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That was the PR that came out originally on April 9th, before the conference happened. I guess that pharmacy site is just now posting it too.
http://www.marketwired.com/press-release/regen-biopharma-inc-announces-small-molecule-drug-discovery-milestones-american-association-otcbb-rgbp-2008056.htm
$ RGBP $
Yes she presented at the AACR yesterday. She's also presenting that material at the 13th International Symposium on Myelodsyplastic Syndromes on May 1st, 2015. So maybe we'll hear after that?
Oral Presentation 2 Abstract: C.Ichim - NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
OR07 Oral Session
MDS and the aging stem cell: Abstracts
01-May-2015 11:00 12:00
Abstract:
NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
The hierarchical organization of leukemia suggests that discovery of the genes that encode for maintenance of the undifferentiated state of leukemia stem cells will have important clinical relevance. Using a novel single-cell approach that gave unprecedented sample purity, we identified NR2F6 (EAR-2), as a gene associated with leukemia cells that retain the ability to divide. We validated that patients with leukemia and MDS expressed higher levels of NR2F6 mRNA than healthy bone marrow, and showed that silencing of NR2F6 induced differentiation and apoptosis of a human leukemia cell line. Here we studied the roles of NR2F6 in normal hematopoiesis and in the pathogenesis of MDS and acute myelogenous leukemia (AML).
In vitro, primary bone marrow cells engineered to overexpress NR2F6 undergo a block of differentiation, but have greatly extended proliferative ability in colony assays. Overexpression of NR2F6 profoundly impaired differentiation along multiple hematopoietic lineages including the erythroid lineage. NR2F6 over-expressing bone marrow cells formed 40% fewer BFU-E colonies, but had greatly extended replating capacity in colony assays. While knockdown of NR2F6 increased the number of cells produced per BFU-E colony 300%.
In vivo, overexpression of NR2F6 in a chimeric mouse model leads to a condition that resembles MDS 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.
Normal mice transplanted with bone marrow cells from the NR2F6 chimeric mice undergo an expansion of the stem cell compartment in the transplanted mice. This observation was confirmed ex vivo: overexpression of NR2F6 maintained hematopoietic stem cells in culture, while silencing of NR2F6 induces profound differentiation of hematopoietic stem cells. Transplanted animals also developed a rapidly fatal leukemia characterized by pancytopenia, enlargement of the spleen, and infiltration of blasts into the spleen, liver and peripheral blood. Leukemic cells had an erythroblastic morphology and immunophenotype. We further observed an increase of erythroblasts in the bone marrow of preleukemia animals cells, suggesting that over-expression of NR2F6 blocks erythroid differentiation at the erythroblast stage. Mechanistically, we show that DNA binding is necessary for NR2F6 function, and that NR2F6 functions in an HDAC-dependent manner, regulating expression genes involved in erythroid differentiation.
These data establish that NR2F6 is a novel oncogene that controls hematopoietic cell fate decisions and is an ideal target for differentiation therapy of acute leukemia and MDS.
Co-authors
C. Ichim1, D. Dervovic2, D. Koos1, T. Ichim1, R. Wells3.
1Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA.
2Immunology, University of Toronto, Toronto, Canada.
3Department of Medical Oncology/Hematology Odette Cancer Center, University of Toronto and Sunnybrook Health Sciences Center, Toronto, Canada.
http://mds.kenes.com
At the very least it seems to have staved off the potential downturn the PPS was about to make. Look at the chart since it bottomed out around Feb 9th - that's the combined effect of the (approximately) 15 PRs we've seen in that time. IMO a pretty dramatic change that can't really be measured by the weight of any individual news item, but rather by the snowballing of all the recent progress.
$ RGBP $
Reminder: today's news appears for NYSE:CRL as well! Potentially some new eyes on RGBP, and at the very least a little bit of exposure.
http://money.cnn.com/news/newsfeeds/articles/marketwire/1189624.htm
$ RGBP $
That was beautiful, CV. I'm definitely excited to see them go with an acclaimed and trustworthy institution like CRL. Like you mentioned in another post, the transaction is most likely paid for with actual dollars rather than shares; unlike what may have been arranged had they used a smaller, lesser-known institution.
