RedHill Pharma Ltd., a specialty biopharmaceutical company, today announced promising preliminary results from a preclinical study of opaganib, a novel orally administered selective inhibitor of sphingosine kinase 2 ( SK2), (administered at 250 mg / kg,) shows a reduction in thrombosis (blood clotting) in acute respiratory distress syndrome (ARDS) - a preclinical animal model for measuring thrombotic risks (blood clots).

These new findings indicate another important potential benefit of opaganib for COVID-19 patients - in addition to the already established inhibition of SARS-CoV-2 replication and the potential reduction in the hyperimmune response by opaganib. Based on these preliminary findings, further work is planned to assess the range of potential physiologically and pharmacologically relevant opaganib doses with regard to thrombosis reduction.

“Acute Respiratory Distress Syndrome (ARDS) is one of the greatest dangers of COVID-19. Patients with severe COVID-19 courses are at increased risk of potentially fatal venous thrombosis and pulmonary embolism. There are currently very limited options available to clinicians that we know will be effective against ARDS, and ARDS-induced thrombosis in particular, " said Reza Fathi , PhD., Senior VP of Research and Development at RedHill.

“The results of our study show that opaganib 250 mg / kg decreases blood clot length, weight and total thrombus score in a preclinical ARDS model. Added to this are the well-known antiviral and anti-inflammatory activities of opaganib, which offers the potential for a unique triple-action effect on the pathophysiological processes associated with COVID-19. Opaganib, which targets a host cell component, may minimize the likelihood of resistance due to viral mutations. Before the endThis month we expect clinical insights into the safety and potential efficacy signals of opaganib from the non-commercial US phase II study in which the final patient received his final dose on November 26th. This is to be followed by the first data from the larger global phase II / III study in the first quarter of 2021, which is designed for efficacy and for which enrollment is already 60% complete. "

“The ARDS thrombosis model on which this is based is validated and very meaningful. The results we have seen with opaganib are impressive and promising, " said Sebastien Labbe , PhD., Director, Translational Research at IPS Therapeutic Inc. who conducted the study." The results provide insight into an extremely high one desirable potential effect of opaganib in the treatment of patients with severe COVID-19 disease, whose prognosis is sometimes very poor. "

ARDS-induced thromboses can occur in up to a third of COVID-19 patients who require treatment in the intensive care unit and up to 9% of all hospital patients and are associated with a poor prognosis. The preclinical study is designed to evaluate the effectiveness of opaganib in reducing the incidence of adverse thromboembolic events in situ in the lipopolysaccharide (LPS) -induced model of pneumonia, a reliable ARDS model that mimics COVID-19 inflammation.

The results of the opaganib preclinical study are preliminary and were provided to the company by an independent third party following an initial independent analysis. They are still subject to additional review and analysis. Such review and analysis may produce results that are inconsistent with the results published in this press release and may not be repeated in future preclinical or clinical studies.

In a US Phase II study of opaganib in patients with severe COVID-19 pneumonia, enrollment of all 40 subjects was completed and the last patient received their final dose. The most important dates are expected this month. This phase II study is not focused on efficacy and focuses on evaluating safety and determining efficacy signals.

At the same time, recruitment for the 270-patient COVID-19 study with opaganib Phase II / III in patients with severe COVID-19 pneumonia is more than 60% complete. The study is approved in six countries and is expected to deliver initial results in the first quarter of 2021. This studyfocuses on effectiveness assessment. Recently, it was unanimously recommended by an Independent Data and Safety Monitoring Board (DSMB) to proceed after a pre-planned safety review of the first 70 patients treated for 14 days. The panel is expected to conduct a second preplanned safety review of the first 135 patients who met the primary endpoint this month. Later, a pre-planned, non-blinded interim analysis of the efficacy data from the same patients is carried out. The data remains blinded to the company.

Opaganib, a new chemical, is a proprietary, first-in-class, orally administered, selective sphingosine kinase-2 (SK2) inhibitor with a proven unique triple-action effect on the pathophysiological processes associated with COVID-19, the targets a host cell component of virus replication and potentially minimizes the risk of viral mutation resistance. Opaganib has also shown anti-cancer activity and can target multiple oncological, viral, inflammatory and gastrointestinal indications.

Preclinical data have shown both antiviral and anti-inflammatory activities of opaganib that have the potential to relieve inflammatory lung diseases such as pneumonia and to mitigate pulmonary fibrotic damage. Opaganib showed strong antiviral activity against SARS-CoV-2, the virus that caused COVID-19. Virus replication in an in vitro model of human lung bronchial tissue is completely inhibited. Preclinical in vivo studies have shown that opaganib lowers the death rate from influenza virus infections and improves lung injury caused by Pseudomonas aeruginosa by lowering IL-6 and TNF-alpha levels in bronchoalveolar irrigation fluids.

Opaganib, originally produced by the US company Apogee Biotechnology Corp. has successfully completed several preclinical studies with oncology, inflammation, digestive tract and radiation protection models as well as a phase I clinical study in cancer patients with solid tumours in advanced stage and an additional phase I study in multiple myeloma.

As part of a "compassionate use" program in Israel COVID-19 patients (classified according to the WHO ordinal scale) treated with opaganib in a leading hospital. Data from the treatment of these first patients with severe COVID-19 course with opaganib have already been published. Treatment outcome analysis suggests that patients treated with opaganib in a compassionate use program had significant benefits in both clinical outcomes and inflammatory markers compared to a retrospectively matched case-control group from the same hospital: All patients in the opaganib-treated group were discharged from hospital without intubation or mechanical ventilation, while 33% of the corresponding case-control group required intubation and mechanical ventilation.

Opaganib's development was supported by federal and state government grants and contracts awarded to Apogee Biotechnology Corp. awards, including by the NCI, BARDA, the US Department of Defense, and the FDA Office of Orphan Products Development.