Lung Injury

Researchers may have discovered a mechanical explanation for instability observed in the lungs in cases of acute respiratory distress syndrome (ARDS), particularly in the aftermath of respiratory illnesses such as COVID-19 or pneumonia. Researchers at the University of Minnesota Twin Cities may have discovered a mechanical explanation for instability observed in the lungs in cases of acute respiratory distress syndrome (ARDS), particularly in the aftermath of respiratory illnesses such as COVID-19 or pneumonia. The research was recently published in the Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences. Currently, there is no known cure for ARDS, a life-threatening lung injury that allows fluid to leak into the lungs. The researchers in this study say that as many as two thirds of all patients that passed away from COVID-19 had ARDS. There is not a clear reason on why specific people with a severe respiratory illness may develop ARDS, while others may not, but researchers in this study were looking to find that answer. They identified the concentration of a lysolipid -- a byproduct of the immune response to viruses and bacteria -- that can have a major impact in adults suffering from ARDS. Increased concentration of this chemical eliminates the surfactant, a complex composed of fats and proteins generated in the lungs. The result is uneven lung inflation and, ultimately, respiratory distress in adults. "This study looked into the correlation of the concentration of the lysolipid in the lungs. Once that fluid reached a certain level, it started to cause severe impacts," said University of Minnesota Department of Chemical Engineering and Materials Science Professor Joseph Zasadzinski and lead professor on the research. "Your average everyday person usually won't need to think about this, but if a virus or infection is bothering your lung surfactant system and you end up in the hospital, then it could become top of mind very quickly," Zasadzinski added There are a natural amount of these lysolipids that exist in the human body, and as long as those stay below a specific concentration, the average person can breathe normally. When someone has a bad infection, those lysolipids increase, which can lead to respiratory distress. Once a patient is headed in that direction, there are not many ways of reversing those symptoms. "This research shows frequency dependence, or how quickly you open and close the lungs. This could help doctors try to tailor the treatment process for each specific patient," said Clara Ciutara, a 2023 Ph.D. chemical engineering and materials science graduate and first author of the study. Previous research of neonatal respiratory distress syndrome (NRDS) in premature infants found that it could be treated by introducing replacement lung surfactant, but that was not the case in adults. It is the amount of lysolipid that determines the outcome of the surfactant in the lungs, not the breakdown of the existing lung surfactant. The next step in the research will be to translate these ideas into a clinical environment and test to see if they can manipulate specific molecules to make them less active or stick to a specific place. This could help drop the concentration of the lysolipids to a threshold that may be able to reverse symptoms of ARDS and put people on the road to recovery. In addition to Zasadzinski and Ciutara, the research team included University of Minnesota Department of Chemical Engineering and Materials Science NIH postdoctoral fellow Steven V. Iasella, undergraduate student Boxun Huang, and former postdoctoral associate Sourav Barman. This work is supported by a grant from National Institutes of Health (NIH) Heart, Lung, and Blood Institute. All microscopy images were obtained at the University Imaging Center at the University of Minnesota.

