Biopharmaceutical company RedHill Biopharma Ltd (Nasdaq: RDHL) on Monday reported positive in vivo results showing that opaganib, when combined with venetoclax, reduced Chronic Lymphocytic Leukemia cell counts by 50% compared with controls, supporting its potential as an add-on therapy in venetoclax-resistant disease.

Data demonstrated significant reductions in CLL cells and lower CD3+, CD4+ and CD8+ T cell counts, alongside reduced PD1 expression in CD8+ cells. Findings align with prior research indicating overexpression of sphingosine kinase 2 in venetoclax-resistant cancer cells and suggest SPHK2 inhibition may resensitise resistant CLL cells.

Venetoclax, marketed as Venclexta and Venclyxto by AbbVie Inc and Genentech, is a first-in-class BCL-2 inhibitor approved in 2016 and generated approximately USD2.5bn in sales in 2024. Resistance to the therapy is an increasing clinical challenge despite combination treatment strategies.

Opaganib is a first-in-class oral SPHK2 inhibitor with a demonstrated safety and tolerability profile across more than 470 participants in clinical trials and expanded access programmes. Drug is under clinical evaluation in multiple indications, including a Phase 2 study in combination with darolutamide in advanced prostate cancer, and has received U.S. government support, including BARDA funding.

These results build on a growing body of preclinical oncology data supporting opaganib's therapeutic add-on potential and reinforce its broader development strategy across oncology, virology and inflammatory diseases.