On November 11, 2021 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 that Grazia Ambrosini, PhD, an associate research scientist at Columbia University Vagelos College of Physicians and Surgeons, presented data regarding MN-166 (ibudilast) in a uveal melanoma (UM) model study at the 10th Annual CURE OM Global Science Meeting held online as a part of the Society for Melanoma Research International Congress on October 28, 2021 (Press release, MediciNova, NOV 11, 2021, View Source [SID1234595283]).

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This study was a collaborative effort between MediciNova and Dr. Ambrosini, Richard D. Carvajal, MD, associate professor of medicine at Columbia Vagelos College of Physicians and Surgeons and co-director of the Precision Oncology and Systems Biology research program at the Herbert Irving Comprehensive Cancer Center (HICCC), and Gary Schwartz, MD, professor of oncology at Vagelos College of Physicians and Surgeons, Division Chief of Hematology/Oncology at Columbia University Irving Medical Center, and Deputy Director at the HICCC.

The highlights of Dr. Ambrosini’s presentation are follows:

The role of UM exosomes in the crosstalk with hepatic cells was investigated in co-culture migration assays and in a mouse metastatic model.
UM exosomes induce activation of cell signaling pathways and the release of cytokines and growth factors from hepatocytes. The exosome-stimulated hepatocyte conditioned media (HCM) could in turn induce migration of UM cells.
Macrophage migration inhibitory factor (MIF) was the major player in these mechanisms and its blockade inhibited cell migration in co-cultures with exosome-stimulated hepatocytes and prevented the development of metastases in vivo.
MN-166 reduced migrated UM cell count in UM-exosome-stimulated HCM (p<0.001).
Quantified bioluminescence intensity for each animal in the abdominal region was significantly reduced by MN-166 treatment in the UM mouse model (p<0.05).
MN-166 prevented metastasis in a mouse UM metastasis model.
Dr. Carvajal commented, "We are excited about the preclinical data generated with the MIF inhibitor MN-166 in this uveal melanoma model study. Uveal melanoma is the most common primary intraocular malignancy and nearly half of patients ultimately will develop metastasis. Metastases are most frequently localized to the liver and associated with a poor prognosis. Currently there are no effective preventive treatments for uveal melanoma. Previously, our group identified MIF as a critical mediator of metastatic spread. In our new study, MN-166 treatment prevented remote metastasis in the orthotopic uveal melanoma model."

Kazuko Matsuda, M.D. Ph.D, MPH., Chief Medical Officer, MediciNova, Inc., commented, "In clinical practice, cancer metastasis is often the major driver of cancer-related death rather than the primary cancer. We are very excited about MN-166’s potential to prevent metastasis in uveal melanoma. We previously reported that MN-166 reduced levels of immune suppressive myeloid-derived suppressor cells (MDSCs) and enhanced CD8 T cell activity in the tumor microenvironment. The new data from this UM model study suggested that treatment with MN-166 can potentially address significant unmet medical needs for novel and effective therapies for patients with UM at risk of metastasis. We are looking forward to moving to a clinical trial and we are optimistic that this project could help patients with uveal melanoma and other malignancies."

About MN-166 (ibudilast)

MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases including ALS, progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) is being evaluated in patients at risk for developing acute respiratory distress syndrome (ARDS).