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

─Accelerated Phase 2 CM-101 PSC Trial Timeline with Topline 15-Week Data Now Planned for Midyear 2024 and Topline Open Label Data Expected in Late 2024/Early 2025─ ─Cash Runway Extended through End of First Quarter 2025 as a Result of Early Completion of Phase 2 PSC Trial and Effective Financial Management─ ─2023 Achievements Position Chemomab for a Potentially Transformational 2024─ TEL AVIV, Israel, March 7, 2024 /PRNewswire/ -- Chemomab Therapeutics, Ltd. (Nasdaq: CMMB), a clinical stage biotechnology company focused on the discovery and development of innovative therapeutics for fibro-inflammatory diseases with high unmet need, today announced financial and operating results for the full year and fourth quarter ended December 31, 2023, and provided a corporate update. "In 2023 Chemomab achieved great progress, positioning the company for what we believe could be major catalysts in 2024 and early 2025," said Adi Mor, PhD, co-founder, Chief Executive Officer and Chief Scientific Officer of Chemomab. "The superb work of our clinical and medical teams enabled us to complete patient enrollment in our Phase 2 primary sclerosing cholangitis (PSC) trial ahead of schedule and move up the topline readout to midyear 2024. Building on the positive data we have reported from our Phase 2a clinical trial in patients with liver fibrosis, we expect a successful readout would be a potential major catalyst for Chemomab, providing the first substantial clinical proof-of-concept for CM-101 and affording us the potential to advance to a registrational trial in consultation with the FDA, with an End-of-Phase 2 meeting possible later this year. We also look forward to a second readout from the trial's open label extension, expected in late 2024 or early 2025, which we believe will provide additional clinical data on longer-term safety and activity, as well as another potential catalyst. Additionally, I am proud that our team has accomplished so much while maintaining tight fiscal discipline. As a result, we have been able to extend our cash runway until the end of the first quarter of 2025." Dr. Mor continued, "We started the year reporting positive safety and activity data from our Phase 2a trial in liver fibrosis patients, showing that CM-101 demonstrated consistent positive effects across a range of biomarkers associated with fibrosis and inflammation. Our multiple scientific presentations and publications during the year further confirmed the role of our CCL24 target in driving key fibro-inflammatory pathways and CM-101's ability to interrupt these disease processes." Dr. Mor added, "We are collaborating with thought leaders and advocates who are working to build consensus around the use of non-invasive biomarker and imaging endpoints that will facilitate the conduct of late-stage PSC clinical trials. We are encouraged by the emerging view that these regulatory changes are both feasible and essential to advance new treatments for this rare orphan disorder that currently lacks any FDA-approved therapies." Dr. Mor concluded, "The success of our Phase 2 PSC trial would be transformational for Chemomab, potentially allowing us to advance into a Phase 3 trial and to initiate additional clinical trials in other indications. We invite you to attend our upcoming webinar on Breaking New Ground: Expert Perspectives on Primary Sclerosing Cholangitis scheduled for April 10, 2024, and look forward to reporting on our further progress during the year." 2023 and Recent Highlights: In January, 2024, Chemomab reported publication of new proteomics research in the peer-reviewed journal Cells reinforcing the clinical potential of CM-101 in primary sclerosing cholangitis. In January, 2024, Chemomab announced early completion of patient enrollment in the CM-101 Phase 2 PSC SPRING trial and moved up the expected topline data readout to midyear 2024. In November, 2023, Chemomab presented new data at ACR Convergence 2023 further confirming that its CCL24 target is a major driver of the fibrotic and inflammatory processes underlying systemic sclerosis (SSc) and other fibro-inflammatory diseases. In November, 2023, Chemomab announced that CM-101 had received FDA Fast Track designation for the treatment of PSC in adult patients. In November, 2023, at AASLD's The Liver Meeting® 2023, Chemomab hosted several presentations. An oral presentation of new proteomic patient data highlighted the unique association of the company's CCL24 target with key PSC pathways and provided further evidence that CM-101 ameliorates these damaging effects. In June, 2023, Chemomab announced a new publication in the peer-reviewed journal JCI Insight demonstrating the key role of CCL24 in PSC and presenting data showing how CM-101 interrupts the fibro-inflammatory processes underlying the disease. In June, 2023, at the 2023 EASL Congress, Chemomab hosted a late-breaking presentation reporting new positive data from its CM-101 Phase 2a liver fibrosis trial. In June, 2023, Chemomab announced that Adi Mor, PhD, had been reappointed to the role of Chief Executive Officer. Sigal Fattal was reappointed as Chief Financial Officer. Nissim Darvish, MD, PhD, was appointed Chairman of the Board. The company also announced that it was implementing cost-reduction measures that extended its cash runway to the end of 