Photomicrograph of human nerve cell.
“The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Inhibits Growth of Human Glioblastoma, Reduces Akt/mTOR Activities, and Modulates GSC Cell-Renewal Properties". Colapietro Alessandro, Yang Peiying, Rossetti Alessandra, Mancini Andrea, Vitale Flora, Martellucci Stefano, Conway Tara L., Chakraborty Sharmistha, Marampon Francesco, Mattei Vincenzo, Gravina Giovanni Luca, Biordi Assunta Leda, Wei Daoyan, Newman Robert A., Festuccia Claudio. Frontiers in Pharmacology.
PBI sponsored research at the University of Texas at San Antonio has demonstrated that PBI-05204 leads to a marked reduction in neuroinflammtion in brain microglial cells in vitro. Importantly, when fed to mice orally the PBI drug also produces a significant reduction in accumulation of beta-amyloid plaques within the brains of specifically bred transgenic mice that develop Alzheimer’s-like disease. Taken together ,these recent findings suggest that further exploration of the utility of PBI-05204 for neurodegenerative diseases like Alzheimer's is warranted.
A recent 2020 publication has shown that oleandrin effectively and selectively targets human breast cancer cells without affecting normal breast epithelial cells. The selectivity is based in part on the relative content of Na,K-ATPase alpha-3 subunit as previously shown by Phoenix Biotechnology scientists.
Camargo Pharmaceutical Services, LLC offers support to Phoenix Biotechnology Inc. in the development of PBI-05204, for the treatment of various tropical diseases eligible to receive priority review vouchers.
Phoenix Biotechnology has entered the Patents For Humanity awards competition sponsored by the United States Patent & Trademark Office. The program recognizes innovators who use game-changing technology to meet global humanitarian challenges. It provides business incentives for reaching those in need: winners receive an acceleration certificate to expedite select proceedings at the USPTO, as well as public recognition of their work. The awards showcase how patent holders with vision are pioneering innovative ways to provide affordable, scalable, and sustainable solutions for the less fortunate. The essay submitted by the company in support of its entry is reproduced below, in its entirety.
New research findings presented in November at the Italian Cancer Society’s 61st annual meeting in Naples, Italy confirm the ability of Phoenix Biotechnology’s drug PBI-05204 to act synergistically with coadministration of temozolamide and radiotherapy to kill Glioblastoma Multiforme (GBM) in mice with orthotopically implanted human GBM cells. These data are currently being prepared for publication.
"The Botanical Glycoside Oleandrin Inhibits Human T-cell Leukemia Virus Type-1 Infectivity and Env-Dependent Virological Synapse Formation". Tetiana Hutchison, Laçin Yapindi, Aditi Malu, Robert A Newman, K Jagannadha Sastry and Robert Harrod. Journal of Antivirals & Antiretrovirals, (2019) Volume 11, Issue 3
"Oleandrin sensitizes human osteosarcoma cells to cisplatin by preventing degradation of the copper transporter 1". Yong L, Ma Y, et al. Phtyother. Res. 2019 May.
This article shows that oleandrin enhances or synergizes with the standard of care chemotherapy agent cisplatin against osteosarcoma (bone) cancer.
Importance: Phoenix Biotechnology's drug PBI-05204 contains oleandrin as one of its main active ingredients and we have previously shown that it acts in a synergistic manner with chemotherapy drugs against a variety of different types of human malignant disease. New data being prepared for publication now shows the PBI-05204 is synergistic with Temozolamide and radiotherapy against glioblastoma, a difficult to treat form of brain cancer.
"Oleandrin and its derivative Odoroside A, both cardiac glycosides, exhibit anticancer effects by inhibiting invasion via suppressing the STAT-3 signaling pathway". Intnl. J. Mol. Sci. 2018, 19(11); 3350. Ko YS, Rugira T, Jin H, Park SW and Kim HJ.
