AbstractMyelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML) are closely related diseases of haematopoietic stem cells (HSCs), characterized by ineffective terminal differentiation, effacement of normal blood cell production and accumulation of neoplastic cells, known as blasts, in the bone marrow, peripheral blood, and other tissues. In the past ten years it has become apparent that cancers are not composed of uniform populations of cancer cells. Instead, the great majority of the cells making up a cancer have very limited ability to undergo cell division, or have completely lost the ability to divide - only a minority of cells, known as cancer stem cells, retain the ability to divide in an unlimited way. To identify potential therapeutic targets, we studied the molecular signature of leukemia stem cells identifying the orphan nuclear receptor NR2F6 as a potential therapeutic target for differentiation therapy for MDS and AML. We've previously shown that NR2F6 is over expressed in patients with myelodysplastic syndromes and acute myeloid leukemia. In vitro, overexpression of NR2F6 inhibits differentiation of cell lines and primary bone marrow cells. In vivo, overexpression of EAR-2 using a retroviral vector in a chimeric mouse model lead to a condition that resembled myelodysplastic syndrome with hypercellular bone marrow, increased blasts, abnormal localization of immature progenitors, morphological dysplasia of the erythroid lineage and a competitive advantage over wild-type cells, that eventually leads to AML in a subset of the mice, or after secondary-transplantation. While overexpression of NR2F6 in 100% transduced bone marrow grafts that were sorted by flow cytometry prior to transplantation lead to a rapidly fatal erythroleukemia that was characterized by a block in terminal differentiation, pancytopenia and profound anemia. Furthermore, silencing of NR2F6 expression in human and mouse-leukemia cell lines causes terminal differentiation and death by apoptosis. This forms the basis of the therapeutic concept that we wished to develop further, by identifying gene-silencing methods that could be advanced to preclinical development for the treatment of myelodysplastic syndrome and acute leukemia.The discovery of the role of NR2F6 in leukemogenesis and the induction of differentiation of leukemia cell lines following silencing of NR2F6 expression suggests that this is a logical therapeutic target for differentiation therapy using gene silencing technology. Hence, we wished to show that silencing of NR2F6 using DiffronC, an oligonucleotide based gene-silencing technology, in primary mouse hematopoietic cells promoted terminal differentiation. Herein, we show that while DiffronC did not significantly reduce the number of colony forming units, it did significantly increase colony size. This was especially striking in cultures grown under erythroid conditions, where we observed a 3.21 increase in the number of cells per colony. We then showed that DiffronC reduced the clonal longevity of bone marrow cells: In replating experiments we observed a significant decrease in secondary colonies in cells treated with NR2F6 shRNA. Furthermore, DiffronC resulted in a drastic reduction in KSL stem and progenitor cells after six days of ex vivo culture, and caused a dramatic decline in lineage negative cells, and a concurrent increase in cells expressing the myeloid markers CD11b and Gr-1, suggesting that they had differentiated into cells of the neutrophil lineage. This was confirmed by examination of the cytomorphology of the bone marrow cultures. Taken together, these results establish that NR2F6 is a negative regulator of terminal differentiation of the hematopoietic lineage and lays the foundation for use of gene silencing technology using DiffronC as differentiation therapy for diseases with blocked differentiation such as leukemia and myelodysplastic syndromes.DisclosuresIchim: Entest BioMedical Inc: Employment, Equity Ownership, Research Funding; Regen BioPharma Inc: Employment, Equity Ownership, Patents & Royalties, Research Funding. Koos:Entest BioMedical Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Regen BioPharma Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Wells:Alexion: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

01 Aug 2015·Cancer Research

Abstract 5349: Discovery of retinoic acids as low affinity inhibitors of the leukemia stem cell target NR2F6

Author: Wells, Richard A. ; Koos, David ; Ichim, Thomas ; Ichim, Christine V. ; Dervovic, Dzana ; Chan, Lap Shu Alan

