VCN-01 is a tumor-selective replication-competent adenovirus expressing PH20 hyaluronidase. PH20 is a glycosylphosphatidylinositol (GPI)-anchored enzyme that degrades hyaluronan (HA), an important structural element of tumor extracellular matrix. Several studies demonstrate that hyaluronan blocks the action of various chemotherapeutic agents since it creates a dense environment around tumor that increases interstitial pressure and inhibits drug entry and diffusion into the tumor mass. Moreover, the concentration of hyaluronan is elevated in pancreatic cancers, and correlates with its invasive and metastatic behavior. Expression of hyaluronidase from VCN-01 facilitates penetration and decreases intratumoral fluid pressure, enhancing intratumoral virus spread. In addition, VCN-01 capsid has been modified to allow the virus to partially evade liver tropism and target selectively the tumor after intravenous administration.
Extensive preclinical studies with VCN-01 in animal models demonstrate a good toxicology profile of the virus, both in mice and hamsters. Moreover, VCN-01 improves the therapeutic outcome compared to a similar virus without hyaluronidase when tested by intravenous or intratumoral administration in different tumor models.
There are currently on-going two independent Phase I dose escalation clinical trials with VCN-01 alone or in combination with nab-paclitaxel/gemcitabine to determine its tolerability and obtain first evidences of antitumoral activity. In one of them VCN-01 is injected intratumorally there times (https://clinicaltrials.gov/ct2/show/NCT02045589) . In the second study a single dose of VCN-01 is injected intravenously in patients with advanced solid tumours (https://clinicaltrials.gov/ct2/show/NCT02045602).