Opaganib - RedHill Biopharma
Alternative Names: ABC-294640; YELIVALatest Information Update: 23 Feb 2024
At a glance
- Originator Apogee Biotechnology Corporation
- Developer Apogee Biotechnology Corporation; Medical University of South Carolina; RedHill Biopharma; University of Louisville
- Class Adamantanes; Amides; Anti-inflammatories; Antineoplastics; Antirheumatics; Antithrombotics; Antivirals; Chlorobenzenes; Pyridines; Small molecules
- Mechanism of Action Sphingosine kinase inhibitors
-
Orphan Drug Status
Yes - Cholangiocarcinoma
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
- Available For Licensing Yes - Cancer; Inflammation
Highest Development Phases
- Phase II/III COVID-19 pneumonia
- Phase II Cholangiocarcinoma; Prostate cancer
- Preclinical Acute radiation syndrome; COVID 2019 infections; Ebola virus infections; Influenza A virus infections; Radiation injuries; Renal fibrosis; SARS-CoV-2 acute respiratory disease
- Suspended Liver cancer
- No development reported Cancer; Inflammatory bowel diseases; Osteoarthritis; Rheumatoid arthritis; Solid tumours
- Discontinued Multiple myeloma
Most Recent Events
- 20 Feb 2024 Pharmacodynamic data from the preclinical study in acute radiation syndrome released by RedHill Biopharma
- 20 Dec 2023 Pharmacodynamics data from a preclinical study in Ebola virus infections released by RedHill Biopharma
- 03 Oct 2023 Preclinical trials in Ebola virus infections in USA prior to October 2023 (PO)
Development Overview
Introduction
Opaganib is an orally available small molecule inhibitor of sphingosine kinase-2 (SPHK-2), being developed by RedHill Biopharma, for the treatment of cancer, COVID-2019 infections, COVID-19 pneumonia, Ebola virus infections, renal fibrosis, acute radiation syndrome, and other inflammatory and gastrointestinal indications. The drug blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation, by inhibiting SPHK-2. The preclinical data and literature also indicates anti-viral activity of the molecule. SK-2 plays a vital role in the replication-transcription complex of positive-strand single-stranded RNA viruses, similar to SARS-CoV-2, and its inhibition could potentially inhibit viral replication. Opaganib also targets the downstream inflammatory/immune responses. Phase II/III clinical development for COVID-19 pneumonia is underway in the US, Brazil, Mexico, Switzerland, Russia, Italy, Israel, Peru, Poland, Colombia and the UK. Phase II clinical development is underway for cancer, including cholangiocarcinoma, and prostate cancer in the US. Preclinical development for SARS-COV-2 acute respiratory disease, COVID-2019 infections, influenza A virus infections,renal fibrosis, inflammatory-bowel-disease, osteoarthritis,rheumatoid arthritis, cancer, radiation injuries and acute radiation syndrome is underway in the US and Israel.
RedHill Biopharma is prioritizing opaganib for the treatment of acute radiation syndrome [1] .
Opaganib was originally developed by Apogee Biotechnology Corporation and was subsequently acquired by RedHill Biopharma.
RedHill is pursuing and evaluating multiple clinical programs in oncology, inflammatory and gastrointestinal indications, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate opaganib as an add-on therapy to their existing oncology treatments.
As of December 2016, phase I/II ABC 103 trial for multiple myeloma was underway in the US, however as of April 2023, the company announced that it had no further intention to pursue the development of opaganib for multiple myeloma, hence the development was discontinued. Phase I development for solid tumours and preclinical development for inflammatory-bowel-disease, osteoarthritis, and rheumatoid arthritis was underway in the US. However, no recent reports of development have been identified. As at October 2020, no recent reports of development had been identified for clinical-Phase-Unknown development in Cancer (Combination therapy) in USA (PO, Capsule). In September 2019, a phase II trial in hepatocellular carcinoma (liver cancer in the development table) was suspended as it is being rewritten for different disease population.
Company Agreements
In February 2023, RedHill Biopharma and the National Institute of Allergy and Infectious Diseases' Radiation and Nuclear Countermeasures Program (RNCP) have chosen opaganib for the nuclear medical countermeasures product development pipeline as a potential treatment for Acute Radiation Syndrome (ARS). Contractors led and financed by the RNCP will conduct studies planned in partnership with RedHill to test opaganib in proven ARS models as part of this agreement. [2]
In March 2022, RedHill Biopharma and Kukbo entered into a licensing agreement for opaganib to treat patients with COVID-19, in South Korea. As part of the license agreement, RedHill Biopharma will receive an upfront payment of $US1.5 million and will be eligible to receive milestone payments of up to US5.6 million plus low double-digit royalty payments on net sales of oral opaganib in South Korea. Opaganib will be exclusively sold in Korea by Kukbo for COVID-19. In September 2022, the Redhill filed a lawsuit against Kukbo, as a result of Kukbo's default in delivering to the Company $US5.0 million under the Subscription Agreement, dated October 25, 2021, in exchange for ADSs, and a further payment of $US1.5 million due under the Exclusive License Agreement, dated March 14, 2022. Kukbo has not raised counter arguments and we believe a favorable judgement is expected within weeks, strengthening the balance sheet significantly if collected [3] . [4]
In February 2021, RedHill Biopharma expanded the manufacturing agreement with Cosmo Pharmaceuticals to expand manufacturing capacity of Clarithromycin/clofazimine/rifabutin combination therapy (RHB-204) and Naloxegol (Movantik®). In January 2021, RedHill Biopharma entered a manufacturing agreement with Cosmo Pharmaceuticals to expand manufacturing capacity of opaganib to address demand subsequent to potential global emergency use authorisations. [5] [6] [7]
In October 2020, RedHill Biopharma entered into agreement with an undisclosed manufacturing company in Europe. The agreement will help build up the manufacturing of opaganib to support the potential emergency use applications for patients with COVID-2019 infections. Financial terms were not disclosed. [8]
In October 2020, RedHill Biopharma entered into agreement with an undisclosed manufacturing company in Canada. The agreement will help build up the manufacturing of opaganib to support the potential emergency use applications for patients with COVID-2019 infections. Financial terms were not disclosed.
In September 2016, RedHill Biopharma entered into a research collaboration with Stanford University School of Medicine to evaluate planned phase Ib clinical study to evaluate opaganib as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy. Stanford will evaluate the effect of opaganib on mucositis reduction and tumour control in a murine model of head and neck cancer as part of the collaboration [9] .
In October 2015, RedHill BioPharma announced that National Cancer Institute awarded a Small Business Innovation research (SIBR) grant of US$225 000 to the company to support a preclinical study of opaganib for the treatment of prostate cancer [10] .
National Cancer Institute awarded a Small Business Innovation Research grant of US$2 million to RedHill BioPharma, in September 2015, to support a phase II study of opaganib in patients with multiple myeloma. The grant covers a three year period and was awarded in conjunction with Duke University [11] .
In March 2015, RedHill Biopharma entered into an agreement with Apogee Biotechnology Corporation. Under the terms of the agreement, RedHill acquired the exclusive worldwide rights to the commercialisation, development and addition IP rights of opaganib for all indications. RedHill has agreed to pay $US1.5 million and an additional $US4 million to Apogee as potential milestone payments and royalties [12] .
In August 2011, the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) issued new contracts funds ($US2 million over 2 years), which will be used to conduct preliminary studies of opaganib for reduction of gastrointestinal injury caused by acute radiation exposure [13] .
Key Development Milestones
Cholangiocarcinoma
In April 2017, RedHill Biopharma announced that the US FDA has granted opaganib Orphan Drug designation for the treatment of cholangiocarcinoma [14] .ID
In January 2018, RedHill Biopharma initiated an expanded access programme of opaganib for patients with cholangiocarcinoma who do not qualify for participation in ABC-108 study (ABC-108-EA; NCT03414489). In September 2018, RedHill Biopharma announced that a patient enrolled in the US under this programme achieved a confirmed complete response as measured by RECIST criteria [15] .
In June 2022, RedHill Biopharma, in collaboration with Mayo Clinic, University of Utah and the University of Texas MD Anderson Cancer Center, completed a phase IIa trial that investigated opaganib as a monotherapy, for the treatment of patients suffering from advanced, unresectable, intrahepatic, perihilar and extrahepatic cholangiocarcinoma (ABC-108; NCT03377179). The open-label trial was initiated in March 2018, and enrolled 65 patients with no more than two systemic anti-neoplastic therapy, in the US. In April 2018, first five patients were enrolled in the trial. In September 2018, RedHill Biopharma reported that the trial met its pre-specified efficacy endpoint of either partial or complete response or stable disease at four months. In March 2020, the company reported that a second arm of the study, assessing opaganib, in combination with hydroxychloroquine sulfate, had been added and recruitment of patients initiated. Redhill Biopharma also added a third arm to the study, evaluating opaganib in combination with upamostat [see Adis Insight Drug Profile 800021537], subject to discussions with the US FDA. In November 2020, enrolment had been completed for the first cohort of 39 patients, evaluating the activity of opaganib as a stand-alone treatment. Preliminary data from this cohort demonstrated a signal of activity in a number of subjects with advanced cholangiocarcinoma [16] [17] [18] [19] [20] [21] .
In November 2022, Data from preclinical studies was presented at 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD-2022) [22] .
In June 2020, RedHill Biopharma presented pharmacodynamics data from a preclinical study in cholangiocarcinoma at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [23] .
As of November 2020, preclinical findings demonstrated that treatment with opaganib and upamostat in combination resulted in tumour regression [20] .
In preclinical studies conducted in patient derived cholangiocarcinoma cell lines, ABC294640 reduced proliferation and survival of the cancer cells by inhibiting STAT3 phosphorylation pathway, by inducing autophagy and by inducing apoptosis. ABC294640 was shown to act synergistically with sorafenib, which resulted in further inhibition of proliferation [24] .
COVID-19 pneumonia and COVID-2019 infections
As of November 2022, discussions with the US government are ongoing for pandemic preparedness and other government programs, both opaganib and RHB 107 demonstrated in vitro inhibition of Omicron BA.5 sub-variant. Opaganib demonstrated in vitro efficacy against influenza, Ebola, and others. In November 2022, Redhill Biopharma released results from in vitro studies [3] .
In November 2021, Redhill Biopharma submitted data packages for opaganib in the treatment of COVID-2019 infections to regulators in various territories including the US, EU, UK and others, ahead of planned regulatory advice [25] . As of April 2022, regulatory submissions and discussions in the U.S., Europe, UK and additional countries are progressing regarding confirmatory data requirements and pathways to potential approval [26] .
In December 2021, RedHill Biopharma announced that opaganib is expected to be unaffected by mutations associated with Omicron and other known variants of concern as the opaganib's proposed mechanism of action is not impacted by spike protein mutations [27] .
In August 2021, Redhill Biopharma announced that, company is discussing with the FDA, EMA and other regulators for potential pathways to marketing approval, regulatory path submissions including potential submissions of emergency use applications in those countries, as well as the specific requirements in each country for the approval of opaganib in the treatment of COVID-2019 infections [28] .
In August 2021, RedHill Biopharma announced that, Quantum Leap Healthcare Collaborative and the U.S. government's Biomedical Advanced Research and Development Authority (BARDA) are close to selection of opaganib for inclusion in the I-SPY COVID-19 Trial, with funding for opaganib provided by BARDA [28] .
In August 2021, Redhill Biopharma initiated a Compassionate Use Programme to provide opaganib treatment on an outpatient basis under for patients suffering from COVID-19 pneumonia in Switzerland [29] .
In September 2021, Redhill Biopharma announced that phase II/III trial in patients with COVID-2019 pneumonia did not meet its primary endpoint (ABC-201; NCT04467840; EudraCT202000267795). Analysis of the study efficacy endpoints did show trends in favor of the opaganib compared to placebo across multiple endpoints, including primary end point, however statistical significance was not achieved [30] . In July 2021, trial was completed evaluating the efficacy of opaganib, in addition to standard-of-care therapy, in patients hospitalised with severe COVID-19 pneumonia. The primary endpoint of the trial was the proportion of patients reaching room air (no longer requiring oxygen supplementation) by day 14. The randomised, double-blind, parallel-arm, placebo-controlled trial was initiated in July 2020 and in June 2021 the study completed enrollment of 475 patients in Brazil, Colombia, Israel, Italy, Mexico, Poland, Peru, Russia, the UK and the US [31] [32] . In February 2021, Redhill Biopharma announced its plans to expand the global phase II/III study of opaganibin in patients with severe COVID-19 pneumonia to the US, following US FDA's review of the data from the phase II trial of opaganib and receipt of its recommendations [33] [34] . In April 2021, RedHill Biopharma completed enrollment of over 75% (255 patients) of the targeted 464 patients globally and announced that the Independent Data and Safety Monitoring Board (DSMB) unanimously recommended for the fourth time to continue the trial in severe COVID-19 pneumonia patients. The recommendation was based on an analysis of unblinded safety data from the first 255 patients treated for 14 days, extending the total opaganib safety database to approximately 380 patients [35] [36] [37] [38] [39] [40] [41] . In May 2021, the company announced that patient enrolment in the trial is almost 100% complete [42] . In July 2021, RedHill Biopharma announced completion of all treatments and patient follow-ups of phase II/III trial of opaganib in COVID-19 pneumonia in 475 patients [43] [31] . In August 2020, Redhill Biopharma received an approval from the Mexican Federal Committee for the Protection against Sanitary Risks (COFEPRIS) for clinical trial authorization (CTA) application to commence the phase II/III trial, followed by the approval from the Brazilian Health Regulatory Agency, in September 2020 [44] [45] . The same was also approved by the Ministry of Health of the Russian Federation in July 2020 and the UK Medicines & Healthcare products Regulatory Agency (MHRA) in June 2020, respectively [46] [47] . Earlier the company initiated CTA submission with the Brazilian Health Regulatory Agency (ANVISA) and Italian Medicines Agency (AIFA) for initiation of a phase II/III study in patients hospitalized with severe SARS-CoV-2 infection (the cause of COVID-19) and pneumonia [48] [49] . In July 2021, the company announced continuation of patient enrollment in the trial and also reported that it has recently received a positive DSMB futility review [50] [51] . Later in October 2021, safety and efficacy data from this trial were released by the Redhill Biopharma [52] [53] . In July 2022, company released the efficacy data from the trial [54] .