This article demonstrates that oleandrin and odoroside A, both of which are contained within PBI-05204, are effective at inhibiting the invasive capacity of human breast cancer cells. In addition, they reduce breast cancer stem cell activity.
HTLV-1. HTLV stands for Human T-cell Leukemia Virus. It is a retrovirus that infects a type of white blood cell called a T-cell or T-lymphocyte. HTLV-1 can be passed on through infected blood, semen, vaginal fluids, rectal secretions, breast milk and organ transplants. Two of the more severe consequences of HTLV-1 infection are ATLL (adult T-cell leukemia/lymphoma) and HAM/TSP (HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis) which is an inflammation of the cells of the spinal cord that can cause stiffness and weakness of the legs, lower leg and backache, a ‘weak’ bladder, constipation and erectile dysfunction. In other words, consequences that severely impact the quality of one’s life. Now, research conducted with colleagues at Southern Methodist University, has shown that PBI-05204 (as well as oleandrin) has the ability to reduce the potential of HTLV-1 virus to ‘synapse’ with cells thus blocking the infection. A manuscript describing this exciting research is presently being prepared.
Glioblastoma research. In two independent labs, research has now established significant benefit of PBI-05204 against human glioblastoma (GBM) in mice with xenograft tumors. The response to PBI-05204 alone when administered orally was significant, but the response when PBI-05204 was used in combination with temozolamide and radiotherapy was outstanding. Mechanistic and related pharmacology studies are currently underway.
Neurodegenerative research. Ongoing research has now demonstrated that PBI-05204 reduces oxidative damage and neuronal cell death as well as neuroinflammation. The work, conducted at The University of Texas at San Antonio, showed that PBI’s lead drug reduced the expression of pro-inflammatory cytokines. The data clearly shows that PBI-05204 reduces neuroinflammatory reactions in microglial cells and suggest its therapeutic potential for the treatment of Alzheimer’s disease. In vivo studies are currently underway.
An independent review article written by Turkish investigators has been published titled: “Neuroprotective and tumoricidal activities of cardiac glycosides. Could oleandrin be a new weapon against stroke and glioblastoma?” Int. J. Neuroscience 2018 Feb 15: 1-13. [Comment from Dr. Newman: This article cites PBI’s research].
A research program with Dr. Claudio Festuccia (Department of Experimental Medicine, University of L’Quila, Italy) is currently underway exploring the relative effects of PBI’s oleander extract combined with radiotherapy against glioblastoma.
A research project with Dr. Xiao-Nan Li, Baylor College of Medicine and Brain Tumor Program/Texas Children’s Hospital is showing encouraging results of PBI’s oleander extract both when used alone as well as in combination with radiotherapy against glioblastoma (brain cancer). Studies are ongoing.
The U.S. Army Medical Research Institute together with Dr. R. Newman (PBI Chief Science Officer) presented research with PBI’s oleander extract at the 9th International Symposium on Filoviruses held in Marburg, Germany. The data presented showed highly significant inhibition of Ebola virus. Research is ongoing with respect to this important antiviral discovery.
The U.S. Army Medical Research Institute of Infectious Disease (Ft. Detrick, MD) has completed promising preclinical research with PBI’s lead oleander extract and found it to be highly effective against Ebola and Marburg viruses.
An independent research group from Sapienza University in Italy has reported that oleandrin (key component in PBI-05204) significantly increased mouse survival and reduced brain tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by brain derived neurotrophic factor (BDNF). [Comment from Dr. Newman: These studies corroborated PBI’s findings on the important role of their drug for brain tumors and neurodegenerative disease]. The Journal of Neuroscience April, 2017; 37(14):3926-3939.
Trade Article written by David Holley at Xconomy.
PBI is extremely pleased to announce an expansion of their Scientific Advisory Board to include world class experts in antiviral, neurodegenerative disease and cancer related research fields. Please see the SAB tab on this web page to view current SAB members, institutional affiliations and brief biographies.
Because the active principle ingredient in PBI-05204 readily crosses the blood brain barrier (BBB) it has the potential to benefit malignant disease that resides in the brain. PBI has initiated research on pediatric glioblastoma multiforma (GBM) together with Dr. Xiao-Nan Li (Brain Tumor Program, Texas Children’s Cancer Center, Baylor College of Medicine) and Dr. Peiying Yang (Univ. Texas M. D. Anderson Cancer Center). Initial preclinical research with PBI-05204 against human GBM growing in vitro as well as in murine brain tissue has been very encouraging. There are few, if any, current effective drugs available for treatment of pediatric GBM.
PBI is in the process of concluding its Phase II trial of PBI-05204 against advanced, drug refractory pancreatic cancer. This disease is often diagnosed only after it has metastasized throughout the body making any truly effective treatment difficult. PBI-05204 was evaluated in this patient population at five clinical sites across the USA. In addition to once again demonstrating the safety of our drug, we are pleased to announce that a partial response and several stable disease designations were obtained.
Due to initial success of PBI-05204 against HIV in preclinical studies PBI has expanded its antiviral research program to include new research of the effectiveness of its drug against viruses such as cytomegalovirus (CMV), respiratory syncytial virus (RSV), as well as truly deadly viruses for which there are at present no effective therapies. Initial preclinical results against all of these viruses look promising suggesting that PBI-05204 may serve as a novel broad-spectrum antiviral agent.
The article titled "Pharmacokinetics and Comparative Effects of Frondosides in Pancreatic Cancer" by: Jasem Al Shemaili, Khatija Parekh, Robert Newman, Björn Hellman, Carl Woodward, Abdu Adem, Peter Collin, Thomas E Adrian is now published in Marine Drugs.
Publication: "Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke" by Michael Van Kanegan, Denise Dunn, Linda Kaltenbach, Bijal Shah, Dong Ning He, Daniel McCoy, Peiying Yang, Jiangnan Peng, Shen Li, Lin Du, Robert Cichewicz, Robert A. Newman, and Donald Lo. Nature Scientific Reports.
PBI is pleased to announce an excellent rate of accrual of advanced pancreatic cancer patients to their Phase II clinical study. To date, 37 patients of the target goal of 50 have been entered on the study with no serious adverse events attributable to the investigational drug. Given that our drug is an oral capsule and does not cause debilitating side effects or hair loss, it is an attractive alternative to patients who would rather not have to deal with frequent trips to the hospital for intravenous injections. For these patients, maintaining quality of life is an important consideration. The goal of our PBI-05204 clinical trial is to provide evidence of efficacy and safety in this patient population. To date there is evidence of activity in this heavily pretreated patient population and we are anticipating completion of the trial by the end of the year. The trial is being conducted at five prestigious clinical institutions within the USA.
Research with colleagues at Duke University continues to reveal important brain mediated benefits in response to PBI-05204. Not only have our two published studies shown an increase in brain derived neurotrophic factor (BDNF) but research now being prepared for publication shows a significant response of ARE (antioxidant response elements) in brain tissue which is associated with protection of neurons from oxidative injury.
NIH has expressed an interest in exploring the potential of PBI-05204 to alleviate the extreme fatigue often associated in cancer patients undergoing radiation therapy. The reasoning behind this is that brain derived neurotrophic factor (BDNF) levels have been observed to fall in these patients. Given that PBI’s drug increases BDNF levels in brain tissue, it is hypothesized that this may be of benefit and increase the quality of life in cancer patients who receive radiation therapy. Phoenix Biotechnology is delighted that NIH has recognized the value of our drug for this purpose and will work closely with them in these ongoing studies.
We are pleased to announce that by the end of this month there will be 5 clinical sites open across the USA that are approved to enroll patients to our Phase II trial for treatment of advanced pancreatic cancer. These sites include Vanderbilt University Medical Center (Nashville, TN), Virginia Mason Medical Center (Seattle, WA), Virginia Cancer Specialists (Fairfax, VA), Florida Hospital Tampa (Tampa, FL) and HonorHealth (Scottsdale, AZ). Further information on the trial and criteria for enrollment eligibility can be obtained at www.clinicaltrials.gov and searching under "PBI-05204".
In late December, 2014 the FDA approved of our plans to take PBI-05204 forward into clinical Phase II trials. The clinical study titled "A Phase II, Single-arm, Open-Label, Bayesian Adaptive Efficacy and Safety Study of PBI-05204 in Patients with Stage IV Metastatic Pancreatic Adenocarcinoma" will be conducted at multiple sites within the USA including such prestigious institutions as Vanderbilt University Medical Center. It is anticipated that the first patient will be enrolled this summer.
A manuscript describing the therapeutic effects of PBI-05204 against human pancreatic cancer implanted orthotopically (within the pancreas) in immunocompromised mice has been accepted for publication in Investigational New Drugs. The article shows that the botanical drug PBI-05204 is effective in a dose dependent manner and superior to the standard-of-care approved drug known as gemcitabine. The title and authors are: PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits growth of human pancreatic cancer via targeting the PI3K/mTOR pathway. Pan Y., Rhea, P.,Tan L, Lee H. J., Ravoori M., Addington C.,Gagea M., Kundra V, Kim S-J, Newman R.A., and Yang P. Read Article
A manuscript describing the results of the Phase I trial of PBI-05204 conducted at the Univ. Texas M. D. Anderson Cancer Center has been published in Investigational New Drugs. The title and authors are: First-In-Human Study of PBI-05204, an Oleander-Derived Inhibitor of Akt, FGF-2, NF-kB and p70S6K, In Patients with Advanced Solid Tumors. D.S. Hong, H. Henary, G.S. Falchook, A. Naing, S. Fu, S. Moulder, J.J. Wheler, A. Tsimberidou, J.B. Durand, R. Khan, M. Johansen, P. Yang, R.A. Newman and R. Kurzrock. Investigational New Drugs, June, 2014. PMID: 24919855
Additional testing of PBI-05204 against patient derived tumors is being conducted at Rational Therapeutics (San Diego, CA). The purpose of the research is to determine relative activity of PBI's lead drug against pancreatic cancer for which very few active drugs exist. In addition, the relative activity of PBI-05204 in combination with standard of care cancer chemotherapeutic agents is also being examined. Initial results are encouraging.
Publication: BDNF Mediates Neuroprotection against Oxygen-Glucose Deprivation by the Cardiac Glycoside Oleandrin. Michael J. Van Kanegan, Dong Ning He, Denise E. Dunn, Peiying Yang, Robert A. Newman, Anne E. West and Donald C. Lo. The Journal of Neuroscience, 15 January 2014, 34(3): 963-968; doi: 10.1523/JNEUROSCI.2700-13.2014.
Presentation Abstract: PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits the growth of human pancreatic cancer in a Panc-1 orthotopic model by down-regulation of PI3k/mTOR pathways. Dr. Robert A. Newman, our Chief Science Officer will be presenting at the Beaujon Conference in Paris, France, on February 13-15.
Presentation Abstract: PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits the growth of human pancreatic cancer in a Panc-1 orthotopic model by down-regulation of PI3k/mTOR pathways. Yong Pan, Sun-Jin Kim, Patrea Rhea, Carrie Cartwright, Ho Jeong Lee, Crandell Addington, Mihai Gagea, Robert A. Newman, Peiying Yang. UT MD Anderson Cancer Ctr., Houston, TX. AACR Annual Meeting 2013.
POSTER (When open please zoom-in to see the details)
Ex-Vivo Programmed Cell Death in Human Tumor Samples Produced by Exposure to PBI-05204 - Results
Publication: Nerium oleander derived cardiac glycoside oleandrin is a novel inhibitor of HIV infectivity. Singh S, Shenoy S, Nehete PN, Yang P, Nehete B, Fontenot D, Yang G, Newman RA, Sastry KJ. Fitoterapia, November 2012. PMID: 23127567
Publication: Cellular location and expression of Na+, K+-ATPase α subunits affect the anti-proliferative activity of oleandrin. Yang, P., Cartwright, C., Efuet, E., Hamilton, S. R., Wistuba, I. I., Menter, D., Addington, C., Shureqi, I. and Newman, R. A. (2012). Mol. Carcinog. doi: 10.1002/mc.21968. PMID: 23073998
Publication: Digoxin and ouabain induce the efflux of cholesterol via liver X receptor signalling and the synthesis of ATP in cardiomyocytes. Campia I, Sala V, Kopecka J, Leo C, Mitro N, Costamagna C, Caruso D, Pescarmona G, Crepaldi T, Ghigo D, Bosia A, Riganti C. Biochem. J. (2012) 447, 301–311 (Printed in Great Britain) doi:10.1042/BJ20120200. PMID: 22845468
Data: Evidence of downregulation of cholesterol and triglyceride with administration of an extract of Nerium Oleander. File
Research Article: Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. Menger L, Vacchelli E, Adjemian S, Martins I, Ma Y, Shen S, Yamazaki T, Sukkurwala AQ, Michaud M, Mignot G, Schlemmer F, Sulpice E, Locher C, Gidrol X, Ghiringhelli F, Modjtahedi N, Galluzzi L, André F, Zitvogel L, Kepp O, Kroemer G. Source INSERM, U848, F-94805 Villejuif, France. PMID: 22814852
Phoenix Biotechnology executes a seventh amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Phoenix Biotechnology enters into a research agreement with Rational Therapeutics, Inc. to conduct examination of antitumor effects of PBI-05204 on human tumor biopsy samples (an 'in vitro' Phase II study).
Publication: In vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin from Nerium oleander in brain slice-based stroke models. Dunn DE, He DN, Yang P, Johansen M, Newman RA, Lo DC. J Neurochem. 2011 Nov;119(4):805-14. PMID: 21950737
Phoenix executes a Sponsored Research Agreement with Duke University for in vivo research in animal models to study prevention of ischemic stroke using PBI-05204.
ASCO annual meeting poster presentation along with an oral format with discussion of clinical trial results of PBI-05204.
Phoenix Biotechnology executes a sixth amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Phase I Clinical Trial of PBI-05204 successfully completed at M. D. Anderson Cancer Center.
Phoenix raises >$3,000,000 from angel investors.
Phoenix Biotechnology executes a fifth amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Publication: Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na+, K+ -ATPase subunits. Lin Y, Ho DH, Newman RA. J Exp Ther Oncol. 2010;8(4):271-86. PMID: 21222360
Phoenix Biotechnology executes a fourth amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Society of Integrative Oncology (SIO) International Conference- comprehensive poster presentation with discussion.
Phoenix Biotechnology executes a third amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Publication: Oleandrin-mediated inhibition of human tumor cell proliferation: importance of Na,K-ATPase alpha subunits as drug targets. Yang P, Menter DG, Cartwright C, Chan D, Dixon S, Suraokar M, Mendoza G, Llansa N, Newman RA. Mol Cancer Ther. 2009 Aug;8(8):2319-28. PMID: 19671733
Update on Phase I trial of PBI-05204: ASCO annual meeting poster presentation with discussion.
Phoenix Biotechnology executes a Sponsored Research Agreement with Duke University for in vitro research in neurological disorders using PBI-05204 and certain discrete fractions of the whole extract.
Phoenix Biotechnology executes a second amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center.
Publication: Determinants of human and mouse melanoma cell sensitivities to oleandrin. Lin Y, Dubinsky WP, Ho DH, Felix E, Newman RA. J Exp Ther Oncol. 2008;7(3):195-205. PMID: 19066128
Phoenix raises >$3,000,000 from angel investors.
