PLYMOUTH MEETING, Pa.—Inovio Pharmaceuticals Inc. and Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc. announced in early May a clinical study agreement for a Phase 1b/2a immuno-oncology trial. The study will be conducted by Inovio in patients with newly diagnosed glioblastoma multiforme (GBM) and will evaluate Regeneron’s PD-1 inhibitor, REGN2810, in combination with Inovio’s INO-5401, a T cell-activating immunotherapy encoding multiple antigens, and INO-9012, an immune activator encoding IL-12.
“Regeneron’s approach to oncology includes evaluating the combination of innovative therapies that act on diverse pathways and targets,” commented Dr. Israel Lowy, vice president of translation sciences and oncology at Regeneron. “Using our PD-1 inhibitor as a therapeutic backbone alongside Inovio’s T cell-generating therapies offers a new path for exploration and heightens the potential to develop new, desperately needed treatment options for patients.”
The open-label trial, expected to begin later this year, is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 patients. The study will be conducted at 30 U.S. sites with the primary endpoints of safety and tolerability. The trial will also evaluate immunological impact, progression-free survival and overall survival. GBM is the most common and aggressive brain cancer and its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard-of-care therapy is approximately 15 months, and the average five-year survival rate is less than 3 percent. GBM treatment is often limited by tumor location and the ability of a patient to tolerate surgery. Consequently, it is a particularly difficult cancer to treat.
“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 a 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.”
Under the terms of the agreement, the trial will be solely conducted and funded by Inovio, based upon a mutually agreed-upon study design, and Regeneron will supply REGN2810. Inovio and Regeneron will jointly conduct immunological analyses in support of the study. Regeneron, in collaboration with Sanofi, is developing REGN2810 both alone and in combination with other therapies for the treatment of various cancers.
“I am a strong believer in this combination regimen approach in immuno-oncology: use Inovio immunotherapies to generate killer T cells, have them infiltrate into tumors—or what is being referenced as turning a tumor from ‘cold’ to ‘hot’—then block T cell suppression via checkpoint inhibition,” noted Dr. J. Joseph Kim, Inovio's president and CEO. “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.”
There’s good news for Regeneron in the financial sector as well, with its recent Dupixent launch. Canaccord Genuity healthcare analyst Dr. John Newman raised his rating on Regeneron from HOLD to BUY and said, “We believe that investor sentiment on the Dupixent launch is very strong, and is likely to drive share value higher into 2Q and 3Q17 earnings. We estimate FY17 US Dupixent revenues at $148M, and Ex-US Dupixent revenues at $67M during 2017.”
In addition to the agreement with Regeneron, Inovio has also recently announced that MedImmune, AstraZeneca’s global biologics research and development arm, will start a clinical trial investigating the combination of MEDI0457 (previously known as INO-3112), an immunotherapy designed to generate antigen specific killer T cell responses targeting HPV-associated tumors, and durvalumab (previously known as MEDI4736), an investigational PD-L1 checkpoint inhibitor.
In 2015, MedImmune acquired exclusive rights to Inovio's INO-3112 immunotherapy for all HPV-associated cancers. MedImmune provided an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs, and Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.
The combination trial will enroll patients with metastatic HPV-associated squamous cell carcinoma of the head and neck with persistent or recurrent disease after chemotherapy treatment. The open-label study is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 subjects at multiple U.S. sites. Subjects will receive multiple doses of MEDI0457 and durvalumab. The primary endpoints of the study are safety and objective response rate, and it will also evaluate immunological impact, progression-free survival and overall survival.
“MedImmune is investigating the possibility of elevating the response rate of checkpoint inhibitors by using durvalumab in combination with a DNA plasmid vaccine originally from Inovio which has shown the ability to generate killer T cells. We think that powerful combination can be effective in treating multiple tumors going forward,” Kim said.
Increasing evidence suggests that response rates from checkpoint inhibitors such as MedImmune’s durvalumab can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells. Interim data from a MEDI0457 monotherapy study of head and neck cancer patients demonstrated that MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue samples.