PepVax is a HLA-restricted (A*0201) single antigen [UL83 (pp65)] vaccine engineered to induce a CMV(pp65)-specific T-cell response to control the virus. Previous studies have shown that pp65 is a principal target for CD8+ cytotoxic lymphocytes, expressed both early and late following detection of CMV viremia. PepVax consists of synthetic fusion peptide, CMV-pp65495-503 A02XX CD8+ cytotoxic T Cell (CTL) epitope covalently linked to universal tetanus T-helper (TET830-843) epitope, in combination with Toll-like Receptor 9 Agonist (the “TLR-9 Agonist”), which is known to induce potent immuno-stimulatory effects in patients, including B-cell and NK cell activation, as well as pro-inflammatory cytokine production. PepVax is being developed for control of CMV reactivation in allogeneic CMV-seropositive HSCT recipients. Two previous clinical studies of PepVax have been completed, investigating the use of vaccine in both healthy volunteers and allogeneic HSCT recipients. A first Phase 1 dose-escalation study of PepVax in 65 CMV seropositive and seronegative healthy volunteers was previously conducted at a single site, City of Hope in Duarte California. Immune responses were observed in all healthy volunteers receiving the vaccine in combination with the TLR-9 Agonist. Based on the results of the Phase 1 study, PepVax was subsequently investigated in a Phase 1b pilot study in 36 CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant, randomized (1:1) between a vaccine arm and observation arm. Patients received two subcutaneous injections of PepVax four weeks apart starting on Day 28 after transplant. PepVax was observed to have excellent safety and tolerability. Patients who received the vaccine experienced a significantly lower rate of CMV reactivation, with only one of sixteen (6%) evaluable patients in the vaccine arm reactivating CMV versus six of eighteen (33%) patients who experienced CMV reactivation in the observation arm (p=0.025). The high CMV control rate observed in the Phase 1b is supported by immunological data, showing a nine-fold increase in CMV(pp65)-specific CD8+ T-cells in the vaccine arm versus the observation arm. Additionally, only one of sixteen evaluable patients in the vaccine arm experienced a relapse event (of the underlying cancer) versus seven of eighteen evaluable patients in the observation arm (p=0.0347). A number of other clinical and non-clinical benefits of PepVax were observed, including reduced duration of antiviral therapy and no increase in acute GvHD in patients receiving the vaccine. In December of 2015, the results of the Phase 1b study of PepVax were published in The Lancet Haematology. The publication can be accessed at http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(15)00246-X/abstract. Based on the promising results observed in previous studies of PepVax, and in particular the Phase 1b in recipients of allogeneic HSCT, Helocyte is now enrolling a multi-center, randomized (1:1), double-blinded, placebo-controlled Phase 2 of PepVax in 96 HSCT CMV-seropositive recipients who will receive two subcutaneous injections of PepVax (on Days 28 and 56 respectively). The primary endpoint is CMV reactivation through Day 100 post-transplantation (as monitored by PCR). However, the study will examine a number of other immunologic and clinical endpoints, including CMV cellular immunity, occurrence of acute and chronic GvHD, use of antivirals and frequency of relapse. GMP-grade clinical materials have already been manufactured in sufficient quantity to complete the Phase 2 study. The study is supported by grants from the National Cancer Institute.

For more information regarding the Phase 2 study of PepVax in Recipients of Allogeneic HSCT, please see https://clinicaltrials.gov/ct2/show/NCT01588015.  Helocyte licensed the exclusive worldwide rights to PepVax from City of Hope in April of 2015.