LA JOLLA, Calif., April 20, 2022 (GLOBE NEWSWIRE) — MediciNova, Inc., a biopharmaceutical company listed on the NASDAQ Global Market (NASDAQ: MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (code number: 4875) , today announced that data demonstrating that MN-166 (ibudilast) prevents metastasis in an animal model of uveal melanoma (UM) has been published in the journal Molecular cancer research.
The publication titled “Uveal Melanoma Exosomes Induce a Prometastatic Microenvironment through Macrophage Migration Inhibitory Factor” was co-authored by MediciNova collaborators Dr. Grazia Ambrosini, Research Scientist at Herbert Irving Comprehensive Cancer Center (HICCC), Columbia University Medical Center; Alex J. Rai, PhD, associate professor of pathology and cell biology, Columbia University Irving Medical Center; 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 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 of HICCC.
The publication describes a preclinical study that characterized the proteomic content of uveal melanoma exosomes and identified the presence of markers with metastatic properties. The study included an evaluation of MN-166 (ibudilast) in a model of metastatic uveal melanoma.
Key takeaways from the post include:
- Uveal melanoma exosomes (UM-exo) induce activation of cell signaling pathways and release of cytokines and growth factors from hepatocytes. These exosome-stimulated liver cells could in turn induce the migration of UM cells.
- Pro-inflammatory macrophage cytokine migration inhibitory factor (MIF) was overexpressed in UM exosomes and was a major player in these mechanisms. MIF blockade inhibited the migration of UM cells in co-cultures with exosome-stimulated hepatocytes and prevented the development of metastases in vivo.
- Most cytokine inhibitors and hepatocyte-derived growth factors had little or partial effect in blocking the migration of UM cells to exosome-stimulated hepatocytes.
- The MIF inhibitor MN-166 (ibudilast) significantly inhibited UM cell migration (p
- In the metastatic UM mouse model study,
- The quantified intensity of the bioluminescence signal in the abdominal region was significantly reduced by MN-166 (ibudilast) treatment (p
- Histological analysis of hepatic tissues from control mice showed the presence of clusters of tumor cells, which were not present in the hepatic tissues of mice treated with MN-166 (ibudilast).
- MN-166 (ibudilast) prevented metastasis in the metastatic UM mouse model.
- This study provided the first in vivo evidence that MIF inhibition can serve as a novel adjuvant drug therapy to prevent metastasis in uveal melanoma.
- MIF inhibition with MN-166 (ibudilast) may prevent metastatic spread in patients with uveal melanoma and help address the critical unmet need for new and effective adjuvant therapies.
Kazuko Matsuda, MD, PhD, MPH, Medical Director of MediciNova, Inc. commented, “We are very pleased that details of the research data regarding MN-166 preventing metastasis in the metastatic UM mouse model study have been published. Cancer metastases are often the main cause of cancer-related death rather than the primary cancer. We previously reported that MN-166 reduced levels of immunosuppressive myeloid suppressor cells (MDSCs) and increased CD8 T cell activity in the tumor microenvironment. Data from this metastatic UM model study suggest that treatment with MN-166 has the potential to address significant unmet medical needs for novel and effective therapies for patients with UM at risk of metastasis. We are optimistic that MN-166 could help patients with MU 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 advanced clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis) and DCM (cervical degenerative myelopathy); and for glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy) and substance use disorders. In addition, MN-166 (ibudilast) is being evaluated in patients at risk of developing acute respiratory distress syndrome (ARDS).
MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad portfolio of novel small molecule therapies for inflammatory, fibrotic and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3 ready for progressive multiple sclerosis ( SEP). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in glioblastoma, patients at risk of developing acute respiratory distress syndrome (ARDS), and substance dependence. MN-001 (tipelukast) has been evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and is in preparation for a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD). MediciNova has a strong track record of obtaining investigator-sponsored clinical trials funded by government grants.
Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements regarding the future development and effectiveness of MN-166, MN-001, MN-221 and MN-029. These forward-looking statements may be preceded, followed or otherwise include the words “believes”, “expects”, “anticipates”, “intends”, “estimates”, “projects”, “may”, “could”. ‘, ‘may’, ‘will’, ‘would’, ‘consider’, ‘plan’ or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to, the risks of obtaining a future partner or grant for the development of MN-166, MN-001, MN -221, and MN-029 and the risks of raising sufficient capital if needed to fund MediciNova’s operations and its contribution to clinical development, the risks and uncertainties inherent in clinical trials, including the potential cost, expected schedule, and risks associated with clinical trials designed to meet FDA requirements the direction and viability of further development considering these factors, the risks of developing and commercializing the product , uncertainty as to whether clinical trial results will be predictive of results at later stages of product development, risk of delay ds or failure to obtain or maintain regulatory approval, risks associated with the use of third parties to sponsor and fund clinical trials, risks regarding information, intellectual property rights in product candidates and the ability to defend and to enforce these intellectual property rights, the risk of default by third parties on which MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as intended, the risk of increased costs and delays due delays in the initiation, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of anticipated filings with regulatory authorities, MediciNova’s collaborations with third parties, the availability of funds to complete product development plans and the MediciNova’s ability to obtain third-party funding for the programs and to raise sufficient capital if needed, and the other risks and uncertainties described in MediciNova’s filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 202 1 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intention or obligation to revise or update these forward-looking statements.