Fibrosis of lung caused by radiation

The data, published in the International Journal of Molecular Sciences, demonstrate that opaganib significantly improved long-term survival in an in vivo model of lung damage following exposure to ionizing radiation Opaganib is the first selective sphingosine kinase-2 (SPHK2) inhibitor investigational drug targeting sphingolipid metabolism for the treatment of radiation-induced inflammation Opaganib, a novel oral, small molecule pill with a five-year shelf-life, is easy to administer and distribute, supporting potential central government stockpiling for use as radioprotection therapy in mass casualty radiological or nuclear incidents, if approved by the FDA Opaganib is being tested as a potential treatment for Acute Radiation Syndrome (ARS) following selection by the U.S government National Institutes of Health's (NIH) Radiation and Nuclear Countermeasures Program (RNCP) for its radiation medical countermeasures Product Development Program Opaganib is being developed for multiple additional indications, including COVID-19, acute respiratory distress syndrome (ARDS), filoviruses (including Ebola) and oncology TEL AVIV, Israel and RALEIGH, N.C., Feb. 20, 2024 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced a new publication of data from multiple experiments in the International Journal of Molecular Sciences1. The published data shows that opaganib2 protects against radiation-induced lung inflammation and fibrosis in an in vivo mouse model of lung damage following exposure to ionizing radiation, demonstrating its potential use as a medical countermeasure against nuclear irradiation and in cancer radiotherapy. Radiation-induced inflammation is known to occur in two phases – in an initial inflammatory response immediately after irradiation and in a delayed response that can occur weeks later. As such, one of the experiments looked specifically at longer-term survival with two treatment windows: 1-3 days post-radiation and 31-45 days post-radiation. The opaganib group treated both during the initial and delayed phases of inflammation demonstrated a highly statistically significant improvement in survival at Day 180 (60% survival compared with 10% for controls, p=0.008). Thus, treating with opaganib during both initial and delayed phases of inflammation provided the greatest improvement in survival. "The data, when looked at collectively across multiple experiments, demonstrate that opaganib significantly improved long-term survival associated with reduced lung fibrosis, suppression of granulocyte infiltration, and reduced expression of IL-6 and TNFα in an in vivo model of lung damage following exposure to ionizing radiation," said Dr. Lynn W. Maines, lead author of the publication and VP of Research at Apogee Biotechnology Corporation, RedHill's development partner for opaganib. "These data further demonstrate that sphingolipid metabolism is a critical regulator of fibrogenesis, and specifically show that opaganib suppresses radiation-induced pulmonary inflammation and fibrosis." Opaganib is being tested as a potential treatment for Acute Radiation Syndrome (ARS), following selection by the U.S government National Institutes of Health's (NIH) Radiation and Nuclear Countermeasures Program (RNCP) for its radiation medical countermeasures Product Development Program. Opaganib was also recently selected for inclusion into the BARDA/NIH Chemical Countermeasures screening program for Sulfur Mustard exposure. Opaganib, a novel, oral, small molecule pill with a five-year shelf-life, is easy to administer and distribute, supporting potential central government stockpiling for use as a medical countermeasure in the event of mass casualty nuclear radiation incidents or Sulfur Mustard attack, if approved by the U.S. Food and Drug Administration (FDA). About Lung Inflammation, Fibrosis and Acute Radiation Syndrome (ARS) ARS, sometimes known as radiation toxicity or radiation sickness, is generally rare; however, public health emergencies, such as a nuclear power plant accident or detonation of a nuclear device, could affect large numbers of people. ARS is an acute illness caused by irradiation of the body by a high dose of penetrating radiation in a short period of time. Much of the damage caused by ARS is caused by inflammation secondary to the direct effects of ionizing radiation itself. The inflammation can occur throughout the body, but specifically, inflammation in the lungs can cause the tissue around the air sacs of the lungs (alveoli) to become damaged, thickened, and scarred – this is known as pulmonary fibrosis. As the lungs scar and stiffen, breathing becomes more difficult, and the amount of oxygen entering the blood system becomes reduced. Current treatments for ARS are supportive care, including blood transfusions, antibiotics, etc., as well as the availability of four approved products (three growth factors to address neutropenia and one to mitigate thrombocytopenia*). However, other radiation-induced clinical manifestations that have been observed in natural history studies and remain unaddressed with the current treatments include GI-ARS, cutaneous injury, and late effects in the lung, heart, and kidneys. Opaganib, an SPHK2 inhibitor, may offer a new therapeutic approach to mitigate both hematopoietic-ARS and GI-ARS. It has also been reported in the literature that inhibition of SPHK2 promotes the viability and robustness of hematopoietic stem cells, even in the face of radiation damage, supporting increased survival. * The agents are filgrastim, PEGylated filgrastim and romiplostim (Neupogen®, Neulasta® and Nplate®, all Amgen Inc., NasdaqGS: AMGN), sargramostim (Leukine®, Partner Therapeutics Inc.). About Opaganib (ABC294640) Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including gastrointestinal acute radiation syndrome (GI-ARS), COVID-19, other viruses as part of pandemic preparedness, and cholangiocarcinoma (bile duct cancer). Opaganib's host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS). Opaganib was selected by the U.S. government's Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, for the nuclear medical countermeasures product development pipeline as a potential treatment for Acute Radiation Syndrome (ARS). Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury®, Gilead Sciences Inc., Nasdaq: GILD), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study. Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv. Opaganib has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission. Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications. About RedHill Biopharma RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs Talicia®, for the treatment of Helicobacter pylori (H. pylori) infection in adults[3], and Aemcolo®, for the treatment of travelers' diarrhea in adults[4]. RedHill's key clinical late-stage development programs include: (i) opaganib (ABC294640), a first -in -class oral broad-acting, host-directed SPHK2 selective inhibitor with potential for pandemic preparedness, targeting multiple indications with a U.S. government collaboration for development for Acute Radiation Syndrome (ARS), a Phase 2/3 program for hospitalized COVID-19, and a Phase 2 program in oncology; (ii) RHB-107 ( upamostat), an oral broad-acting, host-directed, serine protease inhibitor with potential for pandemic preparedness is in late-stage development as a treatment for non-hospitalized symptomatic COVID-19, with non-dilutive external funding covering the entirety of the RHB-107 arm of the 300-patient Phase 2 adaptive platform trial, and is also targeting multiple other cancer and inflammatory gastrointestinal diseases; (iii) RHB-102, with potential UK submission for chemotherapy and radiotherapy induced nausea and vomiting, positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; and (v) RHB-204, a Phase 3-stage program for pulmonary nontuberculous mycobacteria (NTM) disease. RedHill is open to opportunities to acquire revenue generating assets in various indications, aligned to our strategic direction. Trading in RedHill's shares, ADSs and Warrants is regulated by the Securities and Exchange Commission (SEC), and the Company is committed to work in compliance with all relevant SEC and FDA regulations and requirements. More information about the Company is available at / twitter.com/RedHillBio. Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and may discuss investment opportunities, stock analysis, financial performance, investor relations, and market trends. Such statements, including, but not limited to, statements regarding the intended use of net proceeds from the offering, may be preceded by the words "intends," "may," "will," "plans," "expects," "anticipates," "projects," "predicts," "estimates," "aims," "believes," "hopes," "potential" or similar words and include statements regarding the risk that the Company will not comply with the listing requirements of the Nasdaq Capital Market ("Nasdaq") to remain listed for trading on Nasdaq, the addition of new revenue generating products, out-licensing of the Company's development pipeline assets, timing of opaganib's development for Acute Radiation Syndrome, non-dilutive development funding from RHB-107 and its inclusion in a key platform study. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company's control and cannot be predicted or quantified, and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, market and other conditions, the risk that the addition of new revenue generating products or out-licensing transactions will not occur; the risk that acceptance onto the RNCP Product Development Pipeline will not guarantee ongoing development or that any such development will not be completed or successful; the risk that the FDA does not agree with the Company's proposed development plans for opaganib for any indication, the risk that observations from preclinical studies are not indicative or predictive of results in clinical trials; the risk that the FDA pre-study requirements will not be met and/or that the Phase 3 study of RHB-107 in COVID-19 outpatients will not be approved to commence or if approved, will not be completed or, should that be the case, that we will not be successful in obtaining alternative non-dilutive development funding for RHB-107, the risk that HB-107's late-stage development for non-hospitalized COVID-19 will not benefit from the resources redirected from the terminated RHB-204 Phase 3 study, that the Phase 2/3 COVID-19 study for RHB-107 may not be successful and, even if successful, such studies and results may not be sufficient for regulatory applications, including emergency use or marketing applications, and that additional COVID-19 studies for opaganib and RHB-107 are likely to be required, as well as risks and uncertainties associated with the risk that the Company will not successfully commercialize its products; as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company's research, manufacturing, pre-clinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its commercial products and ones it may acquire or develop in the future; (ii) the Company's ability to advance its therapeutic candidates into clinical trials or to successfully complete its pre-clinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number and type of additional studies that the Company may be required to conduct and the Company's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company's therapeutic candidates and Talicia®; (v) the Company's ability to successfully commercialize and promote Talicia® and Aemcolo®; (vi) the Company's ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company's therapeutic candidates and the results obtained with its therapeutic candidates in research, pre-clinical studies or clinical trials; (ix) the implementation of the Company's business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company's expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company's industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on April 28, 2023. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise unless required by law. Company contact: Adi Frish Chief Corporate & Business Development Officer RedHill Biopharma +972-54-6543-112 [email protected] Category: Financials [1] Maines LW, Keller SN, Smith RA, Green CL, Smith CD. The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy. International Journal of Molecular Sciences. 2024; 25(4):2322. [2] Opaganib is an investigational new drug, not available for commercial distribution. [3] Talicia® (omeprazole magnesium, amoxicillin and rifabutin) is indicated for the treatment of H. pylori infection in adults. For full prescribing information see: . [4] Aemcolo® (rifamycin) is indicated for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults. For full prescribing information see: . SOURCE RedHill Biopharma Ltd.

Providence, RI, April 20, 2023 (GLOBE NEWSWIRE) -- Ocean Biomedical, Inc. (NASDAQ: OCEA), a biopharma company working to accelerate the development and commercialization of scientifically compelling assets from research universities and medical centers, announced today that its Scientific Co-founder Dr. Jack A. Elias, received a Notice of Allowance from the United States Patent and Trademark Office (“USPTO”) for his U.S. patent application covering a therapeutic molecule that Ocean Biomedical is working to advance into the clinic for patients suffering from pulmonary fibrosis. Discoveries in recent years by Ocean Biomedical’s Scientific Co-founder, Dr. Jack A. Elias, and his colleagues at Brown University, have revealed a new target and a new pathway for treating pulmonary tissue damage in Idiopathic Pulmonary Fibrosis (IPF). This patent allowance covers pulmonary fibrosis caused by multiple conditions including: idiopathic pulmonary fibrosis (IPF), genetic pulmonary fibrosis such as Hermansky-Pudlak Syndrome (HPS), chemotherapy and radiation-induced pulmonary fibrosis, and exposure-induced interstitial lung diseases including asbestosis and silicosis. A Notice of Allowance is issued after the USPTO examines a patent application and determines that the applicant should be granted a patent from the application. Ocean Biomedical anticipates that a patent will be issued by the USPTO from Dr. Elias’ application in the coming months. Ocean Biomedical’s novel approach to treating pulmonary fibrosis – a condition with no disease modifying agents currently available – is focused on inhibiting Chitinase 1 (Chit1) with patented “OCF-203.” Chit1 is also a critical biomarker in Scleroderma-associated interstitial lung disease (SSc-ILD) and plays a role in bleomycin- and IL-13-induced pulmonary fibrosis. In four pulmonary fibrosis animal models, Ocean Biomedical’s OCF-203 has shown an 85% – 90% reduction in collagen accumulation. The results of this antifibrotic (termed molecule X: SMX) in the bleomycin model can be seen in the diagram below. Results also showed efficacy in the pale-ear mouse model of HPS, including impressive reductions in fibrosis. As a result, efforts are now moving towards IND-enabling studies. Ocean Biomedical’s anti-fibrosis platform seeks to address major unmet needs for IPF and HPS, and has shown potential for expanded application into fibrotic diseases in other organs, such as scleroderma, alcoholic liver disease, NASH, and kidney failure (see below). This unique approach has been developed by a research team led by Dr. Jack A. Elias, who is the former Dean of Medicine and Biology at Brown University, and former Chair of Medicine and Chief of Pulmonology and Critical Care Medicine at Yale University and Yale-New Haven Hospital. IPF is a devastating lung condition that currently affects about 100,000 people per year in the United States, and about 15 per 100,000 people worldwide, with a much higher prevalence in males over 50 years old. The median survival rate ranges from 2 – 5 years. Current standard-of-care therapeutics have limited efficacy and significant side effects such that patients choose to forgo drug therapy. There are no therapies currently available that can reverse loss of lung function. “It is difficult to see the limited treatment options that are currently available for patients with pulmonary fibrosis conditions. We are working to change that, and we’re excited about the broad therapeutic potential for this unique treatment pathway,” commented Dr. Elias. “We are confident in the results being generated in our anti-fibrosis platform, and we are proud to be moving them forward, especially with the potential application for these pulmonary fibrotic conditions that do not currently have effective treatment options,” said Elizabeth Ng, CEO of Ocean Biomedical. Suren Ajjarapu, a director of Ocean, commented, “The range of pulmonary fibrosis conditions that can be impacted by this patent allowance is impressive and has potential to generate positive returns for our shareholders in multiple ways.” “This company was founded by physician-researchers to find solutions for large, unmet medical needs and we are pleased with the possibility of extending the anti-fibrosis platform into a broad range of hard-to-treat conditions,” said Dr. Chirinjeev Kathuria, Ocean’s co-founder and Executive Chairman. About Ocean Biomedical Ocean Biomedical, Inc. (“Ocean Biomedical” or the “Company”) is a Providence, Rhode Island-based biopharma company with an innovative business model that accelerates the development and commercialization of scientifically compelling assets from research universities and medical centers. Ocean Biomedical deploys the funding and expertise to move new therapeutic candidates efficiently from the laboratory to the clinic, to the world. Ocean Biomedical is currently developing five promising discoveries that have the potential to achieve life-changing outcomes in lung cancer, brain cancer, pulmonary fibrosis, and the prevention and treatment of malaria. The Ocean Biomedical team is working on solving some of the world’s toughest problems, for the people who need it most. To learn more, visit . Forward-Looking Statements The information included herein and in any oral statements made in connection herewith include “forward-looking statements” within the meaning of the “safe harbor” provisions of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “estimate,” “plan,” “project,” “forecast,” “intend,” “will,” “expect,” “anticipate,” “believe,” “seek,” “target,” or other similar expressions that predict or indicate future events or trends or that are not statements of historical matters, although not all forward-looking statements contain such identifying words. These forward-looking statements include but are not limited to: the expected timing and success of investigational new drug (“IND”) filings for our initial product candidates; statements regarding the expected timing of our IND-enabling studies; the frequency and timing of filing additional INDs; expectations regarding the availability and addition of future assets to our pipeline; the advantages of any of our pipeline assets and platforms; the potential benefits of our product candidates; potential commercial opportunities; the timing of key milestones for our programs; the future financial condition, results of operations, business strategy and plans, and objectives of management for future strategy and operations; and statements about industry trends and other companies in the industry. These forward-looking statements are based on various assumptions, whether or not identified herein, and on the current expectations of the Company’s management, and they are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by any investor as, a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Any discoveries announced by the Company are based solely on laboratory and animal studies. Ocean Biomedical has not conducted any studies that show similar efficacy or safety in humans. There can be no assurances that any treatment tested by the Company will prove safe or effective in humans, and any clinical benefit of any such treatment is subject to clinical trials and ultimate approval of its use in patients by the FDA. Such approval, if granted, could be years away. Forward-looking statements are predictions, projections, and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. These forward-looking statements are not guarantees of future performance, conditions, or results, and involve a number of known and unknown risks, uncertainties, assumptions, and other important factors, many of which are outside the control of the Company that could cause actual results or outcomes to differ materially from those discussed in the forward-looking statements. Important factors, among others, that may affect actual results or outcomes include but are not limited to: recently transitioning to operating as a NASDAQ-listed public company with a limited operating history; our ability to successfully complete our pre-clinical trials and for those trials to produce positive results; our ability to timely obtain approval of INDs from the FDA in the future; the timing of the initiation, progress and potential results of our planned pre-clinical studies and clinical trials and our research programs; our ability to access additional product candidates from research universities and medical centers; the timing or likelihood of regulatory filings and approvals; the commercializing of our product candidates, if approved; our product development and marketing strategy; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials and for commercial use, if approved; future strategic arrangements and/or collaborations and partnerships, and the potential benefits of such arrangements; our assessment that the early observations from our pre-clinical studies are encouraging; the potential for IND-enabling studies and future clinical trial results to differ from initial results or from our pre-clinical studies; regulatory developments in the United States and other countries; difficulties in managing our growth; our estimates regarding expenses, future revenue, capital requirements and needs for financing and our ability to obtain capital; the sufficiency of our existing and anticipated capital to fund our planned operating expenses; our ability to retain the continued service of our key personnel and to identify, hire and retain additional qualified professionals; the implementation of our business model and strategic plans for our business and product candidates; the scope of protection we are able to establish and maintain for intellectual property rights, product candidates and our pipeline; our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately; the pricing, coverage and reimbursement of our product candidates, if approved; developments relating to our competitors and our industry, including competing product candidates and therapies; changes in the markets in which the Company competes, including with respect to its competitive landscape, technology evolution, or regulatory changes; changes in domestic and global general economic and market conditions; risks related to the ongoing COVID-19 pandemic and response, including supply chain disruptions; the risk that the Company may fail to keep pace with rapid technological developments to provide new and innovative products and services or make substantial investments in unsuccessful new products and services; the outcome of any legal proceedings that may be instituted against the Company; the risk of product liability or regulatory lawsuits or proceedings relating to the Company’s business; the risk of cyber security or foreign exchange losses; the risk that the Company is unable to secure or protect its intellectual property; the risk that the Company may not be able to develop and maintain effective internal controls; the ability to develop, license, or acquire new therapeutics; the risk that the Company will need to raise additional capital to execute its business plan, which may not be available on acceptable terms or at all; and those factors discussed in the Company’s filings with the SEC. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties that are described in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, and which are described in the “Risk Factors” section of the Company’s definitive proxy statement filed by the Company on January 12, 2023, and other documents to be filed by the Company from time to time with the SEC and which are and will be available at . These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements. These forward-looking statements should not be relied upon as representing the Company’s assessments as of any date subsequent to the date of this filing. Accordingly, undue reliance should not be placed upon the forward-looking statements. Ocean Biomedical Investor Relations OCEANIR@westwicke.com Ocean Biomedical Media Relations OCEANPR@westwicke.com Kevin Kertscher Communications Director