ImmVira’s global first intravenous (“IV“) administered oncolytic herpes simplex virus (“oHSV“) product MVR-T3011 IV has completed the first three cohort escalation in the U.S. Phase I clinical trial, tested dosage from 1×106 to 1×108 PFU on 10 subjects with late-stage pancreatic, colon, lung, endometrial, breast, head and neck, gastrointestinal cancers and other advanced tumors. Preliminary biodistribution and clinical results of MVR-T3011 IV demonstrated promising biological activities of MVR-T3011 IV.
I. 80% of subjects’ blood samples have pre-existing Anti-Drug antibody (“ADA“) with herpes simplex virus-1 (“HSV-1“) IgG antibody positive at baseline. Post first and repeating dose of MVR-T3011, viral DNA can be detected in blood in a dose-dependent manner with additivity from repeating dose.
II. The numbers and percentages of various types of immune cells in peripheral blood of subjects were altered post MVR-T3011 dosing, and levels of cytokines IFNγ, IL-6, IL-8, and TNFα in blood samples were altered differentially. Some patients were observed with a significant increase in IFNγ on Day 3 post-dosing representing on-target biological activities.
III. In particular, one subject in the low-dose cohort (1×106 PFU) who had continuous 17-week Stable Disease (“SD“) was observed with a significant increase in IFNγ+ CD8 cells in peripheral blood, nearly doubled after administration. In addition, RNA sequence analysis in tumor biopsy on Day 50 post first dose showed that genes related to neutrophil activation, T-cell activation, adaptive immune response, leukocyte differentiation, and cytokine secretion were notably up-regulated compared to baseline.
Intravenous injection as a delivery method remains a huge scientific and clinical challenge for oHSV candidates for many years. In application, IV dosage tends to be higher compared to intratumoral injection so that a sufficient amount of virus can reach tumor sites, countered by a higher risk of systemic cytokine storm and other severe adverse events related to a higher dosage. Moreover, generic intravenous administered viruses may be neutralized by antibodies after repeating dose. ImmVira’s proprietary breakthrough viral candidate MVR-T3011 IV is designed to become the global first clinical-stage oHSV product via intravenous injection overcoming the aforementioned challenges. ImmVira will continue to monitor and analyze ongoing clinical biodistribution data in the human body as Phase I clinical study simultaneously goes on in the U.S. and China.