)) platform technology. These drug candidates, called
targeted membrane-disrupting peptides (tMDPs) and antibody drug
conjugates (ADCs), selectively kill cancer cells, including cells
known to be resistant to chemotherapeutic drugs, without harming
normal cells. Targeting occurs through binding to specific
receptors and antigens on the cell's surface. The Company was
founded on patented technology discovered by scientists at
Louisiana State University. Founding investors include the
Louisiana Fund I, Themelios Venture Partners and Research
Corporation Technologies. Additional investors include Louisiana
Technology Fund and private investors.
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Source: Esperance Pharmaceuticals, Inc.
CONTACT: Media Relations, Sarah Cavanaugh, MacDougall
Biomedical
Communications, +1-781-235-3060, scavanaugh@macbiocom.com
Posted: April 2010
