Amid the rapidly evolving Ebola virus disease (EVD) outbreak involving the rare Bundibugyo ebolavirus sub-type, for which there are no approved medications or vaccines, RedHill Biopharma is actively discussing potential collaborations for clinical advancement of opaganib1, including the World Health Organization's (WHO) SOLIDARITY CORE clinical trial platform

Opaganib EVD rationale (analogous to EVD treatment pathway):

  • Phase 3 clinical antiviral activity (severe COVID-19) showing2:
    • 70.2% mortality reduction with opaganib given as add-on to best available standard of care (remdesivir + corticosteroids): 6.98% (n=3/43) opaganib + SoC vs. 23.4% (n=11/47) placebo + SoC (p=0.034))
    • Improved median time to viral RNA clearance by ≥4 days in opaganib-treated patients (median 10 days vs. not reached by Day 14 in placebo, HR 1.34, p=0.043)
    • Demonstrated safety and tolerability profile in 470 clinical trial participants
  • Preclinical EVD activity (United States Army Medical Research Institute of Infectious Diseases (USAMRIID)-funded studies showed3:
    • Opaganib inhibition of EVD in human macrophages
    • Increased survival for opaganib group (one of two animal models)4
    • Synergistic effect when opaganib combined with Gilead Sciences' remdesivir (Veklury®)
  • Opaganib's potential dual mechanism of action against EVD and filovirus-class activity5:
    • Opaganib's therapeutic target—SPHK2 inhibition—disrupts host-cell components essential for filovirus entry and replication that are conserved across Filoviridae
    • PI3K/Akt pathway inhibition (required for filovirus entry and membrane trafficking)
    • NLRP3 and IL-6/TNFα inflammasome suppression and S1P-mediated vascular permeability reduction (addressing immune dysregulation and vascular leak in viral hemorrhagic fever)
    • Published literature explicitly validates sphingosine kinases as targets for filovirus inhibition6
  • Opaganib, an investigational SPHK2 inhibitor drug, offers a novel potential approach to strengthen global infectious disease preparedness and biodefense:
    • Host-directed therapeutic (HDT) – providing for a possible two-pronged approach to viral defense with potential for co-administration with direct-acting EVD-focused antivirals (i.e. Gilead's remdesivir and obeldesivir, Regeneron's maftivimab, and Mapp's MBP134) with minimal expected drug-drug interactions
    • Oral administration, ease of storage and distribution supporting clinical evaluation and possible stockpiling requirements

With the WHO suggesting the current outbreak was outpacing response efforts7, the Company has provided available supply readiness, safety and efficacy data to aid rapid discussions to enable clinical exploration of the potential synergies of opaganib host-directed therapy in addressing a growing global public health threat