AbstractMany human cancers are composed of heterogeneous populations of cells. While most cancer cells have a limited ability to divide, growth of the tumor is carried out by a small population of cancer stem cells, and hence represent the true target of effective anti-cancer therapy.To identify potential therapeutic targets, we previously studied the molecular signature of leukemia stem cells. Our work has led to the discovery of the orphan nuclear receptor NR2F6 (EAR-2) as a potential leukemia stem cell therapeutic target. We have previously shown that NR2F6 is over expressed in patients with acute leukemia and related bone marrow cancers, and that exogenous expression of NR2F6 in mouse bone marrow cells causes acute leukemia in vivo. Furthermore, silencing of NR2F6 expression in human and mouse-leukemia cell lines causes terminal differentiation and death by apoptosis. The discovery of the role of NR2F6 in leukemogenesis and the effects of silencing NR2F6 expression on leukemia cells suggests that this protein is a logical candidate as a therapeutic target in acute leukemia and related disorders for differentiation therapy. This forms the basis of the therapeutic concept that we wished to develop further, by identifying small molecule modulators of NR2F6 function.We hence developed a screening tool that was used to survey the ability of known nuclear receptor ligands to modulate NR2F6 activity. We constructed a hybrid receptor, comprising the NR2F6 ligand binding domain fused to the Gal4 DNA-binding domain. The hybrid receptor was co-transfected into HeLa cells along with a reporter plasmid in which a Gal4 regulatory sequence was placed upstream of a luciferase gene running off a constitutive promoter. The transfected cells were treated with candidate ligands and assayed for luciferase activity by luminometer. Of the 20 nuclear receptor ligands assessed none showed a significant effect at low concentrations (up to 1μM). However, we identifying 9-cis retinoic acid and, to a lesser extent, all-trans retinoic as low affinity ligands for NR2F6 since they were able to show a dose-dependent effect that we began to observe at 20μM.Retinoic acid and its analogues have long been studied in the context of chemoprevention and differentiation therapy based on their anti-proliferative, pro-apoptotic, and ability to induce differentiation. We have now commenced the search for a high affinity small molecular inhibitor of NR2F6 activity by screening commercially available libraries that contain compounds with similar chemical structure to retinoic acid using the luciferase-based assay developed here.Citation Format: Christine V. Ichim, Lap Shu Alan Chan, Dzana Dervovic, David Koos, Richard A. Wells, Thomas Ichim. Discovery of retinoic acids as low affinity inhibitors of the leukemia stem cell target NR2F6. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5349. doi:10.1158/1538-7445.AM2015-5349

News (Medical) associated with Regen Biopharma, Inc.

23 Sep 2024

·www.globenewswire.com

Regen BioPharma, Inc. to Present at the Emerging Growth Conference on September 25, 2024, At 4 pm Eastern Time

