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RedHill's Opaganib Protects Against Radiation-Induced Lung Inflammation and Fibrosis - New Publication

https://finance.yahoo.com/news/redhills-opaganib-protects-against-radiation-120000115.html
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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 TNFa 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.