MIF

VIENNA--(BUSINESS WIRE)-- OncoOne, a biotechnology company focused on discovering precision medicines for cancer and autoimmune diseases, announced today the formation of a clinical advisory board to provide strategic and clinical insights for the company’s lead program in immunology, ON104. ON104 is a monoclonal antibody targeting the oxidized isoform of the macrophage migration inhibitory factor (oxMIF) for the treatment of chronic inflammatory diseases. “The growing amount of preclinical data for ON104 is very promising and illustrates its broad applicability in key indications such as RA, inflammatory bowel disease, asthma, and nephritis,” commented Randolf Kerschbaumer, Ph.D., CEO of OncoOne. “As we continue to validate our technology’s ability to effectively neutralize disease progression in autoimmune diseases, this board of distinguished experts will be invaluable to the clinical strategy for ON104 and will support OncoOne’s vision of supplying a new class of therapeutic solutions to patient populations with a high unmet medical need.” The members of the OncoOne Clinical Advisory Board include: Richard Bucala, M.D., Ph.D. Richard Bucala, is the Chief of Rheumatology, Allergy & Immunology at the Yale Institute for Global Health and the Waldemar Von Zedtwitz Endowed Professor of Medicine, Pathology, Epidemiology, & Public Health at the Yale School of Medicine. Dr. Bucala is renowned in MIF research and is recognized for discovering MIF's receptor CD74, as well as elucidating MIF's critical role in regulating glucocorticoid immunosuppression. He is an attending physician in the Yale New Haven Health System and is the past Editor-in-Chief of Arthritis & Rheumatology. Dr. Bucala was elected to the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP), in addition to having served on an advisory board for the United Nations and various other U.S. federal, academic, and pharmaceutical organizations. Daniel Aletaha, M.D. Daniel Aletaha is Professor and Head of the Clinical Department of Rheumatology at the Medical University of Vienna. Dr. Aletaha is the current president of the European Alliance of Associations for Rheumatology (EULAR). His research focuses on arthritis and other inflammatory rheumatic diseases, precision medicine, and the management of complex diseases. He has experience in the areas of novel therapies and treatment strategies, diagnosis, prognosis, outcomes, and biomarkers. He currently holds over 350 indexed publications. Seamas Donnelly, M.D. Dr. Seamas Donnelly is a Professor of Medicine at Trinity College Dublin. He is a global leader in translational medicine with a research focus on the development of novel compounds as anti-inflammatory/anti-cancer therapies. He has authored many MIF-focused publications in renowned peer-reviewed journals, including Nature Medicine and Molecular Medicine. Dr. Donnelly’s research epitomizes classical bench to bedside on an international scale, and, in recognition of this, has been awarded an Honorary Professorship in Translational Medicine by the University of Edinburgh. He is the current President of the Association of Physicians of Great Britain & Ireland, the leading academic medical association in the UK and Ireland. Dr. Donnelly is also the lead Trinity PI of Health Innovation Hub Ireland and has been a member of OncoOne’s scientific advisory board since 2022. Michael Freissmuth, M.D. Dr. Freissmuth is the Director of the Center of Physiology & Pharmacology as well as the Chairman of the Institute of Pharmacology at the Medical University in Vienna. He was appointed Professor of Pharmacology in 1995 and received many awards, including the Novartis Award for Medicine. Dr. Freissmuth is a member of numerous editorial boards and serves on several review panels and scientific advisory boards. His most recent appointments include positions on international panels such as the Scientific Advisory Board of the Institut Cochin de Génétique Moléculaire in Paris and of the Engelhorn Foundation for Life Sciences. He is also a member of the supervisory board of Boehringer Ingelheim Austria. Dr. Freissmuth is an inaugural member of OncoOne’s scientific advisory board, where he continues to support the development of the company’s pipeline of biotherapeutics. About OncoOne OncoOne seeks to overcome the limitations of targeting macrophage migration inhibitory factor by harnessing the disease-related isoform, oxidized macrophage migration inhibitory factor (oxMIF). The Company is focused on developing multiple proprietary drug modalities to leverage oxMIF’s potential as a target for systemic treatment of cancer, as well as for chronic inflammatory diseases. Equipped with a successful track-record in early-stage drug development, as well as a deep understanding of the target itself, OncoOne’s leadership will advance a pipeline based on oxMIF’s promise in inflammation and other disease areas. View source version on businesswire.com: Contacts For OncoOne: Randolf Kerschbaumer, Ph.D., CEO Website: E-mail: contact@oncoone.com Phone: +43 1 909 2208 - 6000 For Media Inquiries: Trophic Communications Desmond James E-mail: OncoOne@trophic.eu Phone: +49 1516 7859086 Source: OncoOne View this news release online at:

LA JOLLA, Calif., March 12, 2024 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that MediciNova’s collaborator, Perenlei Enkhbaatar, MD, PhD, FAHA, Professor, Department of Anesthesiology, Director, Translational Intensive Care Unit, Charles Robert Allen Professor in Anesthesiology, University of Texas Medical Branch, presented new data and results of a nonclinical study evaluating MN-166 (ibudilast) in a chlorine gas-induced acute lung injury (CIALI) model at the Society of Toxicology (SOT) 63rd Annual Meeting and ToxExpo in Salt Lake City, Utah. The primary objective of this nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) following ALI induced by chlorine (Cl2) gas inhalation in a clinically relevant translational ovine model. In this study, single-dose and multi-dose treatments were evaluated. The primary endpoint was the mean change in the pulmonary function measure PaO2/FiO2, which is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. Additional endpoints included survival, lung mechanics, lung injury, and edema formation evaluated by chest x-ray. The highlights of the presentation, entitled “Evaluation of safety and pharmacological activity of MN-166 (ibudilast) in a clinically relevant ovine model of chlorine-induced acute lung injury” (Abstract # 4296), are as follows: After a Cl2 gas challenge (210 ppm x 30 min) to induce moderate ALI (mean PaO2/FiO2<200 mmHg), the test subjects were randomly assigned to 4 treatment groups: MN-166 (ibudilast) low dose (10 mg) or high dose (20 mg), a positive control (rolipram 1 mg), and vehicle (negative control). Cl2 gas concentration of 210 ppm x 30 min was expected to result in a 20 - 30% mortality rate (Fukuda 2015). Treatment regimens: Single-dose treatment (n=5/group) in which a 30-min IV infusion was given once only, initiated 30 min after completion of the Cl2 challenge Multi-dose treatment (n=3/group) in which 30-min IV infusions were given a total of 4 times, initiated 30 min after the completion of Cl2 gas challenge, then every 12 hours Efficacy Result Single-dose treatment MN-166 (ibudilast) 20 mg and rolipram treatment resulted in greater improvement in mean PaO2/FiO2 and peak airway pressure but dissipated after Hour 12 Multi-dose treatment MN-166 (ibudilast) 20 mg showed greater improvement in mean PaO2/FiO2 ratio (p=0.0001), with animals recovering enough to no longer meet the criteria of ARDS (Berlin ARDS definition 2012) MN-166 (ibudilast) 20 mg also showed greater improvement in peak airway pressure (p<0.05), plateau airway pressure (p<0.05), pulmonary artery pressure (p<0.05), and lung injury score (p<0.05) compared to the other treatment groups MN-166 (ibudilast) 20 mg also maintained cardiac and kidney function compared to the other treatment groups Notably, significance was observed beyond the T=12-hour timepoint, further reinforcing the observed benefit of MN-166 (ibudilast) 20 mg with the multi-dose treatment regimen Survival MN-166 (ibudilast) 20 mg treatment demonstrated a greater survival benefit than the other treatment groups. All animals in the MN-166 (ibudilast) 20 mg group (8 out of 8) survived the 48-hour monitoring period, while 25% (2 out of 8 / arm) animals were euthanized early in other groups upon reaching the euthanasia criteria. Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "We are very pleased to report the positive results in which MN-166 demonstrated a large and significant improvement in pulmonary function and recovery, i.e., no longer having ARDS, attenuation of lung injury, and a higher survival rate in the ovine CIALI model study. Collectively, positive findings from this clinically relevant ovine model, the previously reported lipopolysaccharide (LPS)-induced ARDS nonclinical model, and significant positive results from a clinical trial in hospitalized COVID-19 patients at risk of developing ARDS, we believe MN-166 (ibudilast) shows promise as a candidate for ALI.” This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50121C00022. 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 such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS). About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline 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 pro 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 (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in Long COVID and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through 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. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” 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 such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, 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 expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when 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, 2023 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 intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: Geoff O'Brien Vice President MediciNova, Inc. info@medicinova.com

Living in neighborhoods with more white residents and greater lifetime experiences of racial discrimination are linked to increased systemic inflammation during pregnancy among Black women, according to new research. Living in neighborhoods with more white residents and greater lifetime experiences of racial discrimination are linked to increased systemic inflammation during pregnancy among Black women, according to new research led by a team from Penn State. The study, published in the February issue of the journal Brain, Behavior, & Immunity -- Health, found that these social-environmental factors were associated with higher levels of a protein that has been connected to chronic stress and an elevated risk of preterm birth. The findings shed light on the distinctive stressors that Black women face and how they may influence pregnancy outcomes, the researchers said. "Understanding these unique stressors might give us a better shot at trying to intervene," said Christopher Engeland, professor of biobehavioral health at Penn State and senior author of the paper. "We know that the preterm birth rate is almost two times higher in Black women compared to white women, but it's not fully explained by established risk factors such as socioeconomic status. We wanted