Whether by coincident or intent, today's news has been released on the day of Christine Ichim's presentation of her retinoic acid/NR2F6 results at the AACR. IMO, we'll see some major developments announced for this project following the other conference next week (13th I.S.M.S.). On top of that, we should expect a 10-Q (Jan 1/15 - Mar 31/15) by May 8th. An update on dCellVax mixed in somewhere also seems fitting.
$ RGBP $
SUMMARY OF HEMAXELLERATE PROGRESS (UPDATED APR 2015):
Jan 24, 2013 - Pre-clinical proof of concept and plan to file IND.
http://ih.advfn.com/p.php?pid=nmona&article=55986712
Feb 5, 2013 - Announcement that IND was filed.
http://ih.advfn.com/p.php?pid=nmona&article=56150687
Mar 18, 2013 - Regen receives IND# from FDA.
http://ih.advfn.com/p.php?pid=nmona&article=56788567
Apr 4, 2013 - FDA will send a letter outlining items which must be addressed prior to initiating clinical trials.
http://ih.advfn.com/p.php?pid=nmona&article=57035344
Jun 6, 2013 - Regen responds to FDA questions (including new data).
http://ih.advfn.com/p.php?pid=nmona&article=57897013
Jul 31, 2013 - Regen in second round of discussion with FDA on a new set of FDA comments.
http://ih.advfn.com/p.php?pid=nmona&article=58628844
Sept 26, 2013 - Agreement for pre-clinical animal trials with WP Min to address FDA comments.
http://ih.advfn.com/p.php?pid=nmona&article=59372541
Oct 31, 2013 - Cook General Biotechnology to continue producing clinical grade HemaXellerate for pre-clinial and clinical studies.
http://ih.advfn.com/p.php?pid=nmona&article=59847939
Dec 11, 2013 - Update on WP Min work regarding pre-clinical animal studies
http://ih.advfn.com/p.php?pid=nmona&article=60352616
May 12, 2014 - FDA accepted the clinical protocol and the product manufacturing information; clarification on animal safety studies was requested.
http://ih.advfn.com/p.php?pid=nmona&article=62167863
Sept 10, 2014 - Regen to submit additional safety data from a GLP-certified lab prior to initiating clinical trials.
http://www.marketwired.com/press-release/regen-biopharma-provides-update-on-hemaxellerate-ind-progress-after-conference-call-otcbb-rgbp-1945965.htm
Oct 6, 2014 - Experimental protocol submitted to FDA regarding proposed pre-clinical experiments; follow-up from previous PR.
http://www.marketwired.com/press-release/regen-biopharma-submits-experimental-protocol-fda-hemaxellerate-aplastic-anemia-trial-otcbb-rgbp-1954889.htm
Oct 14, 2014 - Dr. Amit Patel Joins Scientific Advisory Board, has experience in over 17 FDA trials; will assist Regen with HemaXellerate and dCellVax.
http://www.marketwired.com/press-release/cell-therapy-expert-dr-amit-patel-joins-regen-biopharma-inc-scientific-advisory-board-otcbb-rgbp-1957807.htm
Jan 14, 2015 - Progress update for 2015; FDA is reviewing protocols for HemaXellerate GLP safety study.
http://www.marketwired.com/press-release/regen-biopharma-inc-provides-update-on-companys-progress-areas-specialization-2015-otcbb-rgbp-1982809.htm
Mar 17, 2015 - Regen received final comments and authorization from the FDA to proceed with the GLP safety study; clinical trial anticipated to begin once GLP data is reviewed by the FDA.
http://www.marketwired.com/press-release/regen-receives-green-light-from-fda-proceed-with-glp-safety-study-support-its-hemaxellerate-otcbb-rgbp-2001028.htm
Apr 7, 2015 - Thomas Ichim will present a poster entitled "HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA" at the 13th International Symposium on Myelodysplastic Syndromes. RGBP also has two other presentations scheduled for this symposium.
http://www.marketwired.com/press-release/regen-biopharma-inc-present-multiple-presentations-13th-international-symposium-on-myelodysplastic-otcbb-rgbp-2007259.htm
Apr 13, 2015 - Selection process of potential GLP labs (for HemaXellerate safety study) narrowed down to two candidates.
http://www.marketwired.com/press-release/regen-biopharma-narrows-selection-cro-candidates-hemaxellerate-glp-safety-studies-requested-2008917.htm
Apr 22, 2015 - Regen selects Charles River Laboratories to carry out the GLP safety study for HemaXellerate. Expected to be last phase of experimentation before clinical trials can begin.
