PTC Presents Encouraging Phase 1 Results Of Novel VEGF Inhibitor

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PTC Therapeutics presents 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.

"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."

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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.

"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."

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