to look at stressors that are both unique to the experience of Black women and potentially related to preterm birth to see if those associations might yield information about this ongoing health problem and could account for some of the disparities in pregnancy outcomes." Babies born before full-term, or 37 weeks of pregnancy, are at greater risk for death, health complications and disabilities, according to the Centers for Disease Control and Prevention. However, preterm birth rates haven't budged over the last 10 years, hovering between 9.6% and 10.5%. In 2022, 10.4% of babies were born early. Among Black women, the preterm birth rate was 14.6%. Doctors and researchers don't fully understand all the factors that contribute to preterm birth or the underlying mechanisms, the researchers said. However, inflammation may be an important piece of the puzzle. Generally, in late pregnancy, both pro-inflammatory cytokines and inflammation increase. This appears to be related to increased prostaglandin synthesis, which is important for inducing contractions, and the onset of labor, Engeland explained. Cytokines are small proteins that help manage inflammation in the body and can be a marker for inflammation. When systemic inflammation and pro-inflammatory cytokines are elevated more than normal, this is associated with a higher risk for preterm birth. When disparities exist within a specific subgroup of individuals, the researchers said it can be informative to look within that subgroup to understand their unique experience and how that may drive the underlying differences in health outcomes. Among Black women, systemic inflammation tends to be higher overall, whether they are pregnant or not, the researchers said. Studies have begun to look at psychosocial and social-environmental factors linked to chronic stress to see if those factors might lead to higher inflammation in the body and, subsequently, risk for preterm birth. For the current study, the research team was interested in investigating two factors -- experiences of racial discrimination and perceived neighborhood racial composition -- and determining if these factors predicted cytokine levels during pregnancy. The prospective study involved a cohort of 545 Black women who were between the ages of 18 and 45 years old and pregnant with only one fetus. They were recruited during their first prenatal visit to clinics in Columbus, Ohio, and Detroit, Michigan, metropolitan areas. Data were collected at three time points during their pregnancy: 8- to 18-weeks, 19- to 29-weeks and 30- to 36-weeks gestation. Participants were asked to complete surveys about their lifetime experiences of discrimination, perceived racial segregation, depressive symptoms and demographic characteristics. The researchers also took blood samples to monitor pro-inflammatory and anti-inflammatory cytokines. The study found that reports of higher lifetime racial discrimination, higher levels of depressive symptoms early in pregnancy and living in neighborhoods with more white individuals were each associated with higher levels of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF). They didn't observe a relationship with any other cytokine. "This particular cytokine has a distinctive relationship with stress. Aside from inflammation, it may be a biomarker of chronic stress and it may have something to do with the mechanism underlying preterm birth," Engeland said. Higher MIF levels are associated with glucocorticoid resistance, which means that our bodies are more prone to mount a more robust inflammatory response, he explained. Previous studies have linked MIF to chronic stress and preterm birth, which suggests a potential role in adverse pregnancy outcomes. The researchers said the study is one of the first to examine if and how neighborhood racial composition contributes to systemic inflammation during pregnancy in Black women. The relationship between MIF and neighborhood racial composition was present at all three timepoints and strongest in late pregnancy. MIF levels also appeared to increase in a stepwise fashion as neighborhood composition changed from mostly Black to some Black to mixed to mostly white neighborhoods. "It suggests that there's something about living in neighborhoods with a higher proportion of white individuals that's eliciting stress for these African American women who are pregnant. This cytokine seems to be particularly sensitive to it," said Molly Wright, a graduate student at Penn State and lead author of the study. "The fact that we saw this association across all timepoints suggests that this wasn't a spurious finding." The findings point to the need to consider neighborhood context, racial discrimination and other distinctive chronic stressors that Black individuals frequently experience when considering factors that might influence preterm birth risk, according to the researchers. They plan to follow up this study by comparing gestational age at birth and MIF levels within the same cohort of women to determine any relationship to preterm birth. Other authors on the paper are Carmen Giurgescu, professor and associate dean for research and principal investigator of the broader study, University of Central Florida College of Nursing; Dawn P. Misra, chair of the department of epidemiology and biostatistics, Michigan State University College of Human Medicine; and Jaime C. Slaughter-Acey, currently an associate professor of epidemiology at the University of North Carolina Gillings School of Global Public Health. At the time the research was conducted, Slaughter-Acey was affiliated with the University of Minnesota School of Public Health. The National Institute on Minority Health and Health Disparities funded this work.