RedHill Biopharma Ltd (RDHL)

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RedHill Biopharma's Positive Opaganib Weight Loss & Diabetes Data Published: Signals Potential $100B Market Disruption

https://finance.yahoo.com/news/redhill-biopharmas-positive-opaganib-weight-110000215.html

GLP-1 comparable efficacy: Opaganib's positive results, newly published in the journal Diabetes, Metabolic Syndrome and Obesity, demonstrated weight loss and improved metabolic markers on par with semaglutide in preclinical models
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Novel mechanism of action, formulation and administration: Opaganib is a differentiated oral, non-peptide therapeutic that targets sphingosine kinase-2 (SPHK2), potentially avoiding common Glucagon-like peptide-1 (GLP-1) inhibitor side effects and administration burdens
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Market disruptor potential: The rapidly growing global obesity-diabetes drugs market is projected to be worth around $100 billion by 2034[1] – largely driven by GLP-1 inhibitors like Novo Nordisk's Ozempic® and Wegovy® and Eli Lilly's Trulicity®, Zepbound® and Mounjaro®
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Potential high value and de-risked development pathway: Existing human safety and tolerability data from over 470 subjects, from several clinical programs, may help expedite the FDA pathway to approval; new obesity and diabetes indications add strategic expansion and value to existing development programs in oncology, inflammatory and viral indications

TEL AVIV, Israel and RALEIGH, N.C., April 16, 2025 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced the new publication[2] of positive in vivo data, in the journal Diabetes, Metabolic Syndrome and Obesity, in an article entitled "Opaganib Promotes Weight Loss and Suppresses High-Fat Diet (HFD)-Induced Obesity and Glucose Intolerance". The data indicates that opaganib[3] effectively suppresses the loss of metabolic control in mice on a HFD, suggesting that opaganib, alone and in combination with semaglutide, is associated with improved glucose tolerance, decreased deposition of fat, weight loss and the prevention of weight gain rebound after removal of semaglutide.

Dr. Mark Levitt, Chief Scientific Officer at RedHill, said: "Sphingolipid metabolism is implicated in insulin resistance, ß-cell disruption, adipocyte function, inflammation and immune regulation, vascular complications and energy metabolism – all significant components of obesity, diabetes and their associated complications. The studies showed that treatment with opaganib markedly suppressed weight gain in mice fed the HFD but not in mice given the control diet (CD). Compared with mice given CD, mice on the HFD demonstrated poor glucose tolerance at 8, 12 and 16 weeks, consistent with the progression of obesity. Importantly, opaganib treatment of the HFD-fed mice abolished this developing glucose intolerance at all times of measurement. Opaganib treatment also reduced the elevation of hemoglobin A1c and the deposition of inguinal fat in HFD-fed mice. Opaganib and semaglutide were equally effective in promoting body weight loss and improving glucose tolerance in obese mice. Opaganib's ability to modulate multiple signaling pathways through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells – the first known clinical drug to do so - provides a strong rationale for evaluation of opaganib in obesity-related disorders – and, as a first-in-class, orally administered, non-peptide option, opaganib could potentially represent a game-changing opportunity in the multi-billion-dollar obesity and diabetes market."

The global obesity-diabetes drugs market is projected to be worth around $100 billion by 2034 – largely driven by GLP-1 inhibitors like Novo Nordisk's Ozempic and Wegovy (semaglutide) and Eli Lilly's Trulicity (dulaglutide) and Mounjaro / Zepbound (tirzepatide).

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 indications, including several cancers, diabetes and obesity-related disorders, gastrointestinal acute radiation syndrome (GI-ARS), chemical exposure indications, COVID-19, Ebola and other viruses as part of pandemic preparedness.

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).

Several U.S. government countermeasures and pandemic preparedness programs have selected opaganib for evaluation for multiple indications, including Acute Radiation Syndrome (ARS), Ebola virus disease and others. Funding bodies include the Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. government Department of Health & Human Services' National Institutes of Health and the Administration for Strategic Preparedness and Response's (ASPR) Center for Biomedical Advanced Research and Development Authority (BARDA).

A Bayer-supported 80-patient placebo-controlled randomized Phase 2 study has also been initiated to evaluate the efficacy of opaganib in combination with Bayer's darolutamide in men with metastatic castrate-resistant prostate cancer (mCRPC), testing the potentially enhancing effect of opaganib in patients with a poor prognosis.

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury®, Gilead Sciences Inc.), 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 Microorganisms.

Opaganib has received several orphan-drug designations from the FDA in oncology and other diseases and has undergone studies in solid tumors (Phase 1), 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, gastrointestinal and diabetes/obesity-related indications.