On June 25, 2020 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported positive preclinical findings published in Frontiers in Immunology regarding the prospect of MN-166 (ibudilast) as an adjunct treatment for glioblastoma (Press release, MediciNova, JUN 25, 2020, View Source [SID1234561500]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The publication, entitled "Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression", was a collaborative effort between MediciNova and the Cleveland Clinic, led by Tyler Alban (doctoral candidate) and Dr. Justin Lathia, Co-Director of the Brain Tumor Research and Therapeutic Development Center of Excellence at the Lerner Research Institute, Cleveland Clinic, and Associate Professor, Department of Molecular Medicine at Case Western Reserve University. Dr. Lathia, Dr. Michael Vogelbaum (previously at the Cleveland Clinic, now at Moffitt Cancer Center in Tampa, FL) and colleagues previously reported on findings that GBM patients had higher levels of immune suppressive myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and they tended to be resistant to and dependent on macrophage migration inhibitory factor (MIF). In this research publication, in collaboration with Dr. Richard Bucala (Yale University), they report the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 in the tumor microenvironment. This finding is meaningful in that targeting M-MDSCs with ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, resulted in decreased MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. They note that clinical trial results to date suggest that treatment with an immune stimulatory therapy alone is not effective in treating GBM and hypothesized that better clinical outcomes will be seen when an immune stimulatory therapy is combined with ibudilast, which has been shown to reverse tumor-induced immune suppression.
Dr. Justin Lathia commented, "We found that the receptor CD74 may play a greater role in GBM MDSC biology because the subset of MDSCs primarily found in the tumor microenvironment were M-MDSCs, which predominantly express CD74 as a MIF receptor. These findings are significant for treating patients diagnosed with GBM. Among multiple anti-MIF agents we tested, ibudilast was most potent with reducing M-MDSCs. Ibudilast readily crosses the blood-brain barrier, an advantage over other agents, and has a strong safety profile. Our hope is that combining ibudilast and immune stimulatory therapy will translate to decreased disease progression in clinical trials."
Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We have an ongoing clinical trial evaluating MN-166 in combination with temozolomide for the treatment of GBM at the Dana-Farber Cancer Institute, Harvard Medical School. Recently, we expanded our target population to include patients with either recurrent or newly diagnosed GBM. A recently published GBM animal model study showed that median survival was longer in the group treated with MN-166 plus temozolomide than in the group treated with temozolomide alone. The new findings reported by Dr. Lathia and his colleagues may lead to the use of MN-166 as combination therapy with immune stimulatory treatment and may offer a new treatment option to patients with GBM, one of the most serious refractory cancers."
About Glioblastoma
According to the American Association of Neurological Surgeons, glioblastoma is an aggressive brain cancer that often results in death within 15 months of diagnosis. Glioblastoma develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. Glioblastoma is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that glioblastoma represents about 15% of all primary brain tumors and approximately 10,000 cases of glioblastoma are diagnosed each year in the U.S. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with glioblastoma. Median survival is approximately 11-15 months for adults with more aggressive glioblastoma (IDH-wildtype) who receive standard treatment of surgery, temozolomide, and radiation therapy.
About MN-166 (ibudilast)
MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. Our earlier human studies demonstrated significant reductions of serum MIF level after treatment with MN-166 (ibudilast). It also attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of amyotrophic lateral sclerosis (ALS), progressive multiple sclerosis (MS) and other neurological diseases such as glioblastoma (GBM), and substance abuse/addiction. MediciNova is developing MN-166 for ALS, progressive MS and other neurological conditions such as degenerative cervical myelopathy (DCM), glioblastoma, substance abuse/addiction, and chemotherapy-induced peripheral neuropathy. MediciNova has a portfolio of patents which covers the use of MN-166 (ibudilast) to treat various diseases including ALS, progressive MS, and drug addiction.