http://www.marketwired.com/press-release/regen-biopharma-inc-engages-charles-river-laboratories-initiate-fda-requested-study-otcbb-rgbp-2012279.htm
** All dates listed above refer to the date of the linked PR **
$ RGBP $
Thanks NEW, this is actually an abstract book for the 13th International Symposium on Myelodysplastic Syndromes being held April 29 - May 2, 2015. Regen will present two oral presentations and one poster presentation, as per the April 7th RGBP PR:
http://www.marketwired.com/press-release/regen-biopharma-inc-present-multiple-presentations-13th-international-symposium-on-myelodysplastic-otcbb-rgbp-2007259.htm
The abstracts have been published in Elsevier’s journal Leukemia Research. Bottom line - more eyes to see them!
Symposium website: http://mds.kenes.com/
----------
Poster Presentation Abstract: T.Ichim - HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA
30-Apr-2015 08:30 16:30
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=112483513
Oral Presentation 1 Abstract: C.Ichim - TECHNIQUE FOR ESTABLISHMENT OF LONG TERM IN VITRO CULTURES OF PRIMARY MDS CELLS
30-Apr-2015 14:00 15:30
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=112483497
Oral Presentation 2 Abstract: C.Ichim - NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
01-May-2015 11:00 12:00
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=112483492
$ RGBP $
Here's the abstract for Christine Ichim's poster presentation:
Abstract Number: 5349
Presentation Title: Discovery of retinoic acids as low affinity inhibitors of the leukemia stem cell target NR2F6
Presentation Time: Wednesday, Apr 22, 2015, 8:00 AM -12:00 PM
Location: Section 28
Poster Board Number: 9
Author Block: Christine V. Ichim1, Lap Shu Alan Chan2, Dzana Dervovic3, David Koos1, Richard A. Wells2, Thomas Ichim1. 1Regen BioPharma Inc., San Diego, CA; 2Sunnybrook Research Institute, Toronto, ON, Canada; 3University of Toronto, Toronto, ON, Canada
Abstract Body: Many 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.
Source: http://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=3682&sKey=d159ef6b-e47f-402a-9a14-1c3bbdff5bfb&cKey=711f053f-2ff6-4320-849c-62b885a1fb6f&mKey=19573a54-ae8f-4e00-9c23-bd6d62268424
***Here's also a pdf guide for Wednesday April 22nd. Her poster is listed on page 28 (or 600, depending which page numbers you go by): http://www.aacr.org/Documents/AACR_AM15_Wednesday.pdf
Just speculating; take it easy, nobody is paid around here. No they certainly don't have a history of perfectly timed PRs, or even regular communication for that matter. However, since Todd Caven's appointment as CFO in February 2015 (along with hiring of the Ichims) we've received more regular communication.
There have been at least a dozen PRs in under two months, averaging out to more than once a week. This is a massive shift from the seldom frequency they were releasing back in the BMSN and early RGBP days. I have to imagine they're more structured and putting more thought than they have before.
$ RGBP $
Yeah CV, it's curious that they would release a PR saying that the GLP study is almost underway but not quite. It might be an update timed for any interest coming off of the Cold Spring Harbor conference last week and heading into the AACR at the end of this week. Apparently we'll know within a couple weeks who was chosen for the GLP work, and hopefully a timeframe can be provided at that time as well.
Either way, today I know more about the progress of HemaXellerate than I did yesterday, so it's hard to complain.
$ RGBP $
Very interesting Mando, thanks for posting! I wonder if these are generated at the stage of IND submission, or if perhaps it means there is some closer approval than we know about. Still, we know HemaXellerate needs to go through the GLP study first, but it's promising to see things like this posted through Springer's system.
Have a great weekend
$ RGBP $
Yeah some end of week painting perhaps
bid/ask at 0.30/0.37, looking to jump back up!