Regen BioPharma, Inc. invites individual and institutional investors as well as advisors and analysts, to attend its real-time, interactive presentation at the Emerging Growth Conference. SAN DIEGO, CA, Sept. 23, 2024 (GLOBE NEWSWIRE) -- Regen BioPharma, Inc. (OTC PINK: RGBP) (OTC PINK: RGBPP), a biotechnology company advancing a diverse pre-clinical pipeline spanning cell therapies, RNA vaccines, RNA and DNA therapeutics and small molecule drugs will be presenting at the Emerging Growth Conference on September 25, 2024 (https://emerginggrowth.com/conference/). This live, interactive online event will give existing shareholders and the investment community the opportunity to interact with the Company’s CEO, Dr. David Koos, in real time. Please ask your questions during the event and Dr. Koos and his team will do their best to get through as many of them as possible. “We plan to use this time to update our shareholders on our fiscal and scientific goals for the upcoming year, discuss our progress on current programs and timeline regarding our anticipated HemaXellerate clinical phase I,” says Dr. David Koos, CEO and Chairman of the Company. Regen BioPharma, Inc. will be presenting at 4:00 pm to 4:10 Eastern time on Wednesday September 25, 2024. Please register here to ensure you are able to attend the conference and receive any updates that are releasedhttps://goto.webcasts.com/starthere.jsp?ei=1677125&tp_key=64e020ccee&sti=rgbp If attendees are not able to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com. About the Emerging Growth Conference The Emerging Growth conference is an effective way for public companies to present and communicate their new products, services and other major announcements to the investment community from the convenience of their office, in a time efficient manner. The Conference focus and coverage includes companies in a wide range of growth sectors, with strong management teams, innovative products & services, focused strategy, execution, and the overall potential for long term growth. Its audience includes potentially tens of thousands of individual and institutional investors, as well as investment advisors and analysts. About Regen BioPharma Inc.: Regen BioPharma, Inc. is a publicly traded biotechnology company (PINK: RGBP) and (PINK: RGBPP). The Company is focused on the immunology and immunotherapy space. The Company is focused on rapidly advancing novel technologies through pre-clinical and Phase I/ II clinical trials. Currently, the Company is focused on mRNA and small molecule therapies for treating cancer and autoimmune disorders. Additional information on Regen BioPharma is available at http://www.regenbiopharmainc.com. Disclaimer: This news announcement may contain forward-looking statements. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking statements. The risks and uncertainties to which forward looking statements are subject include, but are not limited to, the effect of government regulation, competition and other material risks. CONTACT INFORMATION: Regen BioPharma Inc.David R. Koos, Ph.D.Chairman & Chief Executive Officer+1-619-722-5505 Phone+1-619-330-2328 FaxEmail: david.koos@regenbiopharmainc.com or david.koos@regenbiopharma.com X (formerly twitter): https: //x.com/TheRegenBio

Phase 1Immunotherapy

07 May 2024

·www.prnewswire.com

Regen BioPharma, Inc. to Present at the Emerging Growth Conference on May 9, 2024

Regen BioPharma, Inc. invites individual and institutional investors as well as advisors and analysts, to attend its real-time, interactive presentation at the Emerging Growth Conference. SAN DIEGO, Calif., May 7, 2024 /PRNewswire/ -- Regen BioPharma, Inc. (OTC PINK: RGBP) (OTC PINK: RGBPP), a biotechnology company advancing a diverse pre-clinical pipeline spanning cell therapies, RNA vaccines, RNA and DNA therapeutics and small molecule drugs will be presenting at the Emerging Growth Conference on May 9, 2024 (). This live, interactive online event will give existing shareholders and the investment community the opportunity to interact with the Company's CEO, Dr. David Koos, in real time. Please ask your questions during the event and Dr. Koos and his team will do their best to get through as many of them as possible. "We plan to use this time to update our shareholders on our Phase 1 clinical study-ready HemaXellerate and our preclinical DuraCAR programs," says Dr. David Koos, CEO and Chairman of the Company. Regen BioPharma, Inc. will be presenting at 1:45 - 2:15 Eastern time on Thursday May 9, 2024. Please register here to ensure you are able to attend the conference and receive any updates that are released . If attendees are not able to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com. About the Emerging Growth Conference The Emerging Growth conference is an effective way for public companies to present and communicate their new products, services and other major announcements to the investment community from the convenience of their office, in a time efficient manner. The Conference focus and coverage includes companies in a wide range of growth sectors, with strong management teams, innovative products & services, focused strategy, execution, and the overall potential for long term growth. Its audience includes potentially tens of thousands of individual and institutional investors, as well as investment advisors and analysts. About Regen BioPharma Inc.: Regen BioPharma, Inc. is a publicly traded biotechnology company (PINK: RGBP) and (PINK: RGBPP). The Company is focused on the immunology and immunotherapy space. The Company is focused on rapidly advancing novel technologies through pre-clinical and Phase I/ II clinical trials. Currently, the Company is focused on mRNA and small molecule therapies for treating cancer and autoimmune disorders. Additional information on Regen BioPharma is available at . Disclaimer: This news announcement may contain forward-looking statements. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking statements. The risks and uncertainties to which forward looking statements are subject include, but are not limited to, the effect of government regulation, competition and other material risks. CONTACT INFORMATION: Regen BioPharma Inc. David R. Koos, Ph.D. Chairman & Chief Executive Officer +1-619-722-5505 Phone +1-619-330-2328 Fax Email: [email protected] Twitter (now X): SOURCE Regen BioPharma Inc.