In December 2020, RedHill Biopharma completed a phase IIa trial that assessed the safety and efficacy of opaganib in patients hospitalised with severe COVID-19 positive pneumonia (NCT04414618; ABC-110). Earlier, in June 2020, RedHill Biopharma initiated the non-powered, proof of concept trial. The randomised, double-blind, placebo-controlled trial completed enrolment of 42 patients in the US and Israel, in November 2020. In December 2020, the company announced positive top-line results from the trial. The IND application for the same submitted in April 2020 was approved by the US FDA in May 2020. In August 2020, the trial successfully passed the first independent Safety Monitoring Committee (SMC) review. The SMC reviewed unblinded safety data from the first 12 patients treated for at least seven days, recommending that the study continue without change. In September 2020, the trial passed its second safety review by the independent Safety Monitoring Committee (SMC) with a unanimous recommendation to continue the study without change. The SMC’s recommendation was based on an unblinded analysis of safety data from the first 24 patients treated in the study for at least seven days. In April 2020, RedHill Biopharma submitted an IND application of opaganib to the US FDA for the treatment of pneumonia. In June 2021, RedHill Biopharma released efficacy and safety data from this study. In June 2021, data from the trial were presented at World Microbe Forum 2021 (ASM-FEMS-WMF-2021) [55] [56] [57] [58] [37] [38] [45] [46] [49] [59] [60] [61] [41] [20] [62] .
Owing to the replacement with a randomised placebo-controlled study, in August 2020, Redhill Biopharma withdrew the phase I/II Opaganib-RHB trial prior to enrolment.The open-label trial was trial was designed to evaluate the efficacy of opaganib in COVID-2019 patients with pneumonia requiring oxygen but not mechanical ventilation in Israel (NCT04502069; ABC-112) [63] .
In July 2020, the Israeli Ministry of Health approved a clinical trial application to initiate a study evaluating opaganib in up to 50 patients with severe COVID-19 infection and pneumonia [46] .
As at April 2020, the compassionate use programme for COVID-2019 infections is ongoing in Israel, with first patient dosed with opaganib in addition to standard-of-care hydroxychloroquine as background therapy. In the same month, RedHill Biopharma released efficacy and adverse events data obtained from the trial in COVID-2019 infections. The company announced that six patients have been treated and also reported that two patients safely completed 14 days of opaganib therapy, in April 2020. All six patients analysed were weaned from oxygen and discharged from the hospital [59] [64] [65] [66] [67] [68] . In June 2020, the company released the updated efficacy and safety data from five patients with severe COVID-19 infections [69] . In June 2019, data from the programme were published in Antiviral Research [70] .
In April 2020, the Italian National Institute for Infectious Diseases and Central Italian Ethics Committee (EC) for an expanded access program (EAP) approved the immediate compassionate use of opaganib in patients with COVID-2019 infection in Italy [67] .
In April 2022, Redhill Biopharma release preclinical data that showed strong inhibition by opaganib against omicron variants [26] .
In August 2021, Redhill Biopharma released preliminary results from preclinical study that showed strong inhibition by opaganib of delta variant replication while maintaining cell viability at relevant concentrations [71]
In preclinical studies, conducted by Redhill Biopharma in collaboration with the University of Louisville Center for Predictive Medicine in a 3D tissue model of human bronchial epithelial cells (EpiAirway™), opaganib demonstrated potent inhibition of both the Beta (South African) and Gamma (Brazilian) SARS-CoV-2 variants at non-cytotoxic doses [72] .
In September 2020, RedHill Biopharma announced that in preclinical studies, opaganib showed potent activity compared to all compounds tested, including remdesivir. There was dose dependent inhibition of virus production without compromising cell membrane integrity. The company intends to receive emergency use authorisation (EUA) for COVID-19 infections. Discussion were ongoing with the US government agencies for potential emergency use approval [73] [70]
In March 2020, RedHill Biopharma reported that based on pre-clinical data and literature indicating potential anti-viral activity, the company is actively pursuing an exploratory program intended to investigate the activity of opaganib and upamostat [see Adis Insight Drug Profile 800021537], individually and in combination with hydroxychloroquine and other compounds in the treatment of COVID-2019 (novel coronavirus) [19] .
In October 2022, Redhill Biopharma released preclinical data of Opaganib in COVID-19 infection [74] .
In January 2021, preclinical data from in vitro studies in COVID-2019 infections released by the company [5] .
As of September 2020, opaganib had demonstrated potent antiviral activity against SARS-CoV-2, completely inhibiting viral replication, as measured after three days incubation, in an in vitro model of human lung bronchial tissue, comparing favourably with remdesivir, the positive control in the study. Furthermore, treatment of cells infected with SARS-CoV-2 with opaganib did not compromise cell membrane integrity [70] [20] [52] .
Ebola virus infections
In October 2023, results from an in vivo study sponsored by US Army were released by RedHill Biopharma. Opaganib also showed in vitro benefit in several strains of Ebola virus disease models [75] .
In December 2023, pharmacodynamics data from preclinical studies in Ebola virus infections released by RedHill Biopharma [76]
Hepatocellular Carcinoma (HCC)
In September 2019, Apogee Biotechnology and Medical University of South Carolina (MUSC) withdrew a phase II ABC-106 trial prior to enrolment as the trial is being rewritten for different disease population. The trial was withdrawn and replaced with phase II ABC 107 trial in prostate cancer. In October 2016, RedHill Biopharma in collaboration with Apogee Biotechnology and MUSC, announced the initiation of the phase IIa trial to evaluate the safety and efficacy of opaganib, in patients with advanced hepatocellular carcinoma (liver cancer in the development table) who have tumour progression following sorafenib treatment in the US(102418; ABC-106; NCT02939807) [77] [78] [79] . The trial was supported by a $US1.8 million grant from the NCI awarded to MUSC (1P01CA203628-01) [80] [81] [82] .
Prostate cancer
In March 2020, Medical University of South Carolina (MUSC) and National Cancer Institute (NCI) initiated a phase II ABC-107 trial to evaluate the efficacy of opaganib in addition to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) (103193; Pro00095537; 1P01CA203628-01; NCT04207255). The non-randomized, open-label trial intends to enroll approximately 60 patients in the US and is supported by a grant awarded by NCI to MUSC [19] [83] .
In August 2015, RedHill Biopharma reported that in early stage and advanced prostate cancer models, oral opaganib disrupted oncogenic signaling including androgen receptor pathways that are deregulated in prostrate cancer. Oral opaganib led to significant inhibition of tumour growth, proliferation, and cell cycle progression also. The study was supported by a grant from the Pennsylvania Department of Health, a Prostate Cancer Foundation Young Investigator award, and a Prostate Cancer Foundation Mazzone Challenge award [84] . National cancer Institute intends to support additional preclinical studies, which will include in vivo and in vitro models of prostate cancer in combination with radiotherapy, to determine the efficacy of opaganib. These preclinical studies will further support the clinical development of the product for the treatment of prostate cancer [10] .
Acute radiation syndrome
In February 2024, RedHill presented data from preclinical study in radiation induced lung inflammation and fibrosis in the International Journal of Molecular Sciences [85] .
As of July 2023, RedHill Biopharma in collaboration with NIAID's RNCP (The Radiation and Nuclear Countermeasures Program) is conducting preclinical studies for the treatment of gastrointestinal acute radiation syndrome (RedHill Biopharma pipeline, July 2023).
In February 2023, RedHill Biopharma announced the positive outcome of a scheduled Type B meeting with the US Food and Drug Administration (FDA) for the development of opaganib for acute radiation syndrome (ARS). The US FDA provided guidance on opaganib's developmental pathway to potential approval under the animal rule. RedHill Biopharma also reported that, sponsors of approved medical counter measures are eligible for a Priority Review Voucher (PRV) [86] .
Radiation injuries: As
of November 2022, preclinical development is underway for radiation injuries (radiation-induced hematologic and renal toxicity) in collaboration with Apogee Biotechnology Corporation . In November 2022, company released in vivo results from the trial [87] . In February 2023, company released data from the preclinical trial [86] .
SARS-COV-2 acute respiratory disease
In December 2020, RedHill Biopharma reported that in a preclinical acute respiratory distress syndrome (ARDS) animal model administration of opaganib at 250 mg/kg demonstrated a reduction in thrombosis (blood clotting) and showed reduced blood clot length, weight and total thrombus score [88] .
In August 2021, Redhill Biopharma reported that, preliminary results from preclinical trials showed that, opaganib demonstrated a reduction of IL-6 in the basal supernatants of SARS-CoV-2 infected human airway epithelial cells and reduced thrombosis in a preclinical model of ARDS [28] .
Solid tumours
RedHill Biopharma and Apogee completed a dose-escalation phase I trial of opaganib in July 2015, which met the primary endpoint, indicating that it can be safely given to patients with several types of advanced solid tumours, at dosage predicted to have therapeutic activity (NCT01488513; ABC-101). The trial was aimed to establish the dose for phase II trials which are expected to use opaganib alone and in combination with approved anticancer drugs. The trial enrolled 21 patients in the US, most with gastrointestinal cancers, including pancreatic, colorectal and cholangiocarcinoma cancers. Data from this trial will be used to support phase II and phase III trials. As of October 2013, the maximum tolerated dose had not yet been reached. The trial was conducted at the Medical University of South Carolina, and supported by grants from the NCI and the FDA's Office of Orphan Products Development [79] [89] [90] [91] [92] . Final results from the study released by the company in June 2016, showed that the study met its primary and secondary endpoints [81] . In January 2017, the company released additional positive results showing that opaganib may be an effective drug for the treatment of cholangiocarcinoma [93] . In April 2017, the company published results from the trial demonstrating that the drug is well-tolerated and can be safely administered to cancer patients; six of the 21 patients treated in the phase I study had stable disease as their best response and one patient with cholangiocarcinoma developed a partial response. The administration of the drug resulted in a rapid and pronounced decrease in S1P levels over the first 12 hours, with return to baseline at 24 hours, consistent with clearance of the drug [94] .
In November 2010, the US FDA approved an IND for the opaganib for the treatment of cancer. Preclinical data indicated that the compound may have potential in the treatment of breast, colon, lung, liver, kidney and pancreatic cancers [95] .
Other cancer
RedHill Biopharma intends to initiate two phase I/II trials for multiple oncology and inflammatory indications [96] .
As of April 2023, RedHill Biopharma in collaboration with Stanford University School of Medicine intended to initiate a phase Ib ABC-104 trial to evaluate opaganib as a radioprotectant for the prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy, however the trial is currently on hold. RedHill Biopharma intends to fund the study [77] [97] [98] [93] [9] [10] [99] [100] [101] [102] .
RedHill Biopharma, in collaboration with Apogee Biotechnology and Louisiana State University Health Sciences Center, withdrew a phase Ib/II trial due to lack of recruitment, that was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of opaganib, administered as oral gelatin capsule, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primarily in patients with HIV-related DLBCL (NCT02229981; ABC102). The study was also to determine the maximum tolerated dose of opaganib in this patient population. The trial was initiated in June 2015 and intended to enrol approximately 33 patients in the US. The trial is partly funded by the NCI Small Business Technology Transfer programme (STTR) [103] [104] [99] [105] . In June 2016, RedHill BioPharma had reported that the study was on administrative hold pending consideration of protocol amendment, which was aimed at improving recruitment prospects [81] . The company reported in January 2017, that kaposi sarcoma patients were also to be included in the study [93] .
As of April 2023, RedHill Biopharma announced that it had no further intention to pursue the development of opaganib for multiple myeloma, hence the development in multiple myeloma was discontinued [77] . In May 2019, RedHill Biopharma terminated a phase Ib/II ABC-103 trial of opaganib, due to expiration of National Cancer Institute (NCI) funding of the study, in patients with refractory or relapsed multiple myeloma who had previously received proteasome inhibitors and immunomodulatory drugs (1R44CA199767-01; Pro00062304; NCT02757326). The open-label, dose-escalation trial intended to enrol approxmately 77 patients in the US. The phase Ib portion of the trial was to evaluate safety and determine the maximum tolerated dose, while the phase II portion was to assess overall treatment response rate and overall survival. The trial had received Institutional Review Board (IRB) approval from Duke University (DUHS IRB). The NCI had awarded an SBIR grant of $US2 million to support the trial [106] [107] [108] [81] [24] [109] [89] [11] [110] .
Other indications
As of April 2023, Redhill Biopharma intended to initiate a phase II ABC-105 trial to evaluate the efficacy of opaganib in patients with moderate to severe ulcerative colitis by the proportion of patients who are in remission at the end of treatment, however, the trial is currently on hold [77] .
