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 in 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

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

TEL AVIV, Israel and RALEIGH, N.C., June 3, 2026 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced that it is actively discussing potential collaborations for advancement of its investigational oral drug, opaganib, to combat EVD, which can be fatal in approximately half of all cases⁷, including the World Health Organization's (WHO) SOLIDARITY CORE clinical trial platform and pharma collaborations.

Gilead Raday, Chief Operating Officer and Head of R&D at RedHill said: "Opaganib sits in a distinct category as a host-directed agent which can be added to direct-acting antivirals, representing an opportunity to enhance global infectious disease preparedness and biodefense infrastructure against EVD, while also being preferentially suited to the logistical challenges found on the ground during these tragic outbreaks."

Peer-reviewed published data shows opaganib's host-direction action stems from its ability to simultaneously inhibit three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS), altering the cellular lipid balance and enabling inhibition of replication of viruses like SARS-CoV-2 and Ebola. In EVD specifically, opaganib offers a potential dual mechanism of action; blocking the PI3K/Akt pathway critical for filovirus entry and suppressing NLRP3 inflammasome and reducing IL-6/TNFα and S1P-mediated vascular permeability (addressing immune dysregulation and vascular leak).

Proactively, and upon request, the Company has provided information to relevant government, industry and other organizations, regarding supply readiness and all available clinical and preclinical safety and efficacy data to aid rapid clinical and regulatory discussions.

Opaganib has demonstrated its safety and tolerability profile in more than 470 participants in multiple clinical studies and expanded access use, including a large global Phase 2/3 study in hospitalized patients with moderate to severe COVID-19, published in Microorganisms². Opaganib is an investigational new drug. It has not been approved by any regulatory authority and is not available for commercial distribution. Inclusion in the WHO CORE platform cannot be guaranteed.