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PTC299 is a novel, orally administered, small molecule designed to inhibit the production of VEGF by targeting the post-transcriptional processes that regulate VEGF synthesis. Over-expression of VEGF plays a key role in multiple diseases including cancer and macular degeneration. PTC299 is currently being developed for the treatment of cancer. It has completed Phase 1a trials in healthy volunteers, and is now being studied in a Phase 1b trial in patients with solid tumors. Additional Phase 1b/2 studies in women with metastatic breast cancer and in patients with human-immunodeficiency (HIV)-related Kaposi sarcoma and a Phase 2 clinical trial in neurofibromatosis type 2 are currently ongoing.
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 other therapies. 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.
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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