Formation of new blood vessels (angiogenesis) is important for tumor growth in
neurofibromatosis type 2 (NF2). It is known that tumors make a protein called vascular
endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood
of many patients with NF2. VEGF stimulates the formation of blood vessels that supply the
tumor with nutrients and oxygen. PTC299 is an oral drug that has been shown to decrease
production of VEGF in animal models of human cancer. In these animal models, oral PTC299
administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood
vessel numbers in the tumor, and significantly slows or halts tumor growth. Safety studies in
research animals indicate good tolerability at doses and drug levels that are higher than
those planned for the clinical studies. Results from Phase 1a studies in healthy volunteers
indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active
in animal models of human tumor. This Phase 2 study is designed to test the hypothesis that
PTC299 will be tolerable and will show evidence of VEGF reduction, antitumor activity, and
hearing improvement when administered orally to patients with NF2.