RedHill Biopharma Provides Initial Update from its Opaganib COVID-19 Compassionate Use Program in Israel

Objective improvement in first two patients treated with opaganib in Israel who have demonstrated measurable clinical improvement within days of treatment initiation, including decreased supplemental oxygen requirements, decreased C-reactive protein (CRP) levels and increased lymphocyte levels
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One patient was treated in the ICU, was considered for intubation, and was released within days of treatment-initiation
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Opaganib was administered in addition to standard-of-care, including hydroxychloroquine background therapy, and was well tolerated
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Opaganib’s unique mechanism of action has both anti-viral and anti-inflammatory activities, targeting a critical host factor, minimizing potential development of resistance due to viral mutations  
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Compassionate use program approved in Italy with 160 patients planned to be treated; Discussions ongoing in the U.S. and other countries to increase the accessibility of opaganib under similar programs, as well as potential emergency clinical development programs

TEL-AVIV, Israel and RALEIGH, N.C., April 13, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, provided an initial update on the compassionate use program with its investigational drug, opaganib (Yeliva^®, ABC294640)¹, in patients with confirmed SARS-CoV-2 infection (COVID-19) in Israel.

The first two patients have been treated with opaganib at a leading hospital in Israel. At the time of treatment initiation, both patients suffered from moderate to severe acute respiratory symptoms related to SARS-CoV-2 infection, required supplemental oxygenation and were hypoxic despite being treated with maximum flow of oxygen with cannulas.

Preliminary findings from both patients demonstrated clinical improvement within days post treatment-initiation with opaganib. To date, both patients have shown decreased supplemental oxygen requirements and decreased C-reactive protein (CRP) levels, an important inflammatory biomarker correlated with lung lesions which could reflect disease severity². Both patients have also shown an increase in lymphocyte levels, a sign of improvement from virus-induced lymphopenia. One of the patients was being treated in the intensive care unit (ICU), was considered for intubation, and was released from the ICU within days of treatment initiation with opaganib.

Opaganib was administered to the hospitalized patients in addition to standard-of-care, which included hydroxychloroquine (HCQ) as background therapy. Opaganib was well tolerated at the doses administered and no opaganib-related treatment emergent adverse events have been reported to date.

“We are very encouraged by the preliminary findings showing clinical improvement in the first COVID-19 patients treated with opaganib, which further supports its safety and potential benefit to patients. Our hope is that the unique mechanism of action of opaganib, with both anti-viral and anti-inflammatory activity, will help COVID-19 patients by reducing lung inflammation, and thus preventing the disease from progressing to a stage which requires mechanical ventilation. Importantly, opaganib is targeting a critical host factor that the coronavirus is unlikely to evade via mutation in possible future outbreaks of the pandemic,” said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. “We are committed to expanding the availability of opaganib under compassionate use to additional hospitals and countries and are hopeful that this treatment could potentially benefit COVID-19 patients with life-threatening manifestations.”

In addition, approximately 160 patients are planned to be treated in three major hospitals in northern Italy under an expanded access program approved by the Italian National Institute for Infectious Diseases, allowing compassionate use of opaganib, for patients with confirmed SARS-CoV-2 infection with life-threatening manifestations.

To find out more about RedHill Biopharma's Expanded Access policy, please look here for additional information: www.redhillbio.com/expandedaccess.

Discussions are ongoing in the U.S. and other countries to increase the accessibility of opaganib under compassionate use program authorizations, as well as potential emergency clinical development programs.

A total of 131 subjects have been dosed with opaganib to date in ongoing and completed Phase 1 and Phase 2 clinical studies in oncology indications in the U.S., in pharmacokinetic studies in healthy volunteers in the U.S., and under the existing FDA-approved expanded access requests from physicians for individual oncology patients, establishing safety and tolerability in humans both in the U.S. and ex-U.S.

Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer, anti-viral and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. Pre-clinical data have demonstrated both anti-viral and anti-inflammatory activities of opaganib, with the potential to reduce lung inflammatory disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. Several prior pre-clinical studies support the potential role of SK2 in the replication-transcription complex of positive-strand single-stranded RNA viruses, similar to coronavirus, and its inhibition may potentially inhibit viral replication. Pre-clinical in vivo studies³ have demonstrated that opaganib decreased fatality rates from influenza-virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury.

Opaganib has undergone a Phase 1 clinical study in patients with advanced solid tumors and is currently being investigated, individually and in combination with hydroxychloroquine, in a Phase 1/2a study in advanced cholangiocarcinoma (bile duct cancer), and in a Phase 2 study in prostate cancer.

The development of opaganib has been supported by grants and contracts from U.S. federal and state government agencies awarded to U.S.-based Apogee Biotechnology Corp., including the U.S. National Cancer Institute (NCI), the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.

About Opaganib (ABC294640, Yeliva^®)
Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer, anti-viral and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. By inhibiting SK2, opaganib blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid-signaling molecule that promotes cancer growth and pathological inflammation. By inhibiting SK2, opaganib potentially blocks viral replication complex and pathological inflammation. Opaganib was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as a Phase 1 clinical study in cancer patients with advanced solid tumors. Opaganib received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma. Opaganib is also being evaluated for the treatment of coronavirus (COVID-19) in confirmed COVID-19 patients in Israel and is also planned to be evaluated in Italy. The development of opaganib has been supported by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including from the NCI, BARDA, the U.S. Department of Defense and the FDA Office of Orphan Products Development.

About RedHill Biopharma  
RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal diseases. RedHill promotes the gastrointestinal drugs Movantik^® for opioid-induced constipation in adults⁴, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults⁵ and Aemcolo^® for the treatment of travelers’ diarrhea in adults⁶. RedHill’s key clinical late-stage development programs include: (i) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (ii) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iii) RHB-102 (Bekinda^®), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (iv) Opaganib (Yeliva^®), a first-in-class SK2 selective inhibitor, targeting multiple oncology, inflammatory and gastrointestinal indications, with an ongoing Phase 1/2a study for cholangiocarcinoma; (v) RHB-106, an encapsulated bowel preparation, and (vi) RHB-107, a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. More information about the Company is available at www.redhillbio.com.