In 2018, Redhill Biopharma completed a phase I ABC-109 trial which was designed to evaluate the effect of food on the absorption and bioavailability of opaganib also as a solution via nasogastric (NG) tube under fed conditions. The bioavailability trial enrolled 23 healthy volunteers in the US.
In June 2022, Redhill Biopharma reported that in Normal Human Bronchial Epithelial Cells (NHBE) assay, opaganib at low concentrations demonstrated potent in vitro inhibition of influenza A H1N with no toxicity at these levels. The company was in discussions with the National Institutes of Health to decide on the steps to evaluate the antiviral potential of opaganib [111] .
As of February 2023, preclinical development of opaganib, in collaboration with the US Army and NIAID, for various antiviral indications is ongoing.
In September 2021, Redhill Biopharma released preclinical data and demonstrated that opaganib significantly decreased renal fibrosis in unilateral ureteral obstruction-induced renal interstitial fibrosis model [112] .
In preclinical studies, opaganib demonstrated both anti-inflammatory and anti-viral activities, with the potential to reduce lung inflammatory disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. Pre-clinical in vivo studies show that opaganib decreased fatality rates from influenza-virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids [48] .
In November 2016, RedHill Biopharma and Apogee Biotechnology presented results from non-clinical studies demonstrating the potential anti-tumour and anti-inflammatory effects of opaganib in combination with radiation at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium (EORTC-NCI-AACR-2016) [113] [114] .
In October 2013, Apogee Biotechnology Corporation reported that opaganib has demonstrated activity in animal models of inflammatory bowel disease, rheumatoid arthritis and radiation poisoning [91] .
Apogee Biotechnology evaluated the efficacy of opaganib in a rat model of osteoarthritis. Positive data were presented [115] .
Favourable pharmacokinetic and pharmacodynamic data for opaganib for the prevention of liver disorders were presented [116] [117] .
Apogee has synthesised two series of compounds with SK inhibitory activity, of which the lead candidates, opaganib and ABC 747080, have been shown to be orally available, well tolerated in mice and to possess excellent pharmacokinetics [118] .
Financing information
In March 2024, RedHill Biopharma announced that opaganib was selected by the Biomedical Advanced Research and Development Authority (BARDA), a component of the Administration for Strategic Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), and the CCRP is managed by the National Institute of Allergy and Infectious Diseases (NIAID), part of the HHS National Institutes of Health (NIH) for evaluation as a potential medical countermeasure (MCM) against inhalation Sulfur Mustard exposure. The effectiveness of opaganib in treating acute respiratory distress syndrome (ARDS) and sub-chronic fibrosis arising from sulphur mustard exposure will also be evaluated as part of the overall assessment [119] .
In July 2023, Redhill announced that Apogee Biotechnology Corporation, the Company's development partner, has received an additional $US1.7 million in US Government funding for opaganib through a Small Business Innovation Research (SBIR) grant. This SBIR grant will fund research to advance development of opaganib as a medical countermeasure (MCM) for gastrointestinal acute radiation syndrome (GI-ARS) [120]
In June 2022, Redhill Biopharma announced that it is seeking external funding through grants, platform studies and other public, private and industry partnerships to support development of opaganib [111] .
In January 2021, RedHill Biopharma announced its intention to raise $US10 million from a public offering. The company intends to use the funds for clinical development programs, commercialisation activities and for acquisitions and general corporate purposes [121] .
In September 2020, RedHill Biopharma's partner, Apogee Biotechnology Corporation, was awarded an $US300 000 grant from the State of Pennsylvania's COVID-19 Vaccines, Treatments and Therapies (CV-VTT) program. Opaganib was selected for the grant from this CV-VTT program, which supports the rapid advancement of promising COVID-19 therapies. This grant will cover preclinical mechanistic research to further explore opaganib's potential role in suppressing the extent and/or duration of COVID-19-related acute respiratory distress syndrome (ARDS) [122] .
In May 2016, RedHill Biopharma announced that Medical University of South Carolina was awarded with grant of $US1.8 million for a period of five years, by National Cancer Institute (NCI), to support studies on feasibility of targeting sphingolipid metabolism for treatment of variety of solid tumours. Part of the grant will also support a planned phase II trial, for hepatocellular carcinoma [79] .
RedHill Biopharma reported in June 2015 that the development of opaganib has been funded through grants and contracts in excess of $US14 million from the US federal and state government agencies, such as the FDA, Department of Defense (DoD) and the National Institutes of Health (NIH), including the National Cancer Institute and BARDA [104] [41] .
Patent Information
In September 2023, RedHill Biopharma announced that the US Patent and Trademark Office (USPTO) issued a Notice of Allowance for a new patent covering opaganib for the treatment of Ebola virus disease. The allowed patent is expected to expire no earlier than October 2035 [123] .
In May 2023, RedHill Biopharma announced that the US Patent and Trademark Office (USPTO) granted a patent for opaganib in respect to combination compositions in the treatment of cancer. The patent will be valid until October 2036 [124] .
In October 2022, The US Patent and Trademark Office (USPTO) granted a patent for a new method of use for inhibiting a coronavirus-caused disease in patients with pneumonia who are receiving supplemental oxygen at a fraction of inspired oxygen (FiO2) up to and including 60%. In May 2021, RedHill Biopharma received a Notice of Allowance from the US Patent and Trademark Office (PTO) for a new patent covering opaganib as a method for the treatment of COVID-2019 caused by the SARS-CoV-2 virus. Opaganib granted new COVID-19 treatment patent and is expected to expire in 2041 [3] [125] [42] .
In August 2021, US Patent and Trademark Office (USPTO) issued a patent for opaganib for the treatment of ebola virus infections, with patent protection until 2035 [126] .
In November 2020, RedHill Biopharma received a Notice of Allowance from the US PTO for a new patent application related to the use of opaganib (Yeliva®) and upamostat [see Adis Insight Drug profile 800021537] combination therapy for the treatment of solid tumors. The patent is expected to expire in 2036 [127] .
In September 2017, RedHill Biopharma received a Notice of Allowance from the US PTO regarding a patent to Yeliva® and Mesupron [see Adis Insight Drug profile 800021537] covering the use of proprietary investigational compounds in combination with a known antibiotic. The patent covers combination for the potential treatment of cancer, prevention of cancer recurrence or progression and inhibition of growth and proliferation of cancer cells [128] .
RedHill Biopharma submitted a trademark application, in August 2015, to the US Patent and Trademark Office for the new brand name YELIVA™ for opaganib [84] .
In March 2008, Apogee Biotechnology was issued its first patent (7 338 961) entitled "Sphingosine kinase inhibitors". This patent specifically protects the lead development compound, opaganib, and related chemotypes.
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Capsule, Pill, unspecified
- Class Adamantanes, Amides, Anti-inflammatories, Antineoplastics, Antirheumatics, Antithrombotics, Antivirals, Chlorobenzenes, Pyridines, Small molecules
- Target Sphingosine kinase
- Mechanism of Action Sphingosine kinase inhibitors
-
WHO ATC code
A07E (Intestinal Antiinflammatory Agents)
J05 (Antivirals for Systemic Use)
L01 (Antineoplastic Agents)
M01 (Antiinflammatory and Antirheumatic Products)
V03 (All Other Therapeutic Products)
-
EPhMRA code
A7E (Intestinal Anti-Inflammatory Agents)
J5 (Antivirals for Systemic Use)
L1 (Antineoplastics)
M1 (Anti-Inflammatory and Anti-Rheumatic Products)
V3 (All Other Therapeutic Products)
- Chemical name (7S)-3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide
- Molecular formula C23 H25 Cl N2 O
- SMILES C12(CC3CC(C1)(CC(C3)C2)C(NCC1=CC=NC=C1)=O)C1C=CC(=CC=1)Cl
-
Chemical Structure
- CAS Registry Number 915385-81-8
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
adenocarcinoma |
Eligibility Criteria |
Testosterone |
|
|
bladder cancer |
Arm Group Description |
sphingosine kinase 2 |
|
|
carcinoma |
Eligibility Criteria |
Testosterone |
|
|
cholangiocarcinoma |
Arm Group Description |
sphingosine kinase 2 |
|
|
cholangiocarcinoma |
Outcome Measure |
RAC-alpha serine/threonine-protein kinase (AKT) potassium calcium-activated channel subfamily N member 2 c-Myc 3'-phosphoadenosine 5'-phosphosulfate synthase 2 |
|
|
COVID 2019 infections |
Outcome Measure |
C-reactive protein (CRP) |
|
|
COVID-19 pneumonia |
Brief Title |
sphingosine kinase 2 |
|
|
COVID-19 pneumonia |
Official Title |
sphingosine kinase 2 |
|
|
diffuse large B cell lymphoma |
Outcome Measure |
T-cell surface antigen CD4 Sphingosine 1-phosphate |
|
|
ductal carcinoma |
Eligibility Criteria |
Testosterone |
|
|
Kaposi's sarcoma |
Outcome Measure |
T-cell surface antigen CD4 Sphingosine 1-phosphate |
|
|
liver cancer |
Arm Group Description |
sphingosine kinase 2 |
|
|
liver cancer |
Outcome Measure |
globotriaosyl lysosphingolipid c-Myc |
|
|
multiple myeloma |
Brief Summary |
Syndecan-1 (SDC1 sphingosine phosphorylcholine sphingosine kinase 2 Sphingosine potassium calcium-activated channel subfamily N member 2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 |
|
|
multiple myeloma |
Detailed Description |
Syndecan-1 (SDC1 Sphingosine 1-phosphate RPS6 potassium calcium-activated channel subfamily N member 2 MCL1 Interleukin-6 (IL-6) c-Myc 3'-phosphoadenosine 5'-phosphosulfate synthase 2 |
|
|
multiple myeloma |
Eligibility Criteria |
PSA |
|
|
ovarian cancer |
Arm Group Description |
sphingosine kinase 2 |
|
|
pancreatic cancer |
Arm Group Description |
sphingosine kinase 2 |
|
|
prostate cancer |
Eligibility Criteria |
Testosterone |
|
|
solid tumours |
Arm Group Description |
sphingosine kinase 2 |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Opaganib - RedHill Biopharma | 3'-phosphoadenosine 5'-phosphosulfate synthase 2 | Brief Summary, Detailed Description, Outcome Measure |
| c-Myc | Detailed Description, Outcome Measure | |
| C-reactive protein (CRP) | Outcome Measure | |
| globotriaosyl lysosphingolipid | Outcome Measure | |
| Interleukin-6 (IL-6) | Detailed Description | |
| MCL1 | Detailed Description | |
| potassium calcium-activated channel subfamily N member 2 | Brief Summary, Detailed Description, Outcome Measure | |
| PSA | Eligibility Criteria | |
| RAC-alpha serine/threonine-protein kinase (AKT) | Outcome Measure | |
| RPS6 | Detailed Description | |
| Sphingosine | Brief Summary | |
| Sphingosine 1-phosphate | Detailed Description, Outcome Measure | |
| sphingosine kinase 2 | Arm Group Description, Brief Summary, Brief Title, Official Title | |
| sphingosine phosphorylcholine | Brief Summary | |
| Syndecan-1 (SDC1 | Brief Summary, Detailed Description | |
| T-cell surface antigen CD4 | Outcome Measure | |
| Testosterone | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Acute radiation syndrome | Gastrointestinal acute radiation syndrome | - | Preclinical | USA | PO / unspecified | RedHill Biopharma | 01 Oct 2013 |
| COVID 2019 infections | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 28 Jun 2021 |
| COVID 2019 infections | - | - | Preclinical | USA | PO / unspecified | University of Louisville | 28 Jun 2021 |
| COVID-19 pneumonia | - | Adjunctive treatment | Phase II/III | Colombia, United Kingdom | PO / unspecified | RedHill Biopharma | 29 Jan 2021 |
| COVID-19 pneumonia | - | Adjunctive treatment | Phase II/III | Brazil, Israel, Italy, Mexico, Peru, Poland, Russia, USA | PO / Capsule | RedHill Biopharma | 07 Oct 2020 |
| COVID-19 pneumonia | compassionate use program; addition to standard-of-care, including hydroxychloroquine background therapy | Combination therapy | Clinical Phase Unknown | Israel | PO / unspecified | RedHill Biopharma | 06 Apr 2020 |
| COVID-19 pneumonia | Compassionate Use Programme | - | Clinical Phase Unknown | Switzerland | PO / unspecified | RedHill Biopharma | 22 Mar 2021 |
| Cancer | - | Combination therapy | No development reported (Clinical) | USA | PO / Capsule | RedHill Biopharma | 28 Oct 2020 |
| Cholangiocarcinoma | - | Inoperable/Unresectable, Late-stage disease, Monotherapy, Second-line therapy or greater | Phase II | USA | PO / unspecified | RedHill Biopharma | 22 Dec 2017 |
| Cholangiocarcinoma | in combination with hydroxychloroquine sulphate | Combination therapy, Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater | Phase II | USA | PO / unspecified | RedHill Biopharma | 13 Mar 2020 |
| Ebola virus infections | - | - | Preclinical | USA | PO / unspecified | RedHill Biopharma | 03 Oct 2023 |
| Inflammatory bowel diseases | - | - | No development reported (Preclinical) | USA | PO / unspecified | Apogee Biotechnology Corporation | 04 Nov 2017 |
| Influenza A virus infections | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 23 Jun 2022 |
| Liver cancer | - | Late-stage disease, Second-line therapy or greater | Suspended (II) | USA | PO / unspecified | Apogee Biotechnology Corporation, RedHill Biopharma, Medical University of South Carolina | 12 Sep 2019 |
| Multiple myeloma | - | Second-line therapy or greater | Discontinued (I/II) | USA | PO / unspecified | RedHill Biopharma | 28 Apr 2023 |
| Osteoarthritis | - | - | No development reported (Preclinical) | USA | PO / unspecified | Apogee Biotechnology Corporation | 04 Nov 2017 |
| Prostate cancer | in combination with abiraterone and enzalutamide | Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater | Phase II | USA | PO / unspecified | Medical University of South Carolina | 18 Mar 2020 |
| Radiation injuries | Nuclear Radiation Injury | - | Preclinical | Israel | PO / Pill | RedHill Biopharma | 17 Nov 2022 |
| Renal fibrosis | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 07 Sep 2021 |
| Rheumatoid arthritis | - | - | No development reported (Preclinical) | USA | PO / unspecified | Apogee Biotechnology Corporation | 04 Nov 2017 |
| SARS-CoV-2 acute respiratory disease | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 15 Dec 2020 |
| Solid tumours | - | Late-stage disease | No development reported (I) | USA | PO / Capsule | Apogee Biotechnology Corporation | 28 Dec 2019 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Cholangiocarcinoma | - | USA | RedHill Biopharma | 04 Apr 2017 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Apogee Biotechnology Corporation | Originator | USA |
| RedHill Biopharma | Owner | Israel |
| Kukbo | Licensee | South Korea |
| National Institutes of Health (USA) | Funder | USA |
| Biomedical Advanced Research and Development Authority | Funder | USA |
| Prostate Cancer Foundation | Funder | USA |
| Food and Drug Administration | Funder | USA |
| National Cancer Institute (USA) | Funder | USA |
| Medical University of South Carolina | Collaborator | USA |
| Louisiana State University Health Sciences Center | Collaborator | USA |
| Mayo Clinic | Collaborator | USA |
| Duke University | Collaborator | USA |
| University of Louisville | Collaborator | USA |
| University of Utah | Collaborator | USA |
| M. D. Anderson Cancer Center | Collaborator | Usa |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
| Stanford University School of Medicine | Collaborator | USA |
Licensing Availability
| Licensing Organisation | Available Indication | Available Phase | Region | Date |
|---|---|---|---|---|
| RedHill Biopharma | Cancer, Inflammation | Unspecified | - | 21 Nov 2016 |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| YELIVA | RedHill Biopharma | Unspecified | USA |
Scientific Summary
Pharmacokinetics
The half-time for clearance of opaganib from plasma was determined to be approximately 4 hours in a phase I clinical trial in patients with advanced solid tumours. In addition, through at least the first 3 cohorts, the pharmacokinetics of opaganib were shown to be proportional to the dose of opaganib that was administered. The average Cmax for patients receiving 500 mg was 16.4µm, which was sufficient for anti-cancer efficacy in preclinical models. Patients either received 250 mg four times daily (6 patients), 250 mg twice-daily (4 patients), 500 mg twice-daily (4 patients) or 750 mg twice-daily (3 patients) in the open-label study [91] .
