PTC Therapeutics, Inc. Presents Encouraging Phase 1 Results of its Novel VEGF Inhibitor, PTC299, at 30th Annual San Antonio Breast Cancer Symposium

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.

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"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 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, www.ptcbio.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

Web site: http://www.ptcbio.com//