Combination of Novel Gene Therapy and Immunotherapy Being Evaluated for Synergistic Anti-Tumor Activity in Patients with Cancer with Limited Treatment Options

OKAYAMA, Japan I September 11, 2019 I Momotaro-Gene, a clinical-stage biotherapeutics company developing novel gene therapies for the treatment of cancer, today announced the dosing of the first patient in a Phase 2 clinical trial combining MTG201, the company’s lead therapeutic candidate, with the PD-1 inhibitor nivolumab (Opdivo®) in patients with relapsed malignant pleural mesothelioma.  The combination of MTG201 and a PD-1 inhibitor has demonstrated a robust synergistic anti-tumor effect in a preclinical model of malignant mesothelioma.

MTG201 is a novel investigational gene therapy with unique dual  mechanisms of action capable of addressing a range of cancers.  The drug candidate leverages the company’s proprietary adenoviral vector technology platform to deliver the Reduced Expression in Immortalized Cells/Dickkopf-3 gene (REIC/Dkk-3 gene) into cancer cells, where the expression of the gene has been shown to be markedly downregulated.  The resulting increase in REIC/Dkk-3 gene expression in cancer cells triggers immunogenic cell death selectively in cancer cells. At the same time, increased expression of REIC/Dkk-3 gene in normal cell components in tumor tissue promotes anti-tumor immunity by activating dendritic cells and natural killer (NK) cells while suppressing immune suppressive regulatory T cells (Tregs)  and myeloid derived suppressor cells (MDSC). Based on these novel dual mechanisms, MTG201 is believed to be well positioned to work synergistically with checkpoint inhibitors such as nivolumab. 

The Phase 2 trial (NCT04013334), which is being conducted at the Baylor College of Medicine in Houston, Texas, is an open-label, single-arm study designed to assess the efficacy, safety and tolerability of intratumoral administration of MTG201 in combination with nivolumab.  The trial will enroll up to twelve patients with malignant mesothelioma who have failed front-line systemic platin-based chemotherapy.  The primary objective of the study is to assess efficacy of the treatment combination with the primary endpoint being objective response rate (ORR).  Secondary efficacy endpoints will include disease stabilization, duration of response, progression-free survival and overall survival.  Investigators will also evaluate traditional safety measures, exploratory biomarkers of activity and the immunogenicity of MTG201.

“The initiation of this Phase 2 clinical trial represents a key milestone in the ongoing development program for MTG201 as it will allow us to build upon the promising results achieved in our two Phase 1 trials of the treatment.  Importantly, this study will provide us the very first human data highlighting the therapeutic potential of combining MTG201 with a checkpoint inhibitor, a combination which we believe has significant promise based on preclinical studies,” said Hitoshi Shiomi, chief executive officer of Momotaro-Gene Inc.  “We look forward to working with our collaborators at the Baylor College of Medicine on this important study and continuing to advance MTG201 as a potential treatment for patients suffering with a range of cancers.”

“Mesothelioma represents an aggressive cancer for which new treatment options are desperately needed.  This is especially true for relapsed forms of the disease, for which there are currently no approved therapies,” said Bryan Burt, M.D., associate professor of surgery at Baylor College of Medicine and the principal investigator for the study. “Based on preclinical research that my team has conducted on the combination of MTG201 and an anti-PD-1 checkpoint inhibitor, we believe that the synergistic combination of these two therapies may hold promise in this patient population.  We are pleased to have the opportunity to conduct this exciting study at the Baylor College of Medicine and look forward to the results of the trial.”

Momotaro-Gene has completed two Phase 1 trials of MTG201, demonstrating encouraging safety and tolerability  in patients with malignant mesothelioma and localized prostate cancer.  In a Phase 1 study conducted with relapsed malignant pleural mesothelioma patients in Japan by Kyorin Pharmaceuticals, a partner of Momotaro-Gene, MTG201 demonstrated promising efficacy by inducing durable disease stabilization.

About Mesothelioma

Mesothelioma is a cancer that occurs in the mesothelium, the thin layer of tissue that covers the lungs and other organs. Mesothelioma is associated with exposure to asbestos in most cases. According to the World Health Organization, there are a total of 59,000 cases of mesothelioma worldwide each year. Most mesotheliomas begin as one or more nodules that progressively grow to form a solid coating of tumor surrounding the lung leading to eventual suffocation and death. There is currently only one approved treatment for mesothelioma and there are no approved therapies for relapsed forms of the cancer. Relapsed mesothelioma is highly aggressive with a median time to disease progression of only six weeks.

About Momotaro-Gene Inc.

Momotaro-Gene is a private, clinical-stage biotherapeutics company developing novel gene therapies for the treatment of cancer.  The company has developed Ad-REIC, a proprietary adenoviral vector technology capable of  delivery of the Reduced Expression in Immortalized Cells/Dickkopf-3 gene (REIC/Dkk-3 gene).  Expression of the REIC/Dkk-3 gene is markedly downregulated in a broad range of human cancer cells. Momotaro-Gene has demonstrated that forced expression of REIC/Dkk-3 gene in tumor tissue  induces immunogenic cell death of cancer cells and augmentation of  anti-tumor immunity. In addition to the Phase 2 study with malignant pleural mesothelioma in combination with nivolumab, MTG201 is currently being investigated in patients with malignant pleural mesothelioma, hepatocellular carcinoma and glioblastoma multiforme in Japan.

SOURCE: Momotaro-Gene