In both combination treatments decreases in ERK phosphorylation and an increase in the phosphorylation of inhibitory site of c-Raf (S259) were observed in both sets of cancer cells. The study evaluated opaganib (a SK2-specific inhibitor) and ABC 294735 (a SK1/SK2 inhibitor), alone and in combination with sorafenib on human pancreatic adenocarcinoma (Bxpc-3) and kidney carcinoma (A- 498) cells in vitro and in vivo [130]
Oral opaganib had dose-proportional peak plasma levels and a t½ value of approximately 8h in rats. At a dose of 50 mg/kg, it had plasma Cmax values of approximately 100, 30 and 15 µmol/L for the parent compound, and its two main metabolites M1 and M2, respectively. Significant levels of opaganib were detected in the liver, kidney, and brain of normal rats, and these were correlated with plasma pharmacokinetics indicating effective biodistribution of the compound. opaganib accumulated at therapeutically effective concentrations in the tumours of mice bearing xenograft of JC mammary adenocarcinoma cells (>50 µg/g or ≅125 µmol/L), and promoted progressive apoptosis in the tumours for at least 5 days [117] .
Adverse Events
In updated data from a phase II trial in patients (n=40) with COVID-19 pneumonia, opaganib was safe and well tolerated, with adverse events balanced between treatment arms. There were two intubations and three deaths in each group. There were three patients with serious adverse events (SAEs) in the opaganib group vs. five in the placebo group. No SAEs were considered related to study drug. Previously, in the preliminary data in patients (n=40) with COVID-19 pneumonia opaganib was safe, with no material safety differences between opaganib and control arms. In tolerability profile, diarrhoea was the main treatment emergent difference [55] [56] [58] [62] .
In a phase Ib/II trial, administration of opaganib did not show dose-limiting toxicities, in 10 evaluable patients belonging to the phase Ib portion [106] .
Results from a phase I trial in patients with advanced solid tumours showed that treatment with opaganib was safe and well tolerated, with grade 1-2 fatigue and nausea being the most common adverse events. Several patients experienced mild neuropsychiatric symptoms, such as anxiety and mood changes, which were resolved quickly upon discontinuation of study medication. All treatment-related adverse events were rapidly reversible upon dose reduction or study drug removal. The results also showed that opaganib could be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity. opaganib caused only a modest decrease in lymphocyte count compared with other S1P receptor-targeting agents such as fingolimod [see Adis Insight drug profile 800006154] and ozanimod [see Adis Insight drug profile 800033563]. The phase I trial enrolled 21 patients with advanced solid tumours [81] [91] [89] [92] .
In the first five patients with severe COVID-19 infections (compassionate use), the treatment with opaganib was found to be safe and well tolerated. An improvement in clinical and laboratory parameters was demonstrated for opaganib-treated patients compared to matched case-controls [69] . Adverse events data obtained from a clinical trial in Israel in two of the COVID-19 patients indicated that at doses administered, opaginib was found to be well tolerated with no treatment emergent adverse events [66] [68] .
Results from phase II/III trial in patients with COVID-19 pneumonia demonstrated that the opaganib is safe and well tolerated. Overall adverse events were balanced between the opaganib and placebo groups, suggesting good safety, with no new safety signals emerging, further supporting potential use in this patient population and earlier stage populations [52] [53] [31] [30]
Pharmacodynamics
Summary
Phase I
Results from a phase I trial that evaluated 21 patients with advanced solid tumours showed that dosing with opaganib rapidly decreased S1P plasma levels over the first 12 hours, with a return to baseline by 24 hours, consistently with drug clearance [81] [89] [92] .
Preclinical studies
ABC treatment arrested elevations of TNF and S1P and reduced histological damage in the small intestines of non-tumour bearing irradiated mice, and significantly increased long-term survival. In tumour models, total body irradiation (1 Gy) caused moderate inhibition of tumour growth in the syngeneic PAN02 and B16 tumour models, but did not show activity against the E0771 tumours. ABC alone demonstrated strong, moderate and no anti-tumor activity in the PAN02, B16 and E0771 models, respectively. Combination of ABC with radiation exerted significant anti-tumour activity in all three models. Use of higher radiation doses (3 Gy) and addition of cisplatin in partially shielded nude mouse models resulted in strong suppression of the growth of both human tumor xenografts (22Rv1 and FaDu). The addition of ABC in the 22Rv1 model did not alter the response to radiation/cisplatin; whereas, this combination showed increased suppression of tumour growth in the FaDu model. C57BL/6 mice were subjected to either total body or partially-shielded irradiation and were treated with ABC alone; radiation alone; or combination of ABC plus radiation. Cisplatin was combined with radiation with or without ABC in the 22Rv1 and FaDu. Syngeneic tumor models comprised C57BL/6 mice implanted with PAN02 (pancreatic), B16 (melanoma) or E0771 (breast) cancer cells; while cross-species xenograft models used NCr nude mice implanted with human 22Rv1 (prostate) or human FaDu (pharynx squamous cell carcinoma) cancer cells [113] .
In vivo testing revealed ABC 29464 plus sorafenib or ABC 294735 plus sorafenib resulted in synergistic cytotoxicity, which was associated with increases in caspases 3/7 activation and apoptotic DNA fragmentation in mice with either Bxpc-3 or A-498 cancer cells. In both combination treatments decreases in ERK phosphorylation and an increase in the phosphorylation of inhibitory site of c-Raf (S259) were observed in both sets of cancer cells. Both opaganib and ABC 294735 delayed tumour growth in both xenograft models without overt toxicity to the animals. Sorafenib co-administration potentiated this growth delay. The study evaluated opaganib (a SK2-specific inhibitor) and ABC 294735 (a SK1/SK2 inhibitor), alone and in combination with sorafenib on human pancreatic adenocarcinoma (Bxpc-3) and kidney carcinoma (A- 498) cells in vitro and in vivo [130] .
Apogee has identified several low molecular weight compounds that potently inhibit sphingosine kinase in close relationship with their anti-proliferative activities [132] .
In preclinical studies, administration of opaganib resulted in a comprehensive inhibition of myeloma tumour growth in vitro and in vivo, in mouse xenograft models. Results have also revealed that sphingosine kinase 2 (SK2) is over-expressed in multiple myeloma cell lines and human multiple myeloma specimens and is critically involved in myeloma cell growth, proliferation and survival [106] .
In preclinical study, administration of upamostat and opaganib demonstrated tumour regression in mice model of cholangiocarcinoma. Body weights of the mice reported no differences in inter- or intra- group. The combination of upamostat and opaganib reported greater regression compared to either upamostat or opaganib alone. Change in tumour volumes at Day 42 was reported to be 102.0, 93.31, 86.09 for opaganib, upamostat and combination respectively with p values 0.0002, 0.0010 and 0.0008 [23] .
In vivo
results from a preclinical trial evaluating the effects of opaganib on radiation-induced hematologic and renal toxicity demonstrated that opaganib showed a protective impact on key hematological and kidney function parameters following total body irradiation (TBI) [87]
In preclinical studies WX UK1 and opaganib increased mRNA and protein expression of specific serine proteases, sphingosine kinases and sphingosine receptors. Cell migration was significantly inhibited in treated versus non-treated cells. Both opaganib and the combination of WX UK1 with opaganib substantially inhibited migration of both cell lines in vitro . Both drugs also decreased cell via-bility in the migration assays. Upamostat and opaganib in combination have significant inhibitory effects on both Cholangiocarcinoma (CCA) cell migration and viability in vitro which may prevent tumor progression [22] .
Results from the preclinical in vivo studies demonstrated the potential of opaganib in nuclear radiation protection. Opaganib showed association with protection of normal tissue, including gastrointestinal tissue, from radiation damage due to ionizing radiation exposure or cancer radiotherapy [86] .
In preclinical studies, in Ebola virus in vitro study demonstrated robust synergistic effect when combined individually with remdesivir significantly improving viral inhibition while maintaining cell viability. These encouraging in vitro results for opaganib and RHB 107 showed a distinct synergy in terms of viral inhibition while maintaining cell viability (i.e. not increasing toxicity), when either is added to remdesivir, with opaganib showing the greatest synergistic effect in combination with remdesivir,demonstrated robust synergistic effect when combined individually with remdesivir significantly improving viral inhibition while maintaining cell viability [76]
Data from the preclinical study in radiation induced lung inflammation and fibrosis showed that radiation-induced lung inflammation and fibrosis in an in vivo mouse model of lung damage following exposure to ionizing radiation was reduced by Opaganib. The opaganib group treated both during the initial and delayed phases of inflammation demonstrated a highly statistically significant improvement in survival at Day 180 (60% survival compared with 10% for controls, p=0.008). Treatment with opaganib during both initial and delayed phases of inflammation provided the greatest improvement in survival [85] .
Following hepatic ischaemia-repefusion (IR), the 7-day survival increased from 28% to 100% in mice treated with opaganib, compared with vehicle treated mice. Additionaly, the changes seen in vehicle-treated mice, 6h after hepatic IR, including increases in ALT, bilirubin, hepatic necrotic cell death, TUNEL-positive apoptotic cells and cleaved caspase-3, were attenuated by 54% to 91% in mice treated with opaganib. Hepatic IR also resulted in mitochondrial depolarisation in 74% of viable hepatocytes, compared with 17% of hepatocytes in opaganib-treated mice [116] .
Treatment with oral opaganib (50 mg/kg bid) for 27 days prevented incapacitance (measured as hind limb weight bearing) in a rat model of osteoarthritis. As weight bearing (%) significantly decreased from 48.8 (day 0) to 41.9 (day 28) following sham oral dosing, these values did not change on day 0 (49.0%) and day 28 (48.8%) in rats receiving opaganib or tramadol treatment. Knee joint histology scores (48 point scale) indicating cartilage and bone destruction were reduced to 24.1 in rats receiving opaganib compared with 30.9 in sham group. There was a significant inverse correlation between histological damage and weight bearing in rats (p=0.036). Moreover, proteoglycan staining in the tibia and femur showed lesser disruption in rats treated with opaganib compared with sham group [115] .
Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, inhibiting viral replication of all SARS-CoV-2 variants tested to date in an in vitro model of human lung bronchial tissue. Additionally, preclinical in vivo studies have demonstrated opaganib's potential to ameliorate inflammatory lung disorders, such as pneumonia, have demonstrated opaganib's potential to decrease renal fibrosis and have shown decreased fatality rates from influenza virus infection and amelioration of pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids. Opaganib also demonstrated reduced blood clot length, weight and total thrombus score in a preclinical model of acquired respiratory distress syndrome [52] [5] [31] .