That's pretty strange lol
$ RGBP $
SUMMARY OF HEMAXELLERATE PROGRESS (UPDATED APR 2015):
Jan 24, 2013 - Pre-clinical proof of concept and plan to file IND.
http://ih.advfn.com/p.php?pid=nmona&article=55986712
Feb 5, 2013 - Announcement that IND was filed.
http://ih.advfn.com/p.php?pid=nmona&article=56150687
Mar 18, 2013 - Regen receives IND# from FDA.
http://ih.advfn.com/p.php?pid=nmona&article=56788567
Apr 4, 2013 - FDA will send a letter outlining items which must be addressed prior to initiating clinical trials.
http://ih.advfn.com/p.php?pid=nmona&article=57035344
Jun 6, 2013 - Regen responds to FDA questions (including new data).
http://ih.advfn.com/p.php?pid=nmona&article=57897013
Jul 31, 2013 - Regen in second round of discussion with FDA on a new set of FDA comments.
http://ih.advfn.com/p.php?pid=nmona&article=58628844
Sept 26, 2013 - Agreement for pre-clinical animal trials with WP Min to address FDA comments.
http://ih.advfn.com/p.php?pid=nmona&article=59372541
Oct 31, 2013 - Cook General Biotechnology to continue producing clinical grade HemaXellerate for pre-clinial and clinical studies.
http://ih.advfn.com/p.php?pid=nmona&article=59847939
Dec 11, 2013 - Update on WP Min work regarding pre-clinical animal studies
http://ih.advfn.com/p.php?pid=nmona&article=60352616
May 12, 2014 - FDA accepted the clinical protocol and the product manufacturing information; clarification on animal safety studies was requested.
http://ih.advfn.com/p.php?pid=nmona&article=62167863
Sept 10, 2014 - Regen to submit additional safety data from a GLP-certified lab prior to initiating clinical trials.
http://www.marketwired.com/press-release/regen-biopharma-provides-update-on-hemaxellerate-ind-progress-after-conference-call-otcbb-rgbp-1945965.htm
Oct 6, 2014 - Experimental protocol submitted to FDA regarding proposed pre-clinical experiments; follow-up from previous PR.
http://www.marketwired.com/press-release/regen-biopharma-submits-experimental-protocol-fda-hemaxellerate-aplastic-anemia-trial-otcbb-rgbp-1954889.htm
Oct 14, 2014 - Dr. Amit Patel Joins Scientific Advisory Board, has experience in over 17 FDA trials; will assist Regen with HemaXellerate and dCellVax.
http://www.marketwired.com/press-release/cell-therapy-expert-dr-amit-patel-joins-regen-biopharma-inc-scientific-advisory-board-otcbb-rgbp-1957807.htm
Jan 14, 2015 - Progress update for 2015; FDA is reviewing protocols for HemaXellerate GLP safety study.
http://www.marketwired.com/press-release/regen-biopharma-inc-provides-update-on-companys-progress-areas-specialization-2015-otcbb-rgbp-1982809.htm
Mar 17, 2015 - Regen received final comments and authorization from the FDA to proceed with the GLP safety study; clinical trial anticipated to begin once GLP data is reviewed by the FDA.
http://www.marketwired.com/press-release/regen-receives-green-light-from-fda-proceed-with-glp-safety-study-support-its-hemaxellerate-otcbb-rgbp-2001028.htm
Apr 7, 2015 - Thomas Ichim will present a poster entitled "HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA" at the 13th International Symposium on Myelodysplastic Syndromes. RGBP also has two other presentations scheduled for this symposium.
http://www.marketwired.com/press-release/regen-biopharma-inc-present-multiple-presentations-13th-international-symposium-on-myelodysplastic-otcbb-rgbp-2007259.htm
--> Here's a link to the poster abstract
** All dates listed above refer to the date of the linked PR **
I figured it'd be a good idea to repost this for a lot of the new people coming onto the board. GLTA!
$ RGBP $
RGBP has stepped up their game over the last two months, and it's really starting to show. Between new scientific advancements and shareholder communication, this is finally feeling like a hidden gem about to burst into mainstream credibility. I'm hoping the end of April will bring updates about the HemaXellerate GLP safety study, dCellVax IND progress, and NR2F6 small molecule development (as per today's PR and recent patents).
Oh and then a 10-Q by May 8th IMO
$ RGBP $
Agreed, BMSN has the potential to be ~0.0027 at least*, in my estimation, just based on them holding RGBP. Maybe we'll see a correction when big news/big money comes in.
* Based on current RGBP PPS and share structure for RGBP and BMSN
$ RGBP BMSN $
If it does that'll be a great place to load. Chart analysis isn't always reliable for penny stocks, but in this case it's easy to see the recent uptrend we've headed into. Realize that even 0.30 is above yesterday's high.
This month is all about conferences! Great to see Regen getting out there into the scientific community. Looks like they have C. Ichim to thank for much of that.
