RedHill's Opaganib Shows Promise in Neuroblastoma and Triple-Negative Breast Cancer Preclinical Studies
Key Insights
New preclinical data presented at the 2026 AACR Annual Meeting demonstrates that opaganib enhances the efficacy of oxaliplatin plus doxorubicin chemotherapy in high-risk neuroblastoma (search) by destabilizing n-Myc (search) oncogene.
A separate study shows opaganib pre-treatment followed by low-dose diABZI potentiates STING (search)-mediated effects and may augment anti-tumor immunity in triple-negative breast cancer (search) models.
Opaganib, a first-in-class oral sphingosine kinase-2 (search) inhibitor, has received FDA Orphan Drug and Rare Pediatric Disease designations for neuroblastoma (search) treatment.
RedHill Biopharma announced promising preclinical data for opaganib (ABC294640) at the 2026 American Association for Cancer Research (AACR) Annual Meeting, demonstrating potential therapeutic benefits in two challenging cancer types: neuroblastoma (search) and triple-negative breast cancer (search).
Neuroblastoma Combination Therapy Shows Enhanced Efficacy
Independent research conducted by Penn State University's Jeremy Hengst, PhD, and Apogee Biotechnology, funded by the Beat Childhood Cancer Foundation and Four Diamonds, revealed that opaganib may significantly enhance the therapeutic efficacy of the oxaliplatin plus doxorubicin (OXDOX) chemotherapy combination in high-risk neuroblastoma (search).
The study demonstrated that opaganib directly destabilizes n-Myc (search), a key oncogenic driver of neuroblastoma (search) and other solid tumors that regulates cell proliferation, differentiation, and apoptosis during embryonic development. This destabilization occurs through increased ceramide production, which enhances programmed cell death (apoptosis) in cancer cells.
Neuroblastoma (search) represents a significant unmet medical need, being the most common infancy cancer with approximately 5,500 global pediatric cases per year in children aged 0-14. The disease accounts for 10% of childhood cancers and 15% of pediatric cancer-related deaths in the United States.
Triple-Negative Breast Cancer Immunity Enhancement
A second poster from the University of Kansas' Colette Worcester described in vitro model data showing that pre-treatment with opaganib, followed by low-dose diABZI treatment, potentiated downstream STING (search)-mediated effects and may augment anti-tumor immunity in triple-negative breast cancer (search) (TNBC). TNBC has the poorest prognosis among breast cancer subtypes, making these findings particularly significant for addressing this challenging malignancy.
Regulatory Recognition and Clinical Development
Opaganib has received FDA Orphan Drug and Rare Pediatric Disease designations for neuroblastoma (search) treatment, with potential for a Rare Pediatric Disease Priority Review Voucher. Development discussions for this indication are ongoing with Penn State University and the Beat Childhood Cancer consortium.
Dr. Mark Levitt, Chief Scientific Officer at RedHill, commented on the findings: "These data represent exciting findings that could hold promise for improving outcomes in treating pediatric NB and TNBC, providing additional encouragement for further exploration. Opaganib has previously shown potential as add-on therapy in several preclinical oncology models in combination with chemotherapy."
Mechanism of Action and Safety Profile
Opaganib is a proprietary first-in-class investigational, orally administered sphingosine kinase-2 (search) (SPHK2) selective inhibitor drug. The compound works through the inhibition of multiple pathways implicated in various disease processes, including simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).
The drug has demonstrated its safety and tolerability profile in more than 470 people across multiple clinical studies and expanded access use, including a large global Phase 2/3 study in hospitalized patients with moderate to severe COVID-19.
Ongoing Clinical Programs
Currently, a Bayer (search)-supported 80-patient placebo-controlled randomized Phase 2 study is ongoing to evaluate the efficacy of opaganib in combination with Bayer's darolutamide in men with metastatic castrate-resistant prostate cancer (search) (mCRPC). This study is testing the potentially enhancing effect of opaganib in patients with a poor prognosis.
Dr. Levitt noted that "the ongoing Phase 2 clinical study of opaganib in combination with darolutamide in advanced prostate cancer could potentially provide paradigm-shifting clinical data in support of the additive use of opaganib in a cancer setting."
Opaganib also has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma (search) and has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.