Phase 1Immunotherapy

05 Mar 2024

·www.biospace.com

Regen BioPharma, Inc. to Present at the Emerging Growth Conference on March 7, 2024

Regen BioPharma, Inc. invites individual and institutional investors as well as advisors and analysts, to attend its real-time, interactive presentation at the Emerging Growth Conference. SAN DIEGO, March 5, 2024 /PRNewswire/ -- Regen BioPharma , Inc. (OTC PINK: RGBP) (OTC PINK: RGBPP), a biotechnology company advancing a diverse pre-clinical pipeline spanning cell therapies, RNA vaccines, RNA and DNA therapeutics and small molecule drugs will be presenting at the Emerging Growth Conference on March 7, 2024 ( ). This live, interactive online event will give existing shareholders and the investment community the opportunity to interact with the Company's CEO, Dr. David Koos, in real time. Please ask your questions during the event and Dr. Koos and his team will do their best to get through as many of them as possible. "We plan to use this time to update our shareholders on recent scientific results around our DuraCAR product and will discuss subsequent steps to expand on these findings ," says Dr. David Koos, CEO and Chairman of the Company. Regen BioPharma, Inc. will be presenting at 3:10-3:20 Eastern time on Wednesday March 7, 2024. Please register here to ensure you are able to attend the conference and receive any updates that are released . If attendees are not able to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com. About the Emerging Growth Conference The Emerging Growth conference is an effective way for public companies to present and communicate their new products, services and other major announcements to the investment community from the convenience of their office, in a time efficient manner. The Conference focus and coverage includes companies in a wide range of growth sectors, with strong management teams, innovative products & services, focused strategy, execution, and the overall potential for long term growth. Its audience includes potentially tens of thousands of individual and institutional investors, as well as investment advisors and analysts. About Regen BioPharma Inc.: Regen BioPharma, Inc. is a publicly traded biotechnology company (PINK: RGBP) and (PINK: RGBPP). The Company is focused on the immunology and immunotherapy space. The Company is focused on rapidly advancing novel technologies through pre-clinical and Phase I/ II clinical trials. Currently, the Company is focused on mRNA and small molecule therapies for treating cancer and autoimmune disorders. Additional information on Regen BioPharma is available at . Disclaimer: This news announcement may contain forward-looking statements. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking statements. The risks and uncertainties to which forward looking statements are subject include, but are not limited to, the effect of government regulation, competition and other material risks. CONTACT INFORMATION: Regen BioPharma Inc. David R. Koos, Ph.D. Chairman & Chief Executive Officer +1-619-722-5505 Phone +1-619-330-2328 Fax Email: david.koos@regenbiopharma.com Twitter (now X): Company Codes: OTC-BB:RGBAD, OTC-BB:RGBP, OTC-BB:RGBPD, OTC-BB:RGBPP, OTC-PINK:RGBAD, OTC-PINK:RGBP, OTC-PINK:RGBPD, OTC-PINK:RGBPP, OtherOTC:RGBP, OtherOTC:RGBPP

100 Deals associated with Regen Biopharma, Inc.

100 Translational Medicine associated with Regen Biopharma, Inc.

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

HemaXcellerate	Anemia, Aplastic More	Phase 1
DuraCAR(Regen Biopharma) ( NR2F6 )	Neoplasms More	Preclinical
DiffronC ( NR2F6 )	Solid tumor More	Preclinical
KimerApt	Solid tumor More	Preclinical
RG-NAE005 ( NR2F6 )	Autoimmune Diseases More	Preclinical

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