The Preclinical data showed that opaganib is potent in vitro efficacy against the Omicron SARS-CoV-2 variant, while maintaining host cell viability. Based on the new and previously announced data, opaganib's unique human host-targeted, dual antiviral and anti-inflammatory suggested mechanism is expected to act independently of viral spike protein mutations and remain effective against Omicron sub-variants BA.2, XE and other emerging and future variants. Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, inhibiting viral replication of the original SARS-CoV-2 and variants tested to date in an in vitro model of human lung bronchial tissue [26] .
Result from invitro studies using a primary human nasal epithelial cell culture model of Omicron BA.5 demonstrated that RHB 107 and opaganib inhibited Omicron sub-variant BA.5 viral replication which is indicative of antiviral activity [74]
In in vitro studies opaganib demonstrated potent inhibition of influenza A H1N1, at low concentrations and with no evidence of toxicity at these levels in a Normal Human Bronchial Epithelial Cells (NHBE) assay, the natural human target of the virus, making it a realistic model. Opaganib inhibited multiple pathways, induce autophagy and apoptosis, and disrupt the viral RTC (replication-transcription complex) through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SK2, DES1 and GCS) [3] .
Results from an in vivo study in Ebola virus infection model showed a statistically significant survival increase in mean (SE) survival time of 11.2 (2.6) days in the 150 mg/kg opaganib group (p=0.0279) compared with a mean (SE) survival time of 5.5 (0.4) days in the inactive vehicle control group. A 30% mice survival was observed in the 150 mg/kg treated group compared to the vehicle control [75] .
Antimicrobial Activity
Summary
Therapeutic Trials
In a phase Ib/II trial, administration of opaganib showed that out of 10 evaluable patients, two had stable disease for over four months, while one achieved a very good partial response (VGPR). These patients belonged to the phase Ib portion of the trial [106] .
Results from 16 patients, with solid tumours from a phase I trial, assessable for response by RECIST 1.1 criteria showed that, one patient had a partial response with a progression-free survival of 16.9 months, and six patients, including one with metastatic/recurrent bladder cancer, had stable disease with a progression-free survival of between 3.5 and 17.6 months. Of the three patients with cholangiocarcinoma, one had a partial response and the other two had stable disease, one for over a year. In this phase I trial, 21 patients with advanced solid tumours were continuously treated in cycles of 28 days with opaganib, in the absence of disease progression, and tumours were reimaged every two cycles [81] [91] . Additional results from the phase I trial in three cholangiocarcinoma patients showed that one patient had a sustained partial response (Overall Survival (OS) = 20.3 months) and the other two had stable disease (OS = 17.6 and 16.3 months) [93] [92] .
Updated data from the phase II study showed that 50% vs 22% of patients treated with opaganib (n=22) reached room air by Day 14 compared with placebo group (n=18). The benefit was maintained regardless of receiving dexamethasone and/or remdesivir. At day 14, 86.4% of patients treated with opaganib were discharged compared with 55.6% of placebo. Median discharge time was six and 7.5 days for opaganib and placebo group respectively. Two-point improvement in the WHO Ordinal Scale was observed in 81.8% opaganib patients compared with 55.6% of patients in the placebo group. This improvement was achieved in a median time of 6 days versus 7.5 days, respectively. Earlier top-line results from a phase II study showed that administration of opaganib resulted in improvement in reducing overall oxygen requirement in patients (n=40) with COVID-19 pneumonia. By the end of the treatment on day 14, greater improvement in the proportion of patients requiring oxygen support was reported, i.e. 52.6% vs. 22.2% in control arm. The patients reported with 50% reduction in supplemental oxygen in opaganib vs. the control arm was 89.5% vs. 66.7% by day 14 and 68% vs. 44% by day seven. Rate of discharge of patients was reported 73.7% compared to 55.6% in control arm. A greater reduction from baseline of the median total oxygen requirement (AUC) was also reported over 14 days vs. the control arm (68.0% vs. 46.7%). These benefits were maintained regardless of concurrent standard of care. Key primary and secondary efficacy outcomes, correlating with clinical improvement were measured as defined by the WHO ordinal scale [56] [58] [62] .
Results from the first five patients with severe COVID-19 infections showed substantial benefit to patients treated with opaganib under compassionate use in both clinical outcomes and inflammatory markers as compared with a retrospective matched case-control group (n=18) from the same hospital. All patients in the opaganib-treated group were discharged from hospital on room air, without having required intubation and mechanical ventilation, whereas 33% of patients in the control group required intubation and mechanical ventilation. The median time to weaning from high-flow nasal cannula was reduced to 10 days in the opaganib-treated group, as compared to 15 days in the control group. Improvement in lymphocyte counts was faster in opaganib-treated patients as compared with patients in the control group. The C-reactive protein showed faster improvement in the opaganib treated group as compared to the control group [69] [70] . Updated efficacy data obtained from a clinical trial in Israel in six of the COVID-19 patients showed significant improvements following treatment with opaganib with and without hydroxychloroquine including decreased supplemental oxygen requirements, decreased C-reactive protein levels and increased lymphocyte levels. Five of the six patients analysed were weaned from oxygen, and three patients were discharged from the hospital within days of treatment initiation [64] [66] [68] .
Phase II/III
: In a phase II/III trial, treatment with opaganib showed positive efficacy results in non-hospitalized patients with COVID-19 infections demonstrating 100% reduction in hospitalizations due to COVID-19 and an 87.8% reduction in reported new severe COVID-19 symptoms [54] . Previous updated results from the trial in hospitalized patients with severe COVID-19 pneumonia demonstrated that the opaganib treatment resulted in a statistically significant 62% reduction in mortality (7/117 patients treated with opaganib vs. 21/134 for placebo; nominal p-value=0.019, Relative Risk 2.6) (Sensitivity Analysis: 5/117 vs. 16/134, 64% efficacy benefit; nominal p-value=0.033, Relative Risk - 2.8). 77% of opaganib-treated patients reached room air by day 14 vs. 63.5% for placebo – an efficacy benefit of 21% with opaganib (nominal p-value= 0.033). Patients treated with opaganib showed median time of 10 days to discharge vs. 14 days for the placebo arm, resulting in a saving of four days hospitalization per opaganib patient and saving a total of 524 cumulative days of hospitalization across the group by day 42, nominal p-value=0.0195. The moderately severe group comprised 53% of study participants requiring a Fraction of inspired Oxygen (FiO2) up to 60% at baseline (inhaled supplemental oxygen via nasal cannula or face mask). The data also supported opaganib's potential use in earlier stages of COVID-19 disease, consistent with opaganib's US phase II study results and the demonstrated potent antiviral inhibition of SARS-CoV-2 variants [52] [53] [31] .
Results from the phase II/III trial in severely ill hospitalized COVID-19 patients demonstrated that opaganib improved the median time to viral RNA clearance by at least 4 days. Treatment with opaganib resulted in viral RNA clearance in a median of 10 days while the median for clearance in the placebo arm was not reached by the end of 14-days treatment for placebo (Hazard Ratio 1.34; nominal p-value=0.043, N=437/463) [129] [31] . Additional prespecified analyses in key subpopulations from the phase II/III study also demonstrated a 70% reduction in mortality and a 34% benefit in time to recovery for patients treated with opaganib [26] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Mar 2021 | Regulatory Status | RedHill Biopharma plans to submit an application for global Emergency Use Authorisation for COVID-19 pneumonia in the first quarter of 2021 [20] | 17 Dec 2020 |
| 31 Aug 2020 | Trial Update | RedHill Biopharma plans a phase I/II trial for COVID-19 pneumonia in Israel in August 2020 (NCT04502069) (700325539) | 25 Oct 2020 |
| 31 Jul 2020 | Trial Update | RedHill Biopharma plans a phase II/III trial for COVID-19 pneumonia (Adjunctive treatment) in Russia, Mexico, Italy, Brazil, USA, United kingdom and additional EU countries (PO, Capsule) (NCT04467840) (700322943) [46] | 25 Oct 2020 |
| 01 Feb 2020 | Trial Update | Medical University of South Carolina in collaboration with National Cancer Institute (NCI) plans a phase II trial for Prostate cancer (Combination therapy, Metastatic disease, Hormone refractory) in February 2020 (NCT04207255) (700313102) | 18 Mar 2020 |
| 31 Dec 2017 | Trial Update | RedHill Biopharma plans a phase IIa trial for Cholangicarcinoman fourth quarter of 2017 [97] | 27 Dec 2017 |
| 31 Dec 2017 | Trial Update | RedHill plans a phase II ABC-105 trial for Ulcerative colitis in fourth quarter of 2017 [97] | 22 May 2023 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 20 Feb 2024 | Scientific Update | Pharmacodynamic data from the preclinical study in acute radiation syndrome released by RedHill Biopharma [85] Updated 23 Feb 2024 |
| 20 Dec 2023 | Scientific Update | Pharmacodynamics data from a preclinical study in Ebola virus infections released by RedHill Biopharma [76] Updated 27 Dec 2023 |
| 03 Oct 2023 | Phase Change - Preclinical | Preclinical trials in Ebola virus infections in USA prior to October 2023 (PO) [75] Updated 05 Oct 2023 |
| 03 Oct 2023 | Scientific Update | Pharmacodynamics data from a preclinical study in Ebola virus infections released by RedHill Biopharma [75] Updated 05 Oct 2023 |
| 05 Sep 2023 | Patent Information | RedHill Biopharma receives Notice of Patent Allowance for Opaganib for treatment of Ebola virus infections in USA [123] Updated 07 Sep 2023 |
| 21 Jul 2023 | Company Involvement | Apogee Biotechnology Corporation receives SBIR grant for opaganib development in Acute radiation syndrome [120] Updated 28 Jul 2023 |
| 20 Jul 2023 | Active Status Review | Preclinical development is ongoing for Acute radiation syndrome in USA (RedHill Biopharma pipeline, July 2023) Updated 21 Jul 2023 |
| 01 May 2023 | Patent Information | RedHill Biopharma has patent protection for opaganib in USA [124] Updated 04 May 2023 |
| 28 Apr 2023 | Phase Change - Discontinued(I/II) | Discontinued - Phase-I/II for Multiple myeloma (Second-line therapy or greater) in USA (PO) prior to April 2023 [77] Updated 22 May 2023 |
| 28 Apr 2023 | Regulatory Status | RedHill Biopharma anticipates Priority Review from US FDA Updated 04 May 2023 |
| 28 Feb 2023 | Licensing Status | RedHill Biopharma and the National Institute of Allergy and Infectious Diseases enters into a R&D agreement for Opaganib [2] Updated 06 Mar 2023 |
| 15 Feb 2023 | Regulatory Status | RedHill Biopharma receives the positive outcome of a scheduled Type B meeting from the US FDA for opaganib for Acute radiation syndrome (ARS) [86] Updated 19 Feb 2023 |
| 15 Feb 2023 | Scientific Update | Pharmacodynamics data from in vivo studies in Radiation injuries released by RedHill Biopharma [86] Updated 19 Feb 2023 |
| 17 Nov 2022 | Phase Change - Preclinical | Preclinical trials in Radiation injuries in Israel (PO), prior to November 2022 [87] Updated 22 Nov 2022 |
| 17 Nov 2022 | Regulatory Status | RedHill Biopharma plans to submit IND application for Radiation injuries [87] Updated 22 Nov 2022 |
| 17 Nov 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in Radiation injuries released by RedHill Biopharma [87] Updated 22 Nov 2022 |
| 07 Nov 2022 | Scientific Update | Pharmacodynamics data from in vitro studies in Influenza A virus infections released by RedHill Biopharma [3] Updated 13 Nov 2022 |
| 04 Nov 2022 | Scientific Update | Pharmacodynamics data from preclinical trial in Cholangiocarcinoma presented at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases [22] Updated 04 Jan 2023 |
| 19 Oct 2022 | Patent Information | RedHill Biopharma has patent protection for opaganib in US for New COVID-19 Treatment (9371255; 9373286) Updated 26 Oct 2022 |
| 03 Oct 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-19 infection released by RedHill [74] Updated 10 Oct 2022 |
| 18 Jul 2022 | Active Status Review | 9362613: QC feedback incorporated Updated 18 Jul 2022 |
| 12 Jul 2022 | Scientific Update | Efficacy data from a phase II/III trial in Covid-19 pneumonia released by RedHill Biopharma [54] Updated 12 Jul 2022 |
| 23 Jun 2022 | Phase Change - Preclinical | Preclinical trials in Influenza A virus infections in Israel (PO) [111] Updated 04 Jul 2022 |
| 21 Jun 2022 | Trial Update | RedHill Biopharma, Mayo Clinic, University of Utah and The University of Texas MD Anderson Cancer Center complete a phase IIa trial in Cholangiocarcinoma (Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater, Monotherapy, Combination therapy) in USA (PO) (NCT03377179) Updated 18 Jul 2022 |
| 12 Apr 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-2019 pneumonia released by RedHill Biopharma [26] Updated 18 Apr 2022 |
| 16 Mar 2022 | Licensing Status | Kukbo in-licenses opaganib from RedHill Biopharma [4] Updated 22 Mar 2022 |
| 13 Jan 2022 | Scientific Update | Prespecified analysis data from a phase II/III trial in COVID-19 pneumonia released by RedHill Biopharma [129] Updated 03 Feb 2022 |
| 06 Dec 2021 | Regulatory Status | Redhill Biopharma plans for submission in COVID-2019 infections in South Africa, Russia, Israel, Switzerland, India, Brazil and Colombia [27] Updated 10 Dec 2021 |
| 06 Dec 2021 | Trial Update | Redhill Biopharma plans a clinical trial in COVID-2019 infections (Omicron and other variants) [27] Updated 10 Dec 2021 |
| 04 Oct 2021 | Scientific Update | Efficacy and adverse events data from a phase II/III trial in COVID-19 pneumonia (Adjunctive treatment) released by RedHill Biopharma ) (PO) [52] [53] Updated 06 Oct 2021 |
| 15 Sep 2021 | Scientific Update | Efficacy and adverse events data from a phase II/III trial in COVID-19 pneumonia released by RedHill Biopharma [30] Updated 20 Sep 2021 |
| 07 Sep 2021 | Phase Change - Preclinical | Preclinical trials in Renal fibrosis in Israel (PO) [112] Updated 13 Sep 2021 |
| 26 Aug 2021 | Regulatory Status | RedHill Biopharma plans to seek approval for COVID-2019 infections and COVID-2019 pneumonia in USA, Europe and other countries [28] Updated 27 Aug 2021 |
| 24 Aug 2021 | Patent Information | RedHill Biopharma has patent protection for opaganib in US for treating Ebola virus infections [126] Updated 24 Aug 2021 |
| 30 Jul 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 18 Jul 2021 | Trial Update | RedHill Biopharma completes phase II/III trial in COVID-19 pneumonia (Adjunctive treatment) in Brazil, Colombia, Israel, Italy, Mexico, Poland, Peru, Russia, UK and USA (NCT04467840) [43] Updated 20 Jul 2021 |
| 28 Jun 2021 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in Israel (PO) before June 2021 [72] Updated 05 Jul 2021 |
| 28 Jun 2021 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in USA (PO) before June 2021 [72] Updated 05 Jul 2021 |
| 21 Jun 2021 | Scientific Update | Updated efficacy and adverse events data from a phase II trial in COVID-2019 infections released by RedHill Biopharma [56] Updated 25 Jun 2021 |
| 20 Jun 2021 | Scientific Update | Adverse events data from a phase II trial in COVID-2019 infections presented at World Microbe Forum 2021 (ASM-FEMS-WMF-2021) [55] Updated 13 Aug 2021 |
| 08 Jun 2021 | Trial Update | RedHill Biopharma completes enrolment in its phase II/III trial for COVID-19 pneumonia (Adjunctive treatment) in Brazil, Colombia, Israel, Italy, Mexico, Peru, Poland, Russia, United Kingdom, USA (PO, Capsule) (NCT04467840) Updated 11 Jun 2021 |
| 27 May 2021 | Regulatory Status | Redhill Biopharma plans to submit NDA to the US FDA and EMA for COVID-19 pneumonia [18] Updated 02 Jun 2021 |
| 26 May 2021 | Patent Information | RedHill Biopharma receives patent allowance for opaganib in USA [42] Updated 31 May 2021 |
| 22 Mar 2021 | Phase Change - Clinical | Clinical trials in COVID-19 pneumonia in Switzerland (PO) before March 2021 [29] Updated 26 Mar 2021 |
| 29 Jan 2021 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia (Adjunctive treatment) in Colombia (PO) (NCT04467840) [34] Updated 02 Feb 2021 |
| 28 Jan 2021 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-2019 pneumonia released by RedHill Biopharma [5] Updated 01 Feb 2021 |
| 31 Dec 2020 | Scientific Update | Top-line efficacy and safety data from a phase II trial in COVID-19 pneumonia released by RedHill Biopharma [58] Updated 04 Jan 2021 |
| 23 Dec 2020 | Trial Update | RedHill Biopharma completes a phase IIa trial in COVID-19 pneumonia in USA and Israel (PO) (NCT04414618) Updated 15 Mar 2021 |
| 15 Dec 2020 | Phase Change - Preclinical | Preclinical trials in SARS-COV-2 acute respiratory disease in Israel (PO) [88] Updated 02 Feb 2021 |
| 17 Nov 2020 | Trial Update | RedHill Biopharma completes enrolment in its phase IIa trial in COVID-19 pneumonia in USA, Israel (PO) (NCT04414618) Updated 19 Nov 2020 |
| 12 Nov 2020 | Regulatory Status | RedHill Biopharma plans to submit an application for global Emergency Use Authorisation for COVID-19 pneumonia in the first quarter of 2021 [20] Updated 17 Dec 2020 |
| 04 Nov 2020 | Patent Information | Redhill Biopharma receives patent allowance for opaganib in the US [127] Updated 09 Nov 2020 |
| 28 Oct 2020 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in Cancer(Combination therapy) in USA (PO, Capsule) Updated 28 Oct 2020 |
| 07 Oct 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia in Israel (PO) [70] (NCT04467840) Updated 12 Oct 2020 |
| 07 Oct 2020 | Regulatory Status | A CTA for a phase II/III trial in COVID-19 pneumonia approved in Israel, before October 2020 [70] (NCT04467840) Updated 12 Oct 2020 |
| 22 Sep 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumoniain Brazil (PO) [44] (NCT04467840) Updated 24 Sep 2020 |
| 22 Sep 2020 | Regulatory Status | Brazilian Health Regulatory Agency (ANVISA) approves CTA application for phase II/III trial in COVID-19 pneumonia [44] Updated 24 Sep 2020 |
| 27 Aug 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia (Adjunctive treatment) in Italy (PO) [41] (NCT04467840) Updated 31 Aug 2020 |
| 27 Aug 2020 | Regulatory Status | Italian Medicines Agency (AIFA) approves a CTA application for phase II/III trial for COVID-19 pneumonia [41] Updated 31 Aug 2020 |
| 27 Aug 2020 | Regulatory Status | RedHill Biopharma receives positive recommendation from Safety Monitoring Committee for phase II trial in US for COVID-19 pneumonia [41] Updated 31 Aug 2020 |
| 21 Aug 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia (Adjunctive treatment) in USA, Peru (PO) (NCT04467840) Updated 11 Jun 2021 |
| 21 Aug 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia (Adjunctive treatment) in Poland (PO) (NCT04467840) Updated 13 Apr 2021 |
| 11 Aug 2020 | Trial Update | Redhill Biopharma withdraws the phase I/II Opaganib-RHB trial prior to enrolment due replacement with a randomised placebo-controlled study in COVID-19 pneumonia (in patients with pneumonia requiring oxygen but not mechanical ventilation) in Israel (NCT04502069) Updated 17 Aug 2020 |
| 06 Aug 2020 | Trial Update | RedHill Biopharma plans a phase I/II trial for COVID-19 pneumonia in Israel in August 2020 (NCT04502069) Updated 25 Oct 2020 |
| 06 Aug 2020 | Regulatory Status | Mexican Federal Committee for the Protection against Sanitary Risks (COFEPRIS) approves a CTA application for phase II/III trial for COVID-19 pneumonia [45] Updated 11 Aug 2020 |
| 31 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia (Adjunctive Treatment) in Russia, Mexico and United Kingdom (PO) before July 2020 [39] (NCT04467840) Updated 20 Aug 2020 |
| 22 Jul 2020 | Regulatory Status | RedHill Biopharma submits a clinical trial application (CTA) to the Mexican Federal Committee for the Protection against Sanitary Risks (COFEPRIS) and the Brazilian Health Regulatory Agency (ANVISA) for a phase II/III trial for COVID-19 pneumonia Updated 24 Jul 2020 |
| 16 Jul 2020 | Trial Update | RedHill Biopharma plans a phase II/III trial for COVID-19 pneumonia (Adjunctive treatment) in Russia, Mexico, Italy, Brazil, USA, United kingdom and additional EU countries (PO, Capsule) (NCT04467840) [46] Updated 25 Oct 2020 |
| 16 Jul 2020 | Regulatory Status | Israeli Ministry of Health approves CTA for clinical trial in patient with severe COVID-19 pneumonia [46] Updated 17 Jul 2020 |
| 16 Jul 2020 | Regulatory Status | The Ministry of Health of the Russian Federation approves a CTA application for a phase II/III trial for COVID-19 pneumonia [46] Updated 17 Jul 2020 |
| 16 Jul 2020 | Trial Update | RedHill Biopharma plans a clinical trial for COVID-19 pneumonia in Israel [46] Updated 17 Jul 2020 |
| 02 Jul 2020 | Phase Change - II | Phase-II clinical trials in COVID-19 pneumonia (Adjunctive treatment) in USA (PO) (NCT04414618) Updated 19 Nov 2020 |
| 02 Jul 2020 | Phase Change - II | RedHill Biopharma initiates enrolment in a phase IIa trial in COVID-19 pneumonia (Adjunctive-treatment) in Israel (PO) (NCT04414618) Updated 12 Jun 2020 |
| 29 Jun 2020 | Regulatory Status | The MHRA approves CTA application for opaganib in COVID-19 pneumonia [47] Updated 01 Jul 2020 |
| 24 Jun 2020 | Scientific Update | Efficacy and adverse data from a compassionate use programme in COVID-19 pneumonia released by RedHill Biopharma [69] Updated 29 Jun 2020 |
| 22 Jun 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in Cholangiocarcinoma presented at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [23] Updated 28 Jul 2020 |
| 19 Jun 2020 | Regulatory Status | RedHill Biopharma submits a Clinical trial application (CTA) to the UK Medicines & Healthcare Products Regulatory Agency (MHRA) and the Italian Medicines Agency (AIFA) for a phase II/III trial for COVID-19 pneumonia [48] Updated 23 Jun 2020 |
| 10 Jun 2020 | Regulatory Status | RedHill Biopharma submits a Clinical trial application (CTA) to the Ministry of Health of the Russian Federation for a phase II/III trial for COVID-19 pneumonia [49] Updated 12 Jun 2020 |
| 08 May 2020 | Regulatory Status | The US FDA approves IND application for opaganib in Pneumonia associated with COVID-19 pneumonia [59] [60] Updated 12 May 2020 |
| 30 Apr 2020 | Scientific Update | Preliminary efficacy data from a clinical trial in COVID-19 pneumonia released by RedHill Biopharma [64] Updated 30 Apr 2020 |
| 21 Apr 2020 | Trial Update | RedHill Biopharma plans a phase IIa trial for treatment of patients with COVID-19 pneumonia in the US (PO) [61] Updated 21 Apr 2020 |
| 20 Apr 2020 | Regulatory Status | RedHill Biopharma submits an IND application of opaganib to the US FDA for Pneumonia in USA [57] Updated 28 Apr 2020 |
| 17 Apr 2020 | Regulatory Status | RedHill Biopharma submits an IND application to the FDA for COVID-19 pneumonia in the US [61] Updated 21 Apr 2020 |
| 13 Apr 2020 | Scientific Update | Adverse events and efficacy data from a clinical trial in COVID-19 pneumonia released by RedHill Biopharma [66] Updated 16 Apr 2020 |
| 06 Apr 2020 | Phase Change - Clinical | Clinical trials in COVID-19 pneumonia in Israel (PO), before April 2020 - compassionate use programme [67] [66] Updated 13 Apr 2020 |
| 06 Apr 2020 | Regulatory Status | Italian National Institute for Infectious Diseases and Central Italian Ethics Committee approves compassionate use of opaganib for COVID-19 pneumonia in Italy [67] Updated 13 Apr 2020 |
| 06 Apr 2020 | Trial Update | RedHill Biopharma plans a clinical trial under compassionate use of opaganib for COVID-19 pneumonia in Italy [67] Updated 13 Apr 2020 |
| 13 Mar 2020 | Phase Change - Preclinical | Preclinical trials in COVID-19 pneumonia in Israel (PO) [19] Updated 18 Mar 2020 |
| 10 Mar 2020 | Phase Change - II | Phase-II clinical trials in Prostate cancer (Hormone refractory, Combination therapy, Metastatic disease, Second-line therapy or greater) in USA (PO) (NCT04207255) Updated 18 Mar 2020 |
| 28 Dec 2019 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Solid-tumours(Late-stage disease) in USA (PO, Capsule) Updated 28 Dec 2019 |
| 20 Dec 2019 | Trial Update | Medical University of South Carolina in collaboration with National Cancer Institute (NCI) plans a phase II trial for Prostate cancer (Combination therapy, Metastatic disease, Hormone refractory) in February 2020 (NCT04207255) Updated 18 Mar 2020 |
| 30 Sep 2019 | Trial Update | Redhill Biopharma withdraws a phase-II for Liver cancer (Late-stage disease, Second-line therapy or greater) in USA (PO) prior to enrollment as the trial is being rewritten for a different disease population [77] (NCT02939807) Updated 22 May 2023 |
| 12 Sep 2019 | Phase Change - Suspended(II) | Suspended - Phase-II for Liver cancer (Late-stage disease, Second-line therapy or greater) in USA (PO) as the trial is being rewritten for a different disease population (NCT02939807) Updated 17 Sep 2019 |
| 16 May 2019 | Trial Update | RedHill Biopharma Limited terminates a phase I/II ABC-103 trial in Multiple myeloma (Second-line therapy or greater) in USA due to expiration of National Cancer Institute (NCI) funding (PO) (NCT02757326) Updated 28 May 2019 |
| 14 Nov 2018 | Scientific Update | Efficacy and adverse events data from a phase Ib/II trial in Multiple myeloma and pharmacodynamics data from preclinical studies in Cancer released by RedHill Biopharma [106] Updated 21 Nov 2018 |
| 07 Mar 2018 | Phase Change - II | Phase-II clinical trials in Cholangiocarcinoma (Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater, Combination therapy) in USA (PO), before March 2020 (NCT03377179) Updated 18 Mar 2020 |
| 07 Mar 2018 | Phase Change - II | Phase-II clinical trials in Cholangiocarcinoma (Late-stage disease, Inoperable/Unresectable, Monotherapy, Second-line therapy or greater) in USA (PO) [17] (NCT03377179) Updated 27 Dec 2017 |
| 31 Jan 2018 | Trial Update | Redhill Biopharma completes a phase I ABC-109 trial in healthy volunteers prior in 2018 [77] Updated 22 May 2023 |
| 30 Jan 2018 | Trial Update | RedHill Biopharma initiates an expanded-access programme for Cholangiocarcinoma in Germany(NCT03414489) Updated 01 Feb 2018 |
| 01 Jan 2018 | Trial Update | Redhill Biopharma initiates enrolment in a phase I ABC-109 trial in healthy volunteers prior to 2018 [77] Updated 22 May 2023 |
| 22 Dec 2017 | Active Status Review | Phase-I development in Solid tumours (Late-stage disease) is ongoing in USA (PO, Capsule) [17] Updated 27 Dec 2017 |
| 05 Dec 2017 | Trial Update | RedHill Biopharma Limited withdraws a phase I/II trial prior to enrolment due to lack of recruitment in Diffuse large B cell lymphoma (Second-line therapy or greater) in USA (PO) (NCT02229981) Updated 20 Dec 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Solid-tumours(Late-stage disease) in USA (PO, Capsule) Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Acute radiation syndrome in USA (PO) Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Inflammatory-bowel-disease in USA (PO) Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Osteoarthritis in USA (PO) Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Rheumatoid-arthritis in USA (PO) Updated 04 Nov 2017 |
| 18 Sep 2017 | Phase Change - Clinical | Clinical trials in Cancer (Combination therapy) in USA (PO) [128] Updated 28 Sep 2017 |
| 18 Sep 2017 | Patent Information | RedHill Biopharma receives patent allowance for Yeliva® and Mesupron in USA [128] Updated 20 Sep 2017 |
| 10 Aug 2017 | Trial Update | RedHill plans a phase II ABC-105 trial for Ulcerative colitis in fourth quarter of 2017 [97] Updated 22 May 2023 |
| 10 Aug 2017 | Trial Update | RedHill Biopharma plans a phase IIa trial for Cholangicarcinoman fourth quarter of 2017 [97] Updated 27 Dec 2017 |
| 13 Apr 2017 | Other | Chemical structure information added Updated 13 Apr 2017 |
| 04 Apr 2017 | Regulatory Status | ABC 294640 receives Orphan Drug status for Cholangiocarcinoma in USA [14] Updated 07 Apr 2017 |
| 29 Nov 2016 | Scientific Update | Pharmacodynamics data from preclinical trials in Solid tumours at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR-2016) [113] Updated 29 Dec 2016 |
| 21 Nov 2016 | Licensing Status | ABC 294640 is available for licensing as of 21 Nov 2016. www.redhillbio.com [114] Updated 24 Nov 2016 |
| 05 Oct 2016 | Phase Change - II | Phase-II clinical trials in liver cancer (Second-line therapy or greater, Late-stage disease) in USA (PO) [78] Updated 07 Oct 2016 |
| 12 Sep 2016 | Trial Update | RedHill Biopharma plans a phase Ib trial for Mucositis (Prevention) in Israel [9] Updated 14 Sep 2016 |
| 08 Sep 2016 | Phase Change - I/II | Phase-I/II clinical trials in Multiple myeloma (Second-line therapy or greater) in USA (PO) [108] Updated 12 Sep 2016 |
| 26 Jul 2016 | Trial Update | RedHill Biopharmaplans three phase I/II trials for Multiple oncology, inflammatory and gastrointestinal indications [96] Updated 02 Aug 2016 |
| 21 Jun 2016 | Scientific Update | Final positive efficacy and adverse events data from a phase I trial in Solid tumours released by RedHill BioPharma [81] Updated 24 Jun 2016 |
| 04 May 2016 | Trial Update | RedHill Biopharma plans a phase II trial for liver cancer (Second-line therapy or greater, Late-stage disease) [79] Updated 09 May 2016 |
| 10 Mar 2016 | Phase Change - Preclinical | Preclinical trials in Cholangiocarcinoma in USA before March 2016 (PO) [24] Updated 15 Mar 2016 |
| 26 Oct 2015 | Scientific Update | Top-line adverse events and pharmacodynamics data from a phase I trial in Solid tumours (Late-stage disease) released by RedHill Biopharma [89] Updated 29 Oct 2015 |
| 22 Oct 2015 | Company Involvement | RedHill BioPharma receives SBIR grant from National Cancer Institute for ABC 294640 development in Prostate cancer [10] Updated 27 Oct 2015 |
| 10 Sep 2015 | Trial Update | RedHill BioPharma plans a phase II trial for Multiple myeloma (Second-line therapy or greater) in USA [11] Updated 10 Sep 2015 |
| 09 Sep 2015 | Company Involvement | RedHill BioPharma receives SBIR grant from National Cancer Institute for ABC 294640 development in Multiple myeloma [11] Updated 10 Sep 2015 |
| 01 Jul 2015 | Trial Update | RedHill Biopharma completes a phase I trial in Solid tumours (Late-stage disease) in USA (NCT01488513) Updated 03 Sep 2015 |
| 07 May 2015 | Trial Update | RedHill Biopharma plans a phase II trial for Inflammatory-GI diseases and Cancer [101] Updated 06 Jun 2015 |
| 31 Mar 2015 | Licensing Status | RedHill Biopharma acquires ABC 294640 from Apogee Biotechnology Corporation [12] Updated 04 Apr 2015 |
| 01 Jan 2015 | Phase Change - Preclinical | Preclinical trials in Prostate cancer (Hormone refractory) in USA (PO) [84] Updated 07 Sep 2015 |
| 01 Dec 2014 | Trial Update | Apogee Biotechnology completes enrolment in a phase-I clinical trial in Solid tumours (late-stage disease) in USA (PO) (NCT01488513) Updated 17 Jun 2015 |
| 15 Oct 2014 | Trial Update | Apogee Biotechnology Corporation plans a phase I/II trial for Diffuse large B-cell lymphoma in USA (NCT02229981) Updated 15 Oct 2014 |
| 01 Oct 2013 | Phase Change - Preclinical | Preclinical trials in Acute radiation syndrome and rheumatoid arthritis in USA (PO) Updated 09 Oct 2013 |
| 01 Oct 2013 | Scientific Update | Interim efficacy, safety and pharmacokinetics data from a phase I trial in Solid tumours (late-stage disease) released by Apogee Biotechnology Corporation [91] Updated 09 Oct 2013 |
| 02 Aug 2011 | Phase Change | Early research in Radiation injuries in USA (PO) Updated 02 Aug 2011 |
| 01 Aug 2011 | Phase Change - I | Phase-I clinical trials in Solid tumours (late-stage disease) in USA (PO) Updated 18 Jan 2012 |
| 11 Nov 2010 | Phase Change - Preclinical | Preclinical trials in Osteoarthritis in USA (PO) Updated 08 Dec 2010 |
| 11 Nov 2010 | Scientific Update | Pharmacodynamics data from a preclinical study in Rheumatoid arthritis presented at the 74th Annual Scientific Meeting of the American College of Rheumatology and the 45th Annual Meeting of the Association of Rheumatology and Health Professionals (ACR/ARHP-2010) [115] Updated 08 Dec 2010 |
| 11 Nov 2010 | Regulatory Status | US FDA approves IND application for ABC 294640 in Cancer [95] Updated 11 Nov 2010 |
| 19 Nov 2009 | Scientific Update | Pharmacodynamics and pharmacokinetics data from a preclinical trial in Cancer presented at the 21st AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (AACR-NCI-EORTC-2009) [130] Updated 09 Dec 2009 |
| 03 Nov 2009 | Phase Change - Preclinical | Preclinical trials in Liver disorders in USA (unspecified route) Updated 23 Nov 2009 |
| 03 Nov 2009 | Scientific Update | Pharmacodynamics data from a preclinical trial in hepatic ischaemic-reperfusion injury presented at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD-2009) [116] Updated 23 Nov 2009 |
| 16 Apr 2008 | Scientific Update | Preclinical pharmacokinetics data presented at the 99th Annual Meeting of the American Association for Cancer Research (AACR-2008) [117] Updated 30 Apr 2008 |
| 18 Nov 2005 | Phase Change - Preclinical | Preclinical trials in Inflammatory bowel disease in USA (PO) Updated 08 Dec 2005 |
| 23 Jul 2003 | Phase Change - Preclinical | Preclinical trials in Cancer in USA (unspecified route) Updated 23 Jul 2003 |
References
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RedHill Provides R&D Update.
Media Release -
RedHill's Opaganib Selected by the NIH Radiation and Nuclear Countermeasures Program.
Media Release -
RedHill Biopharma Provides H1/22 Highlights and Q3/22 Estimates.
Media Release -
RedHill and Kukbo Enter Oral Opaganib License for COVID-19 in South Korea.
Media Release -
RedHill Biopharma Further Expands Opaganib Manufacturing Capacity for COVID-19 with Cosmo Pharmaceuticals.
Media Release -
COSMO PHARMACEUTICALS STRENGTHENS PARTNERSHIP WITH REDHILL BIOPHARMA WITH MANUFACTURING AGREEMENT FOR MOVANTIK, RHB-204 AND OPAGANIB.
Media Release -
RedHill Biopharma Strengthens Partnership with Cosmo Pharmaceuticals with Manufacturing Agreements for Movantik and RHB-204.
Media Release -
RedHill Biopharma Announces Partnerships to Expand Manufacturing for COVID-19 Therapeutic Candidate Opaganib.
Media Release -
RedHill Biopharma Announces Research Collaboration with Stanford University for YELIVA(TM).
Media Release -
RedHill Biopharma Announces National Cancer Institute Grant Awarded to Apogee Biotechnology Corp. for YELIVA(TM) (ABC294640) Prostate Cancer Research.
Media Release -
RedHill Biopharma Announces $2 Million National Cancer Institute Grant for YELIVA(TM) (ABC294640) Phase II Study for Multiple Myeloma.
Media Release -
RedHill Biopharma Acquires Phase II First-in-Class Oral Small Molecule SK2 Inhibitor From Apogee Biotech.
Media Release -
BARDA supports development of new drugs to treat radiation injury.
Media Release -
RedHill Biopharma Receives FDA Orphan Drug Designation for YELIVA(R) for the Treatment of Cholangiocarcinoma.
Media Release -
RedHill Biopharma Announces Advancement to Second Stage of Phase IIa Study with YELIVA(R)for Cholangiocarcinoma.
Media Release -
RedHill Biopharma Provides Semi-Annual Business Update.
Media Release -
RedHill Biopharma Announces Initiation of Phase IIa Study with ABC294640 (YELIVA(R)) for Cholangiocarcinoma at Mayo Clinic and MD Anderson.
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RedHill Biopharma Reports First Quarter 2021 Financial Results and Operational Highlights.
Media Release -
RedHill Biopharma Provides Update on Opaganib (Yeliva(R)).
Media Release -
RedHill Biopharma Provides Q3/2020 Results and Highlights, Including 300% Talicia Prescription Growth.
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A Phase I/IIA Study of ABC294640 Alone and in Combination With Hydroxychloroquine Sulfate in the Treatment of Patients With Advanced, Unresectable Intra-hepatic, Perihilar and Extra-Hepatic Cholangiocarcinoma
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Vasquez D, Campbell NA, Asumda FZ, Fathi R, Ben-Yair VK, Levitt ML, et al. Mechanistic Effects of Upamostat and Opaganib in Cholangiocarcinoma Cell Lines. AASLD-2022 2022; abstr. 4438.
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Asumda FZ, Hassan MA, Kim YH, Campbell NA, Luo X, O'Brien DR, et al. Effects of upamostat and opaganib on cholangiocarcinoma patient derived xenografts. AACR-II-2020 2020; abstr. 3078 / 12.
Available from: URL: https://www.abstractsonline.com/pp8/#!/9045/presentation/5462 -
RedHill Biopharma Announces Peer-Reviewed Publication Demonstrating Therapeutic Potential of YELIVA(Tm) in Cholangiocarcinoma Cancer.
Media Release -
RedHill Biopharma Announces Last Patient Randomized in Part A of Ongoing Phase 2/3 COVID-19 Study of Once-Daily Oral RHB-107 in Non-Hospitalized Patients.
Media Release -
RedHill announces effective in vitro inhibition of the omicron variant by its oral COVID-19 drug candidate opaganib.
Media Release -
RedHill Biopharma Reports that Opaganib Mechanism Not Impacted by Viral Spike-Protein Mutations, Including Omicron Mutations.
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RedHill Biopharma Reports Second Quarter 2021 Financial Results and Operational Highlights.
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RedHill Biopharma Announces Compassionate Use Treatment with Opaganib of first COVID-19 Patients in Switzerland.
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RedHill Biopharma Reports Top-Line Data from Opaganib Phase 2/3 Study in Severe COVID-19 Patients.
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Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia
ctiprofile -
RedHill Biopharma Completes Enrollment of Oral Opaganib Phase 2/3 COVID-19 Study.
