On July 1, 2025 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported the initiation of patient recruitment into the Phase 2 study evaluating the efficacy of opaganib3 in combination with darolutamide4 in men with metastatic castrate-resistant prostate cancer (mCRPC), sponsored by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Ltd (Press release, RedHill Biopharma, JUL 1, 2025, View Source [SID1234654196]). (ANZUP) in Australia, and supported by Bayer (ETR: BAYN) and Ramsay Hospital Research Foundation. The Company also announced the study will recruit people across at least 10 sites across Australia and New Zealand.
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Led by Professor Lisa Horvath, from Sydney’s Chris O’Brien Lifehouse, and ANZUP, the innovative 60-participant placebo-controlled randomized study is designed to test the potentially enhancing effect of opaganib in overcoming resistance to standard of care androgen receptor pathway inhibition (ARPI) treatment.
The unique study will utilize a companion lipid biomarker test (PCPro5) to select mCRPC patients who have poor prognosis to standard of care treatment, and who may benefit from an opaganib + darolutamide combination approach to treatment. The study’s primary endpoint is improved 12-month radiographic progression-free survival (rPFS). Several secondary and exploratory endpoints will also be evaluated.
Cancer cells can block apoptosis (programmed cell death), an important cell-level process designed to help the body get rid of unneeded or abnormal/unhealthy cells, which are critical in fighting the spread of cancer. Prior research shows that opaganib enhances androgen receptor signaling inhibitor efficacy in vitro6, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS), and may potentially provide the key to overcoming darolutamide resistance in men with mCRPC.
Prostate cancer is the second most diagnosed cancer in the world with around 1.5 million new cases per year, causing almost 400,000 deaths every year, while millions more people are living with prostate cancer resulting in a significant burden of disease.7 The global prostate cancer market was worth approximately $12 billion in 2023.8
About the Study
The study is a double-blind, placebo-controlled randomized Phase 2 trial, adding opaganib to darolutamide in people with mCRPC and poor prognosis (as defined by plasma lipid signature, PCPro). The target population of the study is people with mCRPC who have had no treatment with newer, potent AR signaling inhibitors including darolutamide, enzalutamide, apalutamide, or abiraterone. 200 people with prostate cancer who are identified as potentially eligible will have a 5-ml plasma sample taken for PCPro testing. Those who are PCPro-positive (estimated 40% of patients) and agree to enter the study will be randomized on a 1:1 ratio to either the darolutamide 600mg bid + placebo (n=30) arm or the darolutamide 600 mg bid + opaganib 500 mg bid (n=30) arm. The study is registered on clinicaltrials.gov (NCT04207255).
About Prostate Cancer
Prostate cancer is the second most diagnosed cancer in the world with around 1.5 million new cases annually – causing around 400,000 deaths, with millions more people living with prostate cancer, resulting in a significant burden of disease. Globally, the number of cases of prostate cancer increased by almost 120% from 1990 to 20199.
When prostate cancer spreads outside of the prostate to other parts of the body (such as the lymph nodes or bones) it is classified as advanced or metastatic prostate cancer10. Five-year survival rates for prostate cancer diagnosed at Stage 1 is 100%; this drops to just 28% for people with Stage 4 (advanced) disease.
About Androgen Receptor Pathway Inhibitors (ARPI)
ARPI is a key therapeutic strategy in treating prostate cancer, particularly castration-resistant prostate cancer. These treatments work by blocking the activity of male hormones such as testosterone (androgens), which are implicated in the growth of prostate cancer cells. By disrupting the AR signaling pathway, these therapies aim to slow tumor progression and improve patient outcomes. Key therapeutic options include darolutamide, enzalutamide, (Xtandi, Pfizer / Astellas) and apalutamide (Erleada, Johnson and Johnson).
About Opaganib (ABC294640)
Opaganib, a first-of-its-kind proprietary investigational host-directed and potentially broad-acting orally administered drug 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).
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 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.
About ANZUP
ANZUP is the leading cancer-cooperative clinical trials group that brings together all of the professional disciplines and groups involved in researching and treating urogenital cancers and conduct high quality cancer research. ANZUP’s mission is to improve the lives of people affected by bladder, kidney, testicular, penile and prostate cancers towards our vision of living life without fear of cancer. ANZUP identifies gaps in evidence and areas of clinical need, collaborates with the best clinicians and researchers in genitourinary cancer and communicates frequently and effectively with the broader community along the way. ANZUP receives valuable infrastructure support from the Australian Government through Cancer Australia.
About Chris O’Brien Lifehouse and Ramsay Hospital Research Foundation
Chris O’Brien Lifehouse is a world-class not-for-profit, comprehensive cancer hospital based in Sydney, Australia. From screening to prevention, diagnosis, treatment and wellness, Chris O’Brien Lifehouse treats all types of cancer, specializing in those that are complex and rare, offering patients every service and therapy they need under one roof.
Ramsay Hospital Research Foundation was established in 2017 to enhance healthcare delivery and improve patient outcomes in Australia, guided by a mission to provide better outcomes for its patients, to investigate the diseases and illnesses which affect them and to progress the learning and development of those who care for them.