RedHill Biopharma Ltd. , a specialty biopharmaceutical company, announced today that preliminary data first-line studies from their US phase 2 study of orally administered opaganib (Yeliva®, ABC294640) [1] in hospitalized patients with COVID-19 pneumonia demonstrated positive signs of safety and efficacy.

The US Phase 2, randomized, double-blind, placebo-controlled, proof-of-concept study with opaganib ( NCT04414618 ) enrolled 40 patients requiring oxygen support. The study was not driven by statistical significance and was aimed at assessing safety and identifying preliminary signs of activity. Patients in the study were randomly selected in a 1: 1 ratio to receive either opaganib or placebo in standard of care (SoC) and followed up to 42 days after initiation of treatment.

• The first-line results of the study found that opaganib is safe, with no material safety differences between the opaganib and placebo treatment arms. Overall, fewer patients suffered from serious adverse events (SAEs) in the opaganib treatment arm than in the placebo arm. In this small sample size, there were few intubation or fatality events and these were balanced between the two arms.
• The opaganib arm demonstrated a consistent trend of greater improvement in the reduction of oxygen requirements at the end of treatment on day 14 across the main primary and secondary efficacy outcomes, correlating with clinical improvement as defined by the Ordinal scale of the World Health Organization (WHO):

- A greater improvement in the proportion of patients taking room air and no longer requiring oxygen support by day 14 compared to the control arm (52.6% vs 22.2%).

- A greater improvement in the proportion of patients with a 50% reduction in supplemental oxygen on day 14 versus the control arm (89.5% versus 66.7%).

- A higher proportion of patients discharged on day 14 compared to the control arm (73.7% vs 55.6%).

- A greater reduction from the start of the mean total oxygen requirement (AUC) for 14 days compared to the control arm (68.0% vs 46.7%).

A full data analysis, including viral and inflammatory biomarker analyzes, baseline risk factors, and background therapy stratifications of SoC, is expected in the coming weeks. The Company will provide the data for peer review when available.

"We are pleased with these encouraging first-line results from our exploratory Phase 2 study that confirm the safety of opaganib and demonstrate promising signs of activity when treating COVID-19 patients requiring oxygen support. These preliminary results support our study. Ongoing Phase 2/3 Global Severe Pneumonia from COVID-19, which is expected to occur in the first quarter of 2021. We are continuing to work diligently to compile a robust dataset to support potential global applications for emergency, " said Mark L. Levitt , MD, Ph.D., medical director at RedHill .

Gilead Raday , RedHill's  Chief Operating Officer , added: "Opaganib has a unique dual mode of action that is anti-inflammatory and antiviral - acting on both the cause and effects of COVID-19. Opaganib targets sphingosine kinase-2. , a human cellular component involved in viral replication and not the virus itself. Increasing evidence of new SARS-CoV-2 mutations emerging globally underscores the importance of this unique mechanism, which potentially minimizes the risk of viral resistance to therapy. Patient improvement trends shown by preliminary first-line data support the ongoing Phase 2/3 study with opaganib, which will provide a deeper understanding of opaganib activity. "

The efficacy of opaganib in severe COVID-19 pneumonia is being further explored in an ongoing global phase 2/3 study and a first-line data report is expected in the first quarter of 2021. This study ( NCT04467840 ) is being carried out at approximately 30 clinical sites in various countries and is on track to enroll up to 270 patients. The study has undergone two unblinded reviews of the safety data by an independent Data and Safety Monitoring Board (DSMB), with unanimous recommendations to continue the study. An interim analysis of the futility of the DSMB will be conducted in the coming weeks, evaluating the data from the first 135 subjects who have reached the primary variable.

The first-line results of the US phase 2 study of opaganib in hospitalized patients with COVID-19 pneumonia are preliminary and were provided to the Company by an independent third party after initial independent analysis and remain subject to review and analysis. additional. Such review and analysis may lead to findings inconsistent with the results disclosed in this release and cannot be replicated in future studies.

About Opaganib (ABC294640, Yeliva ® )

Opaganib, a new chemical entity, is a novel selective sphingosine kinase 2 (SK2) inhibitor that is administered orally, with a unique demonstrated effect of dual anti-inflammatory and antiviral activity that targets a component of the host cell of the viral replication, potentially minimizing the likelihood of viral resistance. Opaganib has also shown anti-cancer activity and has the potential to target multiple oncological, viral, inflammatory, and gastrointestinal indications.

