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TARRYTOWN, N.Y.—Regeneron Pharmaceuticals Inc. started off the week by sharing news of two clinically focused agreements in cancer, one with Plymouth Meeting, Pa.-based Inovio Pharmaceuticals Inc. and one with SillaJen Inc., a biopharmaceutical company based in Seoul, South Korea.
The deal with Inovio is a clinical study agreement for a Phase 1b/2a immuno-oncology trial, which Inovio will conduct in newly diagnosed glioblastoma multiforme (GBM) patients to assess the combination of Regeneron's REGN2810, a PD-1 inhibitor, together with Inovio's INO-5401 T cell-activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12, a cytokine that plays a role in T cell response.
"I am a strong believer in this combination regimen approach in immuno-oncology: use Inovio immunotherapies to generate killer T-cells to turn 'cold' tumors into 'hot' tumors, then block T cell suppression via checkpoint inhibition," Dr. J. Joseph Kim, president and CEO of Inovio, commented in a press release. "This step with INO-5401 is very important for us in 2017, as we believe INO-5401 has the potential to be a powerful cancer immunotherapeutic in combination with promising checkpoint inhibitors such as Regeneron's REGN2810, and we look forward to investigating its potential for GBM and multiple other challenging cancers."
Per the agreement, Inovio will solely conduct and fund the trial, based on a mutually agreed-upon study design, and Regeneron will supply its REGN2810. The two companies will jointly conduct immunological analyses of the combination therapy. This will be an open-label trial in roughly 50 patients and will be conducted at 30 U.S. sites. The trial's primary endpoints are safety and tolerability, but it will also look at immunological impact, progression-free survival and overall survival.
"The unmet need for effective therapies in GBM remains extremely high. Certain immune checkpoint inhibitors have shown efficacy in certain cancers, but evidence increasingly suggests that the benefit of checkpoint inhibitors can be enhanced when used in combination with therapies that generate T cells," said Dr. David Reardon, clinical director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School. "Inovio has an innovative immunotherapy platform which has shown the ability to generate antigen-specific T cells in disease areas including cancer. We look forward to exploring the potential of combining a T cell-generating immunotherapy encoding multiple antigens with REGN2810, a PD-1 checkpoint inhibitor."
GBM is the most aggressive type of brain cancer, and due to its rapid growth, the inherent difficulty of targeting tumors in the brain and the fact that glioblastoma often consist of several different types of cells, it is difficult to treat. There are roughly 240,000 cases of brain/nervous system tumors globally each year, and according to the American Brain Tumor Association, glioblastoma represent approximately 15.4 percent of all primary brain tumors. Patients receiving standard-of-care therapy for GBM have a median overall survival of roughly 15 months, and the average five-year survival rate for this subtype of cancer is less than 3 percent.
The agreement with SillaJen also consists of an early- phase trial featuring a combination therapy with REGN2810. SillaJen and Regeneron inked a clinical and supply agreement for a Phase 1b dose-escalation study in patients with previously treated metastatic or unresectable renal cell carcinoma (RCC), also known as kidney cancer. The companies will be evaluating REGN2810 together with Pexa-Vec, SillaJen's oncolytic vaccinia virus.
The trial will begin later in the year, opening in Korea initially and then expanding to sites in the United States. The main focus will be the safety and efficacy of this combination regimen compared to treatment with REGN2810 alone. SillaJen will fund and conduct the study based on a study design from both companies, while Regeneron will supply its drug candidate.
Pexa-Vec is SillaJen's most advanced product candidate from its Selective Oncolytic Vaccinia Engineering (SOLVE) platform. It was designed to target genetic defects in cancer cells by deleting the thymidine kinase (TK) gene, and it also expresses GM-CSF protein. As noted by SillaJen, “GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration.” Pexa-Vec seems to reverse the immunosuppressive microenvironment of a tumor by activating T cell-mediated anti-tumor immune response, which could increase sensitivity to anti-PD-1 treatment.
"Given the results reported thus far for monotherapy anti-PD1 immunotherapy and initial studies of Pexa-Vec for the treatment of advanced kidney cancer, we believe the combination of Pexa-Vec and REGN-2810 holds great promise," said Dr. James Burke, chief medical officer of SillaJen. "This combination immunotherapy approach in RCC joins the oncolytic immunotherapy expertise of SillaJen with the well-known leadership of Regeneron in antibody- targeted therapies."