- Company Initiates Phase1b/2 Clinical Trial in Breast Cancer -
SAN ANTONIO and SOUTH PLAINFIELD, N.J., Dec. 17 /PRNewswire/ -- PTC
Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the
discovery, development, and commercialization of small-molecule drugs
targeting post-transcriptional control mechanisms announced the
presentation of preclinical and Phase 1 data regarding PTC299, its novel,
internally discovered, vascular endothelial growth factor (VEGF) inhibitor.
PTC299 is an orally bioavailable investigational drug which is designed to
inhibit the production of VEGF in tumors, acting upstream of current
anti-angiogenic agents that function at the site of the VEGF receptor. The
preclinical and clinical data presented today formed the basis for the
recent initiation of a Phase 1b/2 clinical trial of PTC299 in patients with
advanced breast cancer.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
"We are pleased to present these preclinical data on PTC299, which show
drug activity in multiple preclinical models of human cancer, including
breast cancer," said Langdon Miller, M.D., Chief Medical Officer of PTC
Therapeutics, Inc. "Based on the safety profile and pharmacokinetic results
from our Phase 1a studies, we are excited to have initiated a Phase 1b/2
trial of PTC299 in patients with advanced breast cancer. Our hope is that
PTC299 will offer an active, well-tolerated, and convenient oral therapy
for patients with breast cancer and other tumor types."
The data were detailed in a poster presentation at the San Antonio
Breast Cancer Symposium entitled, "Preclinical Efficacy in Breast Cancer
Xenografts and Phase 1 Results of PTC299, a Novel VEGF Expression
Inhibitor," (Poster Number 6082).
In the preclinical studies, PTC299 was administered to mice harboring
established human breast tumor xenografts. In these studies, PTC299
monotherapy significantly decreased human tumor and plasma VEGF levels,
impeded tumor growth, and prolonged time to tumor progression in hormone-
sensitive and -insensitive xenograft models. As assessed by dynamic
contrast- enhanced magnetic resonance imaging (DCE-MRI), PTC299 also
significantly reduced xenograft tumor volume and tumor perfusion, with
effects beginning within one day of treatment initiation.
In the Phase 1 clinical studies, healthy volunteers received single
doses or multiple doses through seven days of drug administration. PTC299
induced no serious, dose-limiting, or definitively drug-related adverse
events. All clinical adverse events were mild (Grade 1) or moderate (Grade
2) in severity and did not require intervention. Consistent with
preclinical findings which suggest that PTC299 selectively inhibits
pathological tumor-associated VEGF production while sparing physiological
VEGF expression, adverse events such as bleeding, hypertension, or
proteinuria that have been associated with other VEGF inhibitors were not
observed. Pharmacokinetic data indicated dose- proportional increases in
plasma exposures with trough plasma concentrations exceeding those
associated with activity in the preclinical models of breast cancer.
Together, these preclinical and Phase 1a clinical data have supported
the recent initiation of a randomized, dose-ranging Phase 1b/2 clinical
trial in patients with advanced breast cancer at New York University
Medical Center. In addition to assessing longer-term safety and anti-tumor
activity, the trial will evaluate tumor perfusion and metabolism and assess
circulating VEGF and tumor markers. For additional information on the
PTC299 clinical trial, please visit http://www.clinicialtrials.gov and search
using the keyword, PTC299.
"The initiation of trials with PTC299 in patients with breast cancer
provides further clinical validation of our proprietary GEMS technology.
This is an important milestone for the company," commented Stuart W. Peltz,
Ph.D., President and CEO of PTC Therapeutics, Inc. "PTC299 is an example of
the utilization of the GEMS technology to identify innovative oral small
molecules with the opportunity to change the paradigm of treatment in areas
of continued unmet medical need such as oncology and infectious diseases."
About PTC299
PTC299 is a novel, orally administered small-molecule compound that
inhibits the production of the protein vascular endothelial growth factor,
or VEGF, in tumors. PTC discovered PTC299 through PTC's proprietary GEMS
(Gene Expression Modulation by Small-Molecules) technology by targeting the
post- transcriptional processes that regulate VEGF formation.
Overexpression of VEGF plays a key role in the growth of many types of
cancers. PTC299 inhibits VEGF production through a mechanism that is
distinct from other VEGF inhibitors and has potential application in the
treatment of multiple solid tumor types.
About GEMS
Gene Expression Modulation by Small-molecules (GEMS) is PTC's novel and
proprietary screening technology for the identification of small-molecules
that modulate post-transcriptional control mechanisms. Compounds identified
through the GEMS technology target processes that act through the
untranslated regions (UTRs) of messenger RNA (mRNA) molecules. GEMS was the
basis for the discovery of PTC299 and is being used in multiple ongoing
drug discovery programs.
About Department of Defense Clinical Translational Research Award
In September 2006, the company received a $2.2 million award from the
Department of the Army to fund development of PTC299 as a potential
treatment for breast cancer. The Department of Defense Clinical
Translational Research Award sponsors innovative preclinical and
clinical/translational research that may result in substantial improvements
over current approaches to breast cancer chemoprevention and therapy. As
part of the Congressionally Directed Medical Research Programs, it
administers funds for peer-reviewed research toward specific diseases and
supports research that positively affects the health and well-being of
Americans. For this grant (grant number W81XWH-06-1- 0629), the U.S. Army
Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick,
MD 21702-5014 is the awarding and administering acquisitions office. The
content of this press release does not necessarily reflect the position or
the policy of the Government, and no official endorsement should be
inferred.
About PTC Therapeutics, Inc.
PTC is a biopharmaceutical company focused on the discovery,
development and commercialization of orally administered, proprietary,
small-molecule drugs that target post-transcriptional control processes.
Post- transcriptional control processes regulate the rate and timing of
protein production and are of central importance to proper cellular
function. PTC's internally-discovered pipeline addresses multiple
therapeutic areas, including genetic disorders, oncology and infectious
diseases. In addition, PTC has developed proprietary technologies and
extensive knowledge of post- transcriptional control processes that it
applies in its drug discovery and development activities, including the
Gene Expression Modulation by Small- molecules (GEMS) technology platform,
which has been the basis for collaborations with leading pharmaceutical and
biotechnology companies such as Pfizer, Celgene, CV Therapeutics and
Schering-Plough. For more information, visit the company's website,
http://www.ptcbio.com.
SOURCE PTC Therapeutics, Inc.
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Related links:
http://www.ptcbio.com/
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
CONTACT:
William Baird, PTC Therapeutics, Inc.,
+1-908-912-9159, wbaird@ptcbio.com, or Sheryl Seapy, Pure
Communications, +1-949-608-0841, sheryl@purecommunicationsinc.com
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