Opaganib received orphan drug designation from the United States Food and Drug Administration (FDA) for the treatment of cholangiocarcinoma and is being evaluated in a phase 2a study for patients with advanced cholangiocarcinoma and in a phase 2 study for patients. with prostate cancer. Opaganib is also being evaluated as a treatment for COVID-19 pneumonia in a global Phase 2/3 study and has shown positive signs of safety and efficacy in preliminary first-line data from a Phase 2 US study.

Preclinical data have demonstrated anti-inflammatory and antiviral activities of opaganib with the potential to reduce inflammatory disorders of the lung, such as pneumonia, and to mitigate fibrotic lung damage. Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, through total inhibition of viral replication in an in vitro model   of human bronchopulmonary tissue. Additionally, in vivo preclinical studies  [2]  have shown that opaganib reduces the fatality rate from influenza viral infection and improves lung damage induced by  Pseudomonas aeruginosa  by reducing the levels of IL-6 and TNF-alpha in fluids. bronchoalveolar irrigation.

Opaganib was originally developed by Apogee Biotechnology Corp. in the United States and completed multiple successful preclinical studies in oncology, inflammatory, gastrointestinal, and radioprotective models, as well as a phase 1 clinical study in cancer patients with advanced solid tumors and a phase study 1 additional in patients with multiple myeloma.

The development of opaganib has been supported by grants and contracts from United States federal and state government agencies, awarded to Apogee Biotechnology Corp., including the NCI, BARDA, and the Department of Defense and FDA's Office for the Development of Orphan Products of the United States.

Ongoing studies with opaganib are registered at  www.ClinicalTrials.gov , a web service of the US National Institutes of Health, which provides public access to information on publicly and privately funded clinical trials.   

About RedHill Biopharma

RedHill Biopharma Ltd. (Nasdaq: RDHL ) is a specialized biopharmaceutical company focused primarily on gastrointestinal and infectious diseases. RedHill promotes gastrointestinal medications,  Movantik ®  for opioid-induced constipation in adults with non-cancerous pain [3] ,  Talicia ®  for the treatment of  Helicobacter pylori (H. pylori) infection  in adults [4]  and  Aemcolo ®  for the treatment of traveler's diarrhea in adults [5] . RedHill's key late-stage clinical research programs under development include the following: (i)  RHB-204, with an ongoing phase 3 study for nontuberculous mycobacterial (NTM) lung infections; (ii)  opaganib (Yeliva ® ) , a first of its kind selective SK2 inhibitor targeting multiple indications with a phase 2/3 program for COVID-19 and phase 2 studies for prostate cancer and cholangiocarcinoma underway; (iii)  RHB-104 , with positive results from a first phase 3 study for Crohn's disease; (iv)  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; (v)  RHB-107  ( upamostat), a phase 2 serine protease inhibitor of its kind targeting cancer and inflammatory gastrointestinal diseases and is also being evaluated for COVID-19 and (vi)  RHB - 106 , an encapsulated gut preparation. In  www.redhillbio.com  be available more information about the company.

NOTE: This press release, presented for your convenience, is a translated version of the official press release published by the company in the English language. To read the full press release in English, including the statement disclaimer, visit:  https://ir.redhillbio.com/press-releases .

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Company Contact:

Adi Frish
Corporate and Business Development Director  
RedHill Biopharma
+ 972-54-6543-112
adi@redhillbio.com

Media Contact (US):

Bryan Gibbs
Vice President
Finn Partners
+ 1-212-529-2236
bryan.gibbs@finnpartners.com

1.  Opaganib is an investigational new drug, not available for commercial distribution.

2. Xia C. et al. Transient inhibition of sphingosine kinases confers protection to influenza A virus infected mice. Antiviral Res. 2018 Oct; 158: 171-177. Ebenezer DL et al. Pseudomonas aeruginosa stimulates nuclear sphingosine-1-phosphate generation and epigenetic regulation of lung inflammatory injury. Thorax. 2019 Jun; 74 (6): 579-591.

3.  Complete prescribing information for Movantik ® (naloxegol) available at: www.Movantik.com .

4. Complete prescribing information for Talicia ® (omeprazole magnesium, amoxicillin and rifabutin) available at: www.Talicia.com .

5.  Complete prescribing information for Aemcolo ® (rifamycin) available at: www.Aemcolo.com .

 

Source: prnewswire.com

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