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PTC299 is a novel, orally administered small-molecule designed to inhibit the production of vascular endothelial growth factor (VEGF) in tumors. Overexpression of VEGF plays a key role in multiple diseases including cancer and macular degeneration. PTC299
was discovered through PTC's GEMS technology by targeting the post-transcriptional processes that regulate VEGF
formation, and is currently being developed for the treatment of cancer. PTC has completed Phase 1 studies of PTC299 in healthy volunteers and Phase 1b/2 studies in patients with breast cancer will commence in 2007.
PTC299 was designed to inhibit VEGF production in tumors. Because PTC299 inhibits VEGF production, its action occurs
at a different point in the VEGF pathway than therapies, such as Avastin® or Sutent®. PTC299 may be active both as a single agent or when used in combination
with other anti-angiogenic agents or with chemotherapy agents for the treatment of cancers. PTC299 may also prove
clinically useful in other diseases where VEGF levels play a key role, such as in age-related macular degeneration.
PTC has conducted multiple in vitro and animal preclinical studies of PTC299. Key findings of these studies include the following:
- In in vitro studies, PTC299 was a potent inhibitor of tumor VEGF production active in all
isoforms of VEGF. In these studies, PTC299 demonstrated a broad range of activity in blocking VEGF synthesis
in multiple tumor types, including breast, cervical, colorectal, fibrosarcoma, gastric, lung, melanoma,
neuroblastoma, ovarian, pancreatic, prostate and renal cell cancer lines.
- In multiple animal studies, PTC299 as a monotherapy significantly reduced VEGF concentrations in tumors and
plasma, reduced tumor blood vessel density, and substantially impeded tumor progression. In addition, in animal
studies, PTC299 enhanced the antitumor activity of chemotherapy agents and of Avastin® when given as a component
of combination therapy.
Figure 1: A comparison of various anti-angiogenesis inhibitor targets. PTC299 targets the untranslated regions of the mRNA, upstream of other VEGF inhibitors.
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