$ RGBP $
I'm showing .35 on the mobile iHub app. It always seems to be a little buggy though. For instance, it's been showing a closing price of .1550 for about a month now lol
Don't worry though, we'll get to .35...and beyond!
$ RGBP $
Ah, my bad then! Just got caught up wondering what's with the activity today, when it was yesterday that we actually got a PR but saw little movement. I agree, things are slowly building in several aspects of the company and this will hopefully reflect in the PPS soon...and maybe once a few IND approvals go through!
GLTY
$ RGBP $
Not to be "that guy", but the conference starts at 7:30pm tonight.
http://meetings.cshl.edu/meetings/2015/rnatx15.shtml
Sure it could be related, but perhaps there's another (better!) reason for the PPS spike...
$ RGBP $
Bid x Ask just cranked to .25/.29
$ RGBP $
1st quarter ended Mar 31, so my guess is first week of May.
$ RGBP $
Yes let's hope that's the case, otherwise the introduction of those shares would hurt the PPS if there is no buying pressure. Either way, I agree with you that 2015 is shaping up to be the best year this company (in any of its forms) has seen thus far.
Also hoping that we'll see a GLP Safety Study PR for HemaXellerate to know that has begun and its anticipated deadline. Last piece of the HemaXellerate puzzle, as it were.
$ RGBP $
GLP safety study estimate: 6 months IMO, based on a quote from T.Ichim's HemaXellerate poster abstract:
"...assessment of safety and efficacy will be performed at 1, 3, and 6 months..."
Poster Presentation Abstract: T.Ichim - HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA
PO01 Poster Session
Poster Session 1: Clinical trials- non-transplant
30-Apr-2015 08:30 16:30
Abstract: 019
HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA
Aplastic anemia, defined by pancytopenia with a hypocellular bone marrow, is believed to be the result of immunological attack on the bone marrow microenvironment. The relevance of the immune system in this condition is suggested by the following lines of evidence: a) the efficacy of treatment with immune suppressive drugs, which is 60-80% with 5 year survival rates of approximately 75%; b) the presence of immune cell infiltrates in the bone marrow of patients; c) the upregulation of Th1/Th17 cytokines in patients; and d) the presence of abnormally low levels of immune regulatory T cells in patients with aplastic anemia as compared with controls.
Stromal Vascular Fraction (SVF) preparations contain significant numbers of cellular populations with therapeutic activity that would be relevant to aplastic anemia; namely, a) mesenchymal stem cells (MSC), which suppress pathological immune responses and accelerate hematopoiesis; b) endothelial cells, which assist in repairing damaged bone marrow hematopoietic microenvironment and stimulate hematopoiesis; and c) T regulatory cells, which possess anti-inflammatory properties.
Herein we present a trial in progress. We have filed an IND for our study in which we will seek to determine the safety and potential efficacy of intravenously administered autologous SVF cells in 10 patients with severe aplastic anemia that is refractory to immune suppressive therapy. Clinical endpoints will include complete response (CR), defined as a neutrophil count greater than 1.5 × 109/L, a platelet count greater than 150 × 109/L, and a hemoglobin level of greater than 110 g/L (11.0 g/dL). Partial response (PR) is defined by transfusion independence and no longer meeting criteria for severe disease. Relapse is indicated by the requirement for blood transfusion. Toxicity of treatment will be evaluated for the duration of the study and will be graded according to the criteria of the World Health Organization.
Patients will receive an intravenous injection of 100 million autologous SVF collected from 500 cc of adipose tissue on the same day as the liposuction. Patients yielding less than 100 million SVF cells will be excluded. Patients will also receive cyclosporin A 5mg/kg PO for 6 months during the study. Evaluation of bone marrow will be performed pretreatment and at 6 months after treatment, whereas assessment of safety and efficacy will be performed at 1, 3, and 6 months, consisting of blood counts, need for transfusions. Scientific background/rationale for the trial and trial design will be discussed in further depth.
Co-authors
T. Ichim1, A. Patel2, D. Koos1, C. Ichim1.
1Cellular and Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA.
2Director of Cardiovascular Regenerative Medicine, University of Utah, Salt Lake City, USA.
http://mds.kenes.com
$ RGBP $
Oral Presentation 1 Abstract: C.Ichim - TECHNIQUE FOR ESTABLISHMENT OF LONG TERM IN VITRO CULