RedHill Reports Positive Opaganib Results for Obesity and Diabetes

The global market for obesity and diabetes drugs is anticipated to reach an estimated $100 billion by 2034. This growth is primarily fueled by Glucagon-like peptide-1 (GLP-1) inhibitors, such as Novo Nordisk's Ozempic® and Wegovy® and Eli Lilly's Trulicity® and Mounjaro®, along with sodium glucose cotransporter-2 (SGLT2) inhibitors like Boehringer Ingelheim's Jardiance®.

Recent in vivo studies have highlighted the significant impact of sphingosine kinase-2 (SPHK2) inhibition in various models of metabolic diseases. These studies support the potential application of opaganib therapy for addressing diabetes and obesity-related disorders. With its promising results, opaganib, a novel, host-directed, orally administered small molecule drug, is being developed for multiple indications, including oncology, viral infections, inflammatory diseases, and metabolic disorders.

RedHill Biopharma Ltd. (Nasdaq: RDHL), a specialty biopharmaceutical company, announced positive outcomes from several in vivo studies conducted by its partner, Apogee Biotechnology Corporation. These studies demonstrated opaganib's effectiveness in controlling weight gain and improving glucose tolerance in a high-fat diet (HFD) model. These results suggest that opaganib could be clinically useful for both preventing and treating Type 2 diabetes and other obesity-related conditions.

Charles D. Smith, Ph.D., Founder and CEO of Apogee Biotechnology Corporation, emphasized the role of sphingolipid metabolism in insulin resistance, β-cell dysfunction, adipocyte function, inflammation, immune regulation, and vascular complications. He explained that opaganib's ability to modulate multiple signaling pathways by simultaneously inhibiting three sphingolipid-metabolizing enzymes in human cells underpins its potential effectiveness in treating obesity-related disorders.

Dr. Mark Levitt, Chief Scientific Officer at RedHill, noted that sphingolipid metabolism is a crucial pathway in many diseases, including obesity, but has not been thoroughly explored as a target for human therapies. He pointed out that opaganib, a sphingosine competitor, is the first clinical drug to target three key enzymes in this pathway, paving the way for its potential use in treating metabolic diseases.

Opaganib (ABC294640) is a pioneering investigational drug, administered orally, acting as a selective inhibitor of SPHK2. Apart from its application in obesity-related syndromes, it has demonstrated anticancer, anti-inflammatory, and antiviral activities. Opaganib targets multiple diseases, including prostate cancer, cholangiocarcinoma, gastrointestinal acute radiation syndrome (GI-ARS), Sulfur Mustard exposure, COVID-19, and Ebola.

The drug's host-directed action is believed to function through the inhibition of multiple pathways, induction of autophagy and apoptosis, and disruption of viral replication. Opaganib has shown antiviral activity against SARS-CoV-2, multiple variants, and other viruses, including Influenza A and Ebola. In a U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, opaganib significantly increased survival time, marking it as the first host-directed molecule to show activity against Ebola virus disease.

Additionally, opaganib demonstrated a synergistic effect when combined with remdesivir (Veklury®, Gilead Sciences Inc.) in a U.S. Army-funded in vitro Ebola virus study, enhancing potency while maintaining cell viability. As a host-targeted therapy, opaganib is expected to remain effective against emerging viral variants. In Phase 2/3 clinical data analyses for hospitalized COVID-19 patients, opaganib showed improved viral RNA clearance, faster recovery time, and significant mortality reduction in key patient subpopulations compared to placebo.

Thus far, opaganib has shown a favorable safety and tolerability profile in over 470 individuals across various clinical studies and expanded access uses. The global Phase 2/3 study data was published in medRxiv. Opaganib has also received Orphan Drug designation from the FDA for treating cholangiocarcinoma and has been evaluated in studies for advanced cholangiocarcinoma and prostate cancer. Additionally, it has shown potential in preclinical studies for renal fibrosis and various oncological, radioprotection, viral, inflammatory, and gastrointestinal indications.

RedHill Biopharma Ltd. focuses on developing and commercializing specialty biopharmaceuticals, particularly for gastrointestinal and infectious diseases. Their product portfolio includes Talicia® for treating Helicobacter pylori infection and Aemcolo® for travelers' diarrhea. The company's late-stage development programs feature opaganib for multiple indications, including pandemic preparedness and cancer, and RHB-107 for non-hospitalized symptomatic COVID-19 and other conditions.

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