2024. In June, 2023, Chemomab presented patient data at the 2023 EULAR Congress showing that serum CCL24 levels can predict the vascular and fibrotic complications of systemic sclerosis. In May, 2023, Chemomab presented data at the 2023 EASL Biliary Conference reinforcing the pro-inflammatory role of CCL24 in PSC and other cholestatic diseases. In February, 2023, Chemomab received FDA IND clearance for a CM-101 Phase 2 trial in SSc patients. Chemomab has not yet initiated patient enrollment in this trial. In January, 2023, Chemomab reported topline results from its Phase 2a Liver Fibrosis trial in NASH patients demonstrating that CM-101 met its primary endpoint of safety and tolerability and showed positive activity across multiple liver fibrosis biomarkers and physiologic assessments. Full Year and Fourth Quarter 2023 Financial Highlights: Cash Position: Cash, cash equivalents and short-term bank deposits were $19.9 million as of December 31, 2023 compared to $39.9 million as of December 31, 2022. Research and Development (R&D) Expenses: R&D expenses were $3.1 million for the fourth quarter and $18.4 million for the full year ended December 31, 2023, compared to $5.9 million and $17.0 million for the respective periods in 2022. The decrease in R&D expenses in the fourth quarter of 2023 compared to the fourth quarter of 2022 figure primarily resulted from the early completion of patient enrollment in the company's CM-101 Phase 2 PSC trial. General and Administrative (G&A) Expenses: G&A expenses were $0.8 million for the fourth quarter and $7.1 million for the full year ended December 31, 2023, compared to $2.7 million and $11.6 million for the fourth quarter and full year in 2022. The decrease in G&A expenses reflected selected reductions in headcount, and reductions in share-based payments and recruitment costs. Net Loss: Net loss was $3.4 million, or a net loss of $0.01 per basic and diluted Ordinary Share, for the fourth quarter and $24.2 million, or a net loss of $0.10 per basic and diluted Ordinary Share for the year ended December 31, 2023, compared to a net loss of $8.3 million, or a net loss of $0.04 per basic and diluted share, for the fourth quarter of 2022 and $27.6 million, or a net loss of $0.12 per basic and diluted Ordinary Share, for the full year ended December 31, 2022. The weighted average number of Ordinary Shares outstanding, basic and diluted was 234,998,859 (equal to 11,749,943 ADSs) for the year ended December 31, 2023, and 227,589,288 (equal to 11,379,464 ADSs) for the year ended December 31, 2022, respectively. For further details on the company's financial results for the year ended December 31, 2023, please refer to the company's annual report on Form 20-F, which will be filed with the SEC later this month. About Chemomab Therapeutics Ltd. Chemomab is a clinical stage biotechnology company developing innovative therapeutics for fibro-inflammatory diseases with high unmet need. Based on the unique and pivotal role of CCL24 in promoting fibrosis and inflammation, Chemomab developed CM-101, a monoclonal antibody that neutralizes CCL24 activity. In clinical and preclinical studies, CM-101 appears safe, with the potential to treat multiple severe and life-threatening fibro-inflammatory diseases. Chemomab has reported positive results from three clinical trials of CM-101 in patients, including a Phase 2a liver fibrosis trial in NASH patients and an investigator-initiated study in patients with severe lung injury. A Phase 2 trial in primary sclerosing cholangitis has completed patient enrollment, with topline data expected midyear 2024. Chemomab's CM-101 program for the treatment of systemic sclerosis is Phase 2-ready. For more information about Chemomab, visit chemomab.com. Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements include, among other things, statements regarding the clinical development pathway for CM-101; the expectation that Chemomab will report topline data from the PSC clinical trial by mid-year 2024; the length, duration and impact of the war in Israel on Chemomab's business and operations; the future operations of Chemomab and its ability to successfully initiate and complete clinical trials and achieve regulatory milestones; the nature, strategy and focus of Chemomab; the development and commercial potential and potential benefits of any product candidates of Chemomab; and that the product candidates have the potential to address high unmet needs of patients with serious fibrosis-related diseases and conditions. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon Chemomab's current expectations. Forward-looking statements involve risks and uncertainties. Because such statements deal with future events and are based on Chemomab's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Chemomab could differ materially from those described in or implied by the statements in this presentation, including those found under the caption "Risk Factors" and elsewhere in Chemomab's filings and reports with the SEC. Chemomab expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Chemomab's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law. Contacts: Media and Investors: Barbara Lindheim Consulting Vice President, Investor & Public Relations, Strategic Communications Phone: +1 917-355-9234 [email protected] [email protected] SOURCE Chemomab Therapeutics Ltd