RedHill Biopharma, a specialty biopharmaceutical company, announced that opaganib has been awarded a further $1.7 million in US Government funding, via a Small Business Innovation Research (SBIR) grant to the Company's development partner, Apogee Biotechnology. This SBIR grant will support research to further the development of opaganib as a medical countermeasure (MCM) for gastrointestinal acute radiation syndrome (GI-ARS). This grant is in addition and complementary to the multimillion-dollar-valued US Government Radiation and Nuclear Countermeasures Program (RNCP) product pipeline development contract awarded to opaganib following its selection by the RNCP for ARS development.
The mission of the SBIR programs is to support scientific excellence and technological innovation through the investment of Federal research funds in critical American priorities to build a strong national economy.
Dror Ben-Asher, CEO of RedHill Biopharma, said: "In light of ongoing regional geo-political instabilities, it is important for us to bring together all the pieces of the development jigsaw for opaganib as a potential medical countermeasure for acute radiation syndrome. Opaganib is now being supported by several multimillion dollar-valued government grants. This latest additional U.S. Government funding from the SBIR, in addition to the RNCP development collaboration, is expected to help ensure that we and our partner Apogee can rapidly progress opaganib's development for ARS. In parallel, we plan to continue our existing collaborations and discussions with other U.S. Government agencies and other governments regarding opaganib for ARDS, COVID-19 and other indications, as well as for our other new chemical entity (NCE) under clinical development, RHB-107 (upamostat)."
In an ARS setting, opaganib is thought to exert its protective effects via an anti-inflammatory mechanism of action involving ceramide elevation and reduction of sphingosine 1-phosphate. This is believed to reduce inflammatory damage to normal tissue and thus suppress toxicity from unintended ionizing radiation exposure. A recent publication in the International Journal of Molecular Sciences, entitled "Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy" describes the collective results of eight U.S. Government-funded in vivo studies by Apogee, as well as additional experiments, establishing opaganib's potential radiation protection capabilities. In the relevant study models, opaganib was associated with protection of normal tissue, including the GI tract, from damage due to ionizing radiation exposure from total-body exposure. Additional independent studies demonstrate the role of inhibition of sphingosine kinase-2 (SPHK2), the primary target of opaganib, in radioprotection in bone marrow, with knockout of SPHK2 showing enhanced survival in mice irradiated with lethal doses of whole-body radiation.
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 in mass casualty nuclear radiation incidents, if approved.
About 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.
Current treatments for ARS are supportive care, including blood transfusions, antibiotics, etc., as well as the availability of four approved products to mitigate hematologic-ARS (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 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.
About Opaganib (ABC294640)
Opaganib, a new chemical entity, is an orally administered, first-in-class proprietary selective inhibitor of SPHK2 with suggested anti-inflammatory, anticancer, radioprotective and antiviral activity. The SPHK2 inhibitor 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).
In addition to development for gastrointestinal ARS, opaganib is also being developed as a host-directed antiviral against SARS-CoV-2 and other viruses and has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma. A Phase 2a study in advanced cholangiocarcinoma and a prostate cancer study is ongoing. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.
Opaganib has demonstrated broad-acting, host-directed, antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A. 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. Data from the opaganib global Phase 2/3 study has been submitted for peer review and recently published in medRxiv.
Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use.
About RedHill Biopharma
RedHill Biopharma 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, and Aemcolo®, for the treatment of travelers' diarrhea in adults[6]. 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, 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. More information about the Company is available at www.redhillbio.com/ twitter.com/RedHillBio.
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