Seneca Valley Virus (SVV-001) is a novel native picornavirus being developed as a systemically deliverable oncolytic virus for treatment of human cancers with neuroendocrine features. In vitro, SVV-001 demonstrates selective oncolytic potency for adult and pediatric human cancer cells which express markers of neuroendocrine differentiation. In vivo, SVV-001 demonstrated efficacy in murine neuroendocrine tumor models following a single intravenous injection. In 4/4 human xenograft models and in a murine syngeneic neuroblastoma model (N1E-115), SVV-001 inhibited tumor growth and prolonged survival. In H446 (small cell lung cancer) and Y79 (retinoblastoma) xenografts, eradication of >50% of tumors was observed with doses as low as 107 and 108 vp/kg, respectively. Tumor-selective replication of SVV-001 was also observed in the syngeneic N1E-115 tumor model. Injection of SVV-001 at 109 vp/kg yielded an infectious titer of SVV-001 in tumors greater than 109 TCID50/mg at 24 hr, 6|[ndash]|8 logs higher than levels observed in normal tissues. Virus was cleared from serum by day 4 and from all normal tissues between 7 and 14 days, whereas SVV-001 persisted in tumors through day 14. In toxicological studies, SVV-001 was well tolerated in mice and pigs. No dose-limiting toxicities were observed in a 12- week study in mice at doses up to 1014 vp/kg, a million-fold higher dose than necessary to eradicate 10/10 H446 and 5/8 Y79 tumors. These data substantiate the ongoing development of SVV-001 as a systemically deliverable oncolytic virus for treatment of human cancers.