Publication: Cardiac glycosides as novel cancer therapeutic agents. Newman RA, Yang P, Pawlus AD, Block KI. Mol Interv. 2008 Feb;8(1):36-49. Review. PMID: 18332483
Publication: Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside. Newman RA, Kondo Y, Yokoyama T, Dixon S, Cartwright C, Chan D, Johansen M, Yang P. Integr. Cancer Ther. 2007 Dec;6(4):354-64. PMID: 18048883
Phoenix executes an amendment to its Sponsored Research Agreement with M. D. Anderson Cancer Center
USFDA approves Phoenix IND 73,624 application to conduct a Phase I Trial with PBI-05204, a patented supercritical extract of Nerium oleander, in patients with advanced cancer.
Phoenix enters into contract with Quintiles, Inc. to act as Clinical Research Organization for "An Open Label Phase I Trial of PBI-05204 in Advanced Cancer Patients" to be conducted at M. D. Anderson Cancer Center.
Phoenix Biotechnology, Inc. executes a share exchange agreement with Nerium Biotechnology, Inc. by which Nerium Biotechnology acquires all the Latin American operations of Phoenix.
Publication: Oleandrin-mediated oxidative stress in human melanoma cells. Newman RA, Yang P, Hittelman WN, Lu T, Ho DH, Ni D, Chan D, Vijjeswarapu M, Cartwright C, Dixon S, Felix E, Addington C. J Exp Ther Oncol. 2006;5(3):167-81. PMID: 16528968
Focus on Health: Oleander plant shows promise as cancer-fighter.
Wednesday, June 22, 2005
By Dr. Karen Johnson / KHOU 11 News - Houston
Phoenix raises >$5,000,000 from angel investors
Phoenix executes a Sponsored Research Agreement with Univ. Texas M. D. Anderson Cancer Center for research into the pharmacology and anticancer effects of Nerium oleander.
Phoenix Biotechnology is designated a "Super Star" by the San Antonio Technology Accelerator Initiative.
Phoenix Biotechnology acquires the assets of Anvirlat, Inc., a Nevada corporation, conducting pharmaceutical research in Central America on the therapeutic effects of plant extracts for patients suffering from neoplastic disease.
Phoenix Biotechnology raises >$1,000,000 from angel investors
Phoenix Biotechnology, Inc. is formed as a Texas corporation
2000 - 2002
Initial publications of pharmacology studies of Nerium oleander conducted at Univ. Texas M. D. Anderson Cancer Center include:
LC/MS/MS analyses of an oleander extract for cancer treatment. Wang X, Plomley JB, Newman RA, Cisneros A. Anal Chem. 2000 Aug 1;72(15):3547-52. PMID: 10952541
Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB. Cancer Res. 2000 Jul 15;60(14):3838-47. PMID: 10919658
Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. McConkey DJ, Lin Y, Nutt LK, Ozel HZ, Newman RA. Cancer Res. 2000 Jul 15;60(14):3807-12. PMID: 10919654
Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. Pathak S, Multani AS, Narayan S, Kumar V, Newman RA. Anticancer Drugs. 2000 Jul;11(6):455-63. PMID: 11001386
Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin. Smith JA, Madden T, Vijjeswarapu M, Newman RA. Biochem Pharmacol. 2001 Aug 15;62(4):469-72. PMID: 11448457
Composition and preliminary pharmacology studies with Anvirzel: An extract of Nerium oleander. Newman RA, Cisneros A, Felix E, Vijjeswarapu M, Lin Y, Yang P, and Azadi P. J. Herbal Pharmacotherapy. 2001 1(3):1-16
Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander. Ni D, Madden TL, Johansen M, Felix E, Ho DH, Newman RA. J Exp Ther Oncol. 2002 Sep-Oct;2(5):278-85. PMID: 12416031