Parvovirus H1 – ParvOryx
ParvOryx is an oncolytic parvovirus H1 (H-1PV), a wild type rat virus that infects and lyses tumor cells from a wide variety of cancers. These tumor types include glioblastoma multiforme, pancreatic cancer, breast cancer, lung cancer, melanoma, lymphoma, pediatric tumors such as neuroblastoma and medulloblastoma, prostate cancer and renal cancer, as well as tumor stem cells.
ParvOryx (parvus = small) is the smallest of all oncolytic viruses and is able to cross the blood brain barrier. Unlike other natural or modified oncolytic viruses currently under investigation, ParvOryx does not affect normal cells and is not pathogenic to humans.
The special properties of ParvOryx allow for both intratumoral and intravenous administration as well as repeated application (booster).
Mode of Action
H-1PV acts at relatively low multiplicities of infection. The virus exerts both cytotoxic and oncolytic (replication) effects. The cytotoxic effect is predominantly mediated by the non-structural protein (NS1), resulting in cell transcription dysregulation, cell cycle arrest, cell replication shut off, activation of cellular stress response and induction of cell death. In addition, viral oncolysis induces a strong tumor-specific immune response leading to the recognition and elimination of minimal residual disease (bystander effect).
Clinical Evidence of Efficacy
ParvOryx has successfully completed a Phase I/IIa trial to treat glioblastoma multiforme in 18 patients with recurrent or progressive disease. Topline data from a dose-escalating Phase I/IIa pilot study for the treatment of metastatic pancreatic cancer with ParvOryx monotherapy are expected in 2019. In addition, ParvOryx is currently studied in compassionate uses in combination with immune-oncology drugs such as Avastin® (bevacizumab) and various immune checkpoint inhibitors.
Data from the two Phase I/IIa trials together with data from the combination of ParvOryx with Avastin® and/or immune checkpoint inhibitors indicate that ParvOryx is able to turn an immunogenic “cold” into a “hot” tumor by profoundly changing its microenvironment. This virus-induced change to the tumor microenvironment makes the tumor vulnerable against many immuno-oncology approaches, which, based on preliminary clinical findings, appears to improve progression-free-survival (PFS) and overall survival (OS).