RedHill Biopharma Ltd. announced that the U.S. Patent and Trademark Office (USPTO) had issued a Notice of Allowance for a new opaganib[1] patent covering sphingosine kinase 2 inhibition treatment for Ebola virus disease, supporting opaganib pro tection until October 2035. The Company also announced that the European Patent Office has granted RHB-102 (BEKINDA)[2] a new patent, covering ondansetron extended-release solid dosage forms for treating either nausea, vomiting or diarrhea symptoms. This new patent is expected to provide protection of RHB-102 across multiple indications until March 2035. About RHB-102 (BEKINDA): RHB-102 is a proprietary, bimodal release, once-daily oral pill formulation of the antiemetic drug ondansetron, targeting several gastrointestinal indications.

RHB-102 24 mg is intended to provide patients with relief from nausea, vomiting and diarrhea symptoms for a full 24-hour period with a single oral tablet. If approved for marketing by the MHRA, RHB-102 24 mg could become the first oral 24hr extended-release 5-HT3 antiemetic drug in the UK indicated for the treatment of CINV/RINV.  Positive results from two successful late-stage RHB-102 studies at different doses, the U.S. Phase III GUARD gastroenteritis study (RHB-102 24 mg) and the U.S. Phase II IBS-D study (RHB-102 12 mg) were published in JAMA Network Open and The American Journal of Gastroenterology, respectively. 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 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 recently 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). As part of this collaboration, contractors directed and supported by the RNCP will undertake studies, designed in collaboration with RedHill, to test opaganib in established ARS models.

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 (S1P) in human cells - suppressing inflammatory damage to normal tissue and thus suppressing toxicity from unintended ionizing radiation exposure. It has also been reported in the literature that inhibition of sphingosine kinase 2 promotes the viability and robustness of hematopoietic stem cells, even in the face of radiation damage, supporting increased survival. 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 demonstrated 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.