Pre-IND meeting planned for GBM vaccine
CAMBRIDGE, Mass.—Buoyed by new data supporting its glioblastoma multiforme (Glioblastoma or GBM) cancer immunotherapy program, VBI Vaccines Inc. is planning a pre-IND meeting with the U.S. Food and Drug Administration (FDA) in the first half of 2016.
During the November 20 poster presentation at the European Society for Medical Oncology (ESMO) Immuno-Oncology Symposium, “Therapeutic Vaccination against Glioblastoma Multiforme Using CMV gB/pp65 eVLPs Formulated with GM-CSF,” Dr. David E. Anderson, Ph.D., VBI's chief scientific officer, summarized recent milestones in VBI's development of a therapeutic glioblastoma vaccine.
Ex-vivo studies demonstrate the vaccine candidate's ability to induce desired anti-tumor immunity in peripheral blood mononuclear cells (PBMCs) harvested from healthy subjects and patients with GBM; GBM patient samples were provided by Columbia University's Brain Tumor Center. The vaccine candidate stimulated both CD4+ and CD8+ T cell responses, characterized by secretion of IFN-g and CCL3, key biomarkers associated with positive clinical outcomes. In-vivo data confirm the vaccine candidate's ability to induce desired CD4+ and CD8+ T cell responses in mice; additional animal studies are planned to determine optimal dosing and formulation properties. Characterization data confirm the desired integrity and quality of the vaccine candidate; pilot (10L) scale production is now underway at a GMP-compliant facility.
Targeted immunotherapy may provide a promising adjunct or alternative to conventional GBM treatment. Immunotherapy is a fundamentally different way of treating cancer that stimulates the patient's immune system to resume its attack on tumors. While conventional therapies are non-specific and may damage surrounding normal tissues, targeted immunotherapy may offer a highly specific and potentially long-lasting treatment approach that leverages the immune system to protect against cancer.
Developing a broadly applicable GBM immunotherapy requires the identification of antigens, used to direct the immune response, that are consistently expressed on tumor cells. A growing body of research has demonstrated that GBM tumors are susceptible to infection by cytomegalovirus (CMV), with over 90 percent of GBM tumors expressing CMV antigens. In addition, recent research has demonstrated that an anti-CMV dendritic cell vaccination regimen can extend overall survival in patients with glioblastoma. Thus, effective targeting of CMV antigens may represent an attractive strategy for a GBM immunotherapy.
VBI seeks to leverage its eVLP Platform and its expertise in anti-CMV immunity to develop a bivalent therapeutic vaccine candidate designed to direct an immune response against gB and pp65, two CMV antigens that are highly immunogenic targets during natural infection. The vaccine candidate includes granulocyte- macrophage colony-stimulating factor (GM-CSF), an adjuvant that mobilizes dendritic function and enhances Th1-type immunity.
In recently completed preclinical studies, VBI demonstrated that its vaccine candidate stimulated immune responses critical to efficacious anti-tumor immunity. In studies conducted using peripheral blood mononuclear cells (PBMCs), harvested from healthy subjects and patients with GBM, the vaccine candidate stimulated strong CD4+ and CD8+ T cell responses ex vivo, characterized by secretion of IFN-g and CCL3, key biomarkers associated with positive clinical outcomes. GBM patient samples were provided by Columbia University's Brain Tumor Center.
In a mouse study, VBI's vaccine candidate induced desired anti-tumor immunity in vivo, expanding both CD4+ and CD8+ T cell responses. Additional mouse studies are planned to determine optimal dosing and formulation properties.
"A limitation of some past therapeutic cancer vaccines, and one reason more patients do not respond to checkpoint inhibitors, is the inherently poor immunogenicity of tumor- associated antigens derived from 'self' tissues,’" said Dr. Anderson. "While early, these preclinical findings suggest that VBI's candidate, a bivalent vaccine comprised of highly immunogenic 'foreign' viral tumor-associated antigens, may be able to overcome this past issue and better activate and expand GBM-specific CD4+ and CD8+ T cell responses."
Pilot (10L) scale production of VBI's vaccine candidate is now underway at a GMP-compliant facility. During recent testing, VBI employed electron microscopy to confirm the integrity of the bivalent eVLPs, with positive interim results. Purity measurements are expected to meet regulatory requirements for clinical evaluation of the vaccine candidate.
Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal, with median patient survival of less than sixteen months.
VBI Vaccines Inc. is a biopharmaceutical company developing novel technologies that seek to expand vaccine protection in large underserved markets. VBI's eVLP vaccine platform allows for the design of enveloped ("e") virus-like particle ("VLP") vaccines that closely mimic the target virus. VBI's lead eVLP asset is a prophylactic cytomegalovirus (CMV) vaccine; VBI has initiated work for GMP manufacturing of its CMV candidate for use in formal preclinical and Phase 1 trials. VBI's second platform is a thermostable technology that enables the development of vaccines and biologics that can preserve vaccine potency and withstand storage or shipment at fluctuating temperatures. VBI has completed proof of concept thermostability studies on a number of vaccine and biologic targets. VBI is headquartered in Cambridge, MA with research facilities in Ottawa, Canada.