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13 results on '"Levitt, Mark L."'

1. Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts

Author

Asumda, Faizal Z., primary, Campbell, Nellie A., additional, Hassan, Mohamed A., additional, Fathi, Reza, additional, Vasquez Rico, Daniella F., additional, Kiem, Melanie, additional, Vang, Ethan V., additional, Kim, Yo Han, additional, Luo, Xin, additional, O’Brien, Daniel R., additional, Buhrow, Sarah A., additional, Reid, Joel M., additional, Moore, Michael J., additional, Ben-Yair, Vered Katz, additional, Levitt, Mark L., additional, Leiting, Jennifer L., additional, Abdelrahman, Amro M., additional, Zhu, Xinli, additional, Lucien, Fabrice, additional, Truty, Mark J., additional, and Roberts, Lewis R., additional

Published
2024
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2. Recent Progress in the Development of Opaganib for the Treatment of Covid-19

Author

Smith,Charles D, Maines,Lynn W, Keller,Staci N, Katz Ben-Yair,Vered, Fathi,Reza, Plasse,Terry F, and Levitt,Mark L

Subjects
Drug Design, Development and Therapy
Abstract

Charles D Smith,1 Lynn W Maines,1 Staci N Keller,1 Vered Katz Ben-Yair,2 Reza Fathi,2 Terry F Plasse,2 Mark L Levitt2 1Apogee Biotechnology Corporation, Hummelstown, PA, USA; 2RedHill Biopharma LTD, Tel Aviv, IsraelCorrespondence: Charles D Smith, Apogee Biotechnology Corporation, 1214 Research Blvd, Suite 2015, Hummelstown, PA, 17036, USA, Tel +1 843 814 9257, Email CDSmith@apogee-biotech.comAbstract: The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Recent work demonstrates that opaganib also has antiviral activity against several viruses including SARS-CoV-2. A recently completed multinational Phase 2/3 clinical trial of opaganib in patients hospitalized with Covid-19 demonstrated that opaganib can be safely administered to these patients, and more importantly, resulted in a 62% decrease in mortality in a large subpopulation of patients with moderately severe Covid-19. Furthermore, acceleration of the clearance of the virus was observed in opaganib-treated patients. Understanding the biochemical mechanism for the anti-SARS-CoV-2 activity of opaganib is essential for optimizing Covid-19 treatment protocols. Opaganib inhibits three key enzymes in sphingolipid metabolism: sphingosine kinase-2 (SK2); dihydroceramide desaturase (DES1); and glucosylceramide synthase (GCS). Herein, we describe a tripartite model by which opaganib suppresses infection and replication of SARS-CoV-2 by inhibiting SK2, DES1 and GCS. The potential impact of modulation of sphingolipid signaling on multi-organ dysfunction in Covid-19 patients is also discussed.Keywords: opaganib, ABC294640, sphingolipid, sphingosine kinase, dihydroceramide desaturase, glucosylceramide synthase

Published
2022

3. Opaganib in Coronavirus Disease 2019 Pneumonia: Results of a Randomized, Placebo-Controlled Phase 2a Trial

Author

Winthrop, Kevin L, primary, Skolnick, Alan W, additional, Rafiq, Adnan M, additional, Beegle, Scott H, additional, Suszanski, Julian, additional, Koehne, Guenther, additional, Barnett-Griness, Ofra, additional, Bibliowicz, Aida, additional, Fathi, Reza, additional, Anderson, Patricia, additional, Raday, Gilead, additional, Eagle, Gina, additional, Ben-Yair, Vered Katz, additional, Minkowitz, Harold S, additional, Levitt, Mark L, additional, and Gordon, Michael S, additional

Published
2022
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6. Abstract 3078: Effects of upamostat and opaganib on cholangiocarcinoma patient derived xenografts

Author

Asumda, Faizal Z., primary, Hassan, Mohamed A., additional, Kim, Yo Han, additional, Campbell, Nellie A., additional, Luo, Xin, additional, O'Brien, Daniel R., additional, Buhrow, Sarah A., additional, Reid, Joel M., additional, Moore, Michael J., additional, Ben-Yair, Vered Katz, additional, Fathi, Reza, additional, Levitt, Mark L., additional, Lucien-Matteoni, Fabrice, additional, Leiting, Jennifer L., additional, Truty, Mark J., additional, and Roberts, Lewis R., additional

Published
2020
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9. Abstract B30: A phase 1 open label, dose-escalation trial evaluating the safety and tolerability of EF-022, macrophage activator, in subjects with advanced solid malignancies

Author

Golan, Talia, primary, Berger, Raanan, additional, Ackerstein, Aliza, additional, Raskin, Steve, additional, Lesokhin, Alexander M., additional, Sidransky, David, additional, Levitt, Mark L., additional, Gadassi, Hana, additional, Yogev, Uri, additional, and Shahar, Michal, additional

Published
2015
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11. Interleukin-2 induces development of dendritic cells from cord blood CD34+ cells

Author

Bykovskaja, Svetlana N, primary, Buffo, Mary Jo, additional, Bunker, Mark, additional, Zhang, Haifan, additional, Majors, Alana, additional, Herbert, Mary, additional, Lokshin, Anna, additional, Levitt, Mark L, additional, Jaja, Andrew, additional, Scalise, Deborah, additional, Kosiban, Deborah, additional, Evans, Carol, additional, Marks, Stanley, additional, and Shogan, Jeffrey, additional

Published
1998
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12. Ceramide does not act as a general second messenger for ultraviolet-induced apoptosis.

Author

Jiong Deng, Haifan Zhang, Kloosterboer, Freke, Yong Liao, Klostergaard, Jim, Levitt, Mark L., and Mien-Chie Hung

Subjects
SECOND messengers (Biochemistry), APOPTOSIS
Abstract

Presents a study which characterized the possible role of second messenger ceramide in ultraviolet-induced apoptosis in both E1A transfectants and parental cells. Review of related literature; Materials and methods used; Results.

Published
2002
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13. Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO 2 Requirements.

Author

Neuenschwander FC, Barnett-Griness O, Piconi S, Maor Y, Sprinz E, Assy N, Khmelnitskiy O, Lomakin NV, Goloshchekin BM, Nahorecka E, Joaquim Westheimer Calvacante A, Ivanova A, Vladimirovich Zhuravel S, Yurevna Trufanova G, Bonora S, Saffoury A, Mayo A, Shvarts YG, Rizzardini G, Sobroza de Mello R, Pilau J, Klinov A, Valente-Acosta B, Olegovich Burlaka O, Bakhtina N, Bar-Meir M, Nikolaevich Shishimorov I, Oñate-Gutierrez J, García Rincón CI, Ivanovna Martynenko T, Hajjar LA, Carolina Nazare de Mendonca Procopio A, Simon K, Gabriel Chaves Santiago W, Fronczak A, Roberto Hoffmann Filho C, Hussein O, Aleksandrovich Martynov V, Chichino G, Blewaska P, Wroblewski J, Saul Irizar Santana S, Felipe Ocampo Agudelo A, Barczyk A, Lask Gerlach R, Campbell E, Bibliowicz A, Fathi R, Anderson P, Raday G, Klein M, Fehrmann C, Eagle G, Ben-Yair VK, and Levitt ML

Abstract

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO 2 ) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO 2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO 2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p -value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p -value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p -value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO 2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Published
2024
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