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RedHill Biopharma Announces Planned Expansion of Opaganib Global Phase 2/3 COVID-19 Study to the U.S.USA - English .
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RedHill Biopharma Announces Positive DSMB Futility Review for Phase 2/3 COVID-19 Study of Opaganib.
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RedHill Biopharma's Phase 2/3 COVID-19 trial of opaganib undergoes fourth DSMB review with unanimous recommendation for continuation.
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RedHill Announces Unanimous DSMB Recommendation to Continue Phase 2/3 COVID-19 Study with Opaganib.
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RedHill Biopharma Completes Enrollment for COVID-19 U.S. Phase 2 Study with Opaganib - Data Expected in the Coming Weeks.
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RedHill Biopharma's Second COVID-19 Candidate, RHB-107, Cleared by FDA for Phase 2/3 Study in Symptomatic COVID-19 Disease.
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RedHill Biopharma Provides Q2/2020 Financial Results and Operational Highlights.
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RedHill Biopharma to Host Second Quarter Financial Results and Business Highlights Conference Call and Webcast on August 13, 2020.
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RedHill Biopharma Announces Positive Recommendation from Independent Committee to Continue U.S. Phase 2 COVID-19 Study, and Approval of COVID-19 Phase 2/3 Study in Italy.
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RedHill Biopharma Receives Allowances for U.S. Patent Applications Covering Opaganib and RHB-107 for COVID-19.
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RedHill Biopharma gibt bekannt, dass der letzte Patient die Phase 2/3-COVID-19-Studie mit oral verabreichtem Opaganib beendet hat.
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Brazil Approves RedHill Biopharmas Phase 2/3 COVID-19 Study with Opaganib.
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RedHill Biopharmas Phase 2/3 COVID-19 Study Approved in Mexico.
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RedHill Biopharma Receives Approval for Phase 2/3 COVID-19 Study in Russia.
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RedHill Biopharma Receives Approval for COVID-19 Phase 2/3 Study with Opaganib in the UK.
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RedHill Biopharma Expands Opaganib COVID-19 Phase 2/3 Study with Clinical Trial Applications in Italy and UK.
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RedHill Biopharma Submits COVID-19 Clinical Trial Application for Phase 2/3 Study with Opaganib.
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RedHill Biopharma Announces Last Patient Out for Phase 2/3 COVID-19 Study of Oral Opaganib.
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RedHill Biopharma Announces First Patient Dosed in U.S. Phase 2/3 COVID-19 Outpatient Study with RHB-107.
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RedHill Biopharma Reports Further Analysis of Phase 2/3 Data Including a 62% Reduction in Mortality with Oral Opaganib in Moderately Severe COVID-19 Patients.
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RedHill Announces Additional Analysis of Phase 2/3 Results with Orally Administered Opaganib Showing 62% Reduction in Mortality in Moderately Disease Patients with COVID-19.
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Heidelberg Pharma Reports on First Half-Year 2022.
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Winthrop KL, Skolnick AW, Rafiq AM, Beegle SH, Suszanski J, Koehne G, et al. ABC-110: Opaganib, an Oral Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: A Randomized, Double-blind, Placebo-controlled Phase 2A Study, in Adult Subjects Hospitalized with SARS-CoV-2 Positive Pneumonia (NCT: 04414618). ASM-FEMS-WMF-2021 2021; abstr. N/A.
Available from: URL: https://www.abstractsonline.com/pp8/#/9286/presentation/10399 -
RedHill Biopharma Announces Presentation of Positive Oral Opaganib Phase 2 Data in COVID-19.
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RedHill Biopharma Announces Agreement with NIAID to Evaluate RHB-107 Against COVID-19.
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RedHill Biopharma Announces Positive Top-Line Safety and Efficacy Data from Phase 2 COVID-19 Study of Opaganib.
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Opaganib (ABC294640) successfully treats patients with COVID-19 in Israel, Clinical trial approved in the U.S.
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RedHill Biopharma Receives FDA Approval for COVID-19 Clinical Study with Opaganib in the U.S.
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IND for COVID-19 with Opaganib Submitted to the FDA by RedHill Biopharma.
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Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia
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Treatment of COVID-19 With Opaganib in Patients With Pneumonia Requiring Oxygen But Not Mechanical Ventilation
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Six COVID-19 Patients Treated with RedHills Opaganib Under Compassionate Use Show Objective Clinical Improvement.
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Additional Update on COVID-19 Compassionate Use with Opaganib in Israel Provided by RedHill Biopharma.
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RedHill Biopharma Provides Initial Update from its Opaganib COVID-19 Compassionate Use Program in Israel.
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RedHill Biopharma Announces Approval of Compassionate Use of Opaganib for COVID-19 in Italy.
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Compassionate Use of Opaganib in Patients With Severe COVID-19
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Publication of Data from Severe COVID-19 Patients Shows Substantial Benefit to Patients Treated with RedHills Opaganib Compared to Matched Case-Control Group.
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RedHill Biopharmas Opaganib COVID-19 Study Passes Second Independent Committee Review.
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RedHill Biopharma's Opaganib Demonstrates Strong Inhibition of COVID-19 Delta Variant.
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RedHill Biopharma's Opaganib Inhibits COVID-19 Variants in Preclinical Study.
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RedHill Biopharmas Opaganib Demonstrates Complete Inhibition of SARS-CoV-2.
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RedHill's Oral Broad-Acting Antivirals, Opaganib and RHB-107, Inhibit Dominant Omicron Sub-Variant BA.5.
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RedHill and U.S. Army Announce Opaganib's Ebola Virus Disease Survival Benefit in U.S. Army-Funded In-Vivo Study.
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RedHill and U.S. Army Announce Opaganib and RHB-107 Combinations with Remdesivir Show Distinct Synergistic Effect Against Ebola.
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Redhill Biopharma Form 20-K. Internet-Doc 2023;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/1553846/000155837023007149/rdhl-20221231x20f.htm -
RedHill Biopharma Announces Initiation of Phase II Study with YELIVA(TM) in Hepatocellular Carcinoma at the Medical University of South Carolina.
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RedHill Biopharma Announces National Cancer Institute Grant Supporting YELIVA(TM) Phase II Hepatocellular Carcinoma Study.
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RedHill Biopharma Provides Full-Year 2019 Financial Results and Operational Highlights.
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RedHill Biopharma Announces Positive Final Results with Primary and Secondary Endpoints Met in Phase 1 Study with YELIVA(TM) in Advanced Solid Tumors.
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A Phase II Study of ABC294640 in Patients With Advanced Hepatocellular Carcinoma Who Have Progressed on Sorafenib
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A Phase II Study of the Addition of Opaganib to Androgen Antagonists in Patients With Prostate Cancer Progression on Enzalutamide or Abiraterone
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RedHill Biopharma Announces Peer-Reviewed Publication Demonstrating Therapeutic Potential of ABC294640 (YELIVA(TM)) in Prostate Cancer.
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RedHill's Opaganib Protects Against Radiation-Induced Lung Inflammation and Fibrosis - New Publication.
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RedHill Biopharma Announces Positive FDA Meeting Regarding Opaganib for Acute Nuclear Radiation Syndrome.
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RedHill Biopharma Announces Positive New Data with Opaganib for Nuclear Radiation Injury.
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RedHill's Phase 2/3 COVID-19 Candidate Opaganib Reduces ARDS-Related Blood Clotting in Preclinical Model.
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RedHill Biopharma Announces Positive Top-line Results from YELIVA(TM) (ABC294640) Phase I Study in Advanced Solid Tumors.
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RedHill Biopharma Announces Last Patient Visit in the Phase I Study With YELIVA(Tm) (ABC294640) for Advanced Solid Tumors.
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Apogee to present phase 1 clinical trial results at the 2013 Molecular Targets and Cancer Therapeutics meeting.
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A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors
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RedHill Biopharma Announces YELIVA(R) (ABC294640) Abstract Presentation at the 2017 Cholangiocarcinoma Foundation Annual Conference.
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RedHill Biopharma Announces Peer-Reviewed Publication of the Positive YELIVA(Rm) Phase I Study Results in Advanced Solid Tumors.
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Apogee Biotechnology Corporation to Launch Phase I Clinical Studies.
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RedHill Biopharma Reports 2016 Second Quarter Financial Results.
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RedHill Biopharma Provides 2017 Semi-Annual Business Update - 10 Aug 2017 .
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RedHill Biopharma Provides 2017 Semi-Annual Business Update.
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RedHill Biopharma Provides Update on Development Pipeline and Expected Timing for RHB-105 Phase III Top-Line Results.
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RedHill Biopharma Reports Results for the First Quarter of 2015.
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RedHill Biopharma to Host Investor Webcast Forum Following Completion of RHB-105 Dosing in Phase III Study.
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A Phase II study to evaluate ABC294640 as a radioprotectant to prevent mucositis and radiation enhancer in cancer patients undergoing radiotherapy
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RedHill Biopharma Reports Results for the Second Quarter of 2015.
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RedHill Biopharma Initiates Phase I/II Study of ABC294640 for Refractory Lymphoma.
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An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
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RedHill Biopharma Announces Presentation on YELIVA(R) (opaganib) for Multiple Myeloma at EORTC-NCI-AACR Symposium.
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RedHill Biopharma Announces First Patient Dosed in Phase Ib/II Study with YELIVA(R) for Multiple Myeloma.
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RedHill Biopharma Announces Phase Ib/II Study with YELIVA(TM) Initiated for Multiple Myeloma at a Leading U.S. Academic Medical Center.
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RedHill Biopharma Provides 2016 R&D Update.
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A Phase Ib/II Safety and Efficacy Study of ABC294640 in Patients With Refractory or Relapsed Multiple Myeloma Who Have Previously Been Treated With Proteasome Inhibitors and Immunomodulatory Drugs
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RedHill Biopharma Announces Q1/22 Highlights: On Track for Positive Cash from Operations in H2/22.
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RedHill Biopharma's Opaganib Demonstrates Significant Decrease of Kidney Fibrosis.
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Smith C, Maines L, Schrecengost R, Zhuang Y, Keller S, Smith R, et al. Antitumor and anti-inflammatory effects of the sphingosine kinase-2 inhibitor ABC294640 in combination with radiation. EORTC-NCI-AACR-2016 2016; abstr. 171.
Available from: URL: http://www.ecco-org.eu/Events/ENA2016 -
RedHill Biopharma Announces YELIVA(TM) (ABC294640) Poster Presentation at the 2016 EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium.
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Fitzpatrick LR, Green C, Maines LW, Smith CD. Experimental Osteoarthritis in Rats Is Attenuated by Treatment with a Selective Inhibitor of Sphingosine Kinase 2. 74th-ACR-45th-ARHP-2010 2010; abstr. 1480.
Available from: URL: http://www.rheumatology.org -
Shi Y. Role of Spingosine Kinase in Mitochondrial Dysfunction and Inflammation after Hepatic Ischemia-reperfusion in Mice. 60th-AASLD-2009 2009; abstr. 1249.
Available from: URL: http://www.aasld.org/thelivermeeting/Pages/default.aspx -
Smith CD, Wen X, Wang W, Zhuang Y, Green CL, Maines LW. Pharmacokinetics, biodistribution and metabolism of the sphingosine kinase inhibitor ABC294640. 99th-Ann-Meet-Am-Assoc-Can-Res 2008;1163.
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French KJ, Smith CD, Zhuang Y, Xia Z, Maines LW, Upson JJ, et al. Development of orally-available inhibitors of sphingosine kinase with anticancer and anti-inflammatory activity. 17th-AACR-NCI-EORTC 2005;248 (plus poster) abstr. C195.
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RedHill's Opaganib Selected for Evaluation by BARDA and NIH Countermeasures Programs.
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RedHill Announces Additional U.S. Government Funding for Opaganib Nuclear Countermeasure Development.
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RedHill Biopharma Announces $10 Million Bought Deal Offering.
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RedHill Biopharma's Opaganib Awarded COVID-19 Grant by State of Pennsylvania.
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RedHill Announces New USPTO Notice of Patent Allowance for Opaganib and EU Patent Grant for RHB-102 (BEKINDA(Rm)).
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RedHill's RHB-102 (BEKINDA(Rm)) and Opaganib Granted New Patents in Oncology Setting.
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RedHill's Oral Broad-Acting Antiviral, Opaganib, Granted New COVID-19 Treatment Patent.
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RedHill Biopharma Announces Two New U.S. Patents Covering Opaganib for Ebola Virus and RHB-104 for Crohn's.
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RedHill Biopharma Receives U.S. Patent Allowance Covering Opaganib and RHB-107 Combination.
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RedHill Biopharma Receives Notice of Allowance for a New U.S. Patent Covering its Combination Therapy for Hard-to-Treat Cancers.
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RedHill Biopharma's Oral Opaganib Significantly Improves Viral Clearance in Phase 2/3 Study in Severely Ill Hospitalized COVID-19 Patients.
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Beljanski V, Knaak C, Zhuang Y, Smith C. Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. 21st-AACR-NCI-EORTC-2009 2009; abstr. B251.
Available from: URL: http://www.aacr.org/home/scientists/meetings--workshops/molecular-targets-and-cancer-therapeutics.aspx -
RedHill Biopharma Provides H2/2019 R&D Update.
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French KJ, Schrecengost RS, Lee BD, Zhuang Y, Smith SN, et al. Discovery of high-affinity inhibitors of human sphingosine kinase. 94th-AACR 2003;686 (plus poster) abstr. 3459.
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RedHill Biopharma Reports 2016 Fourth Quarter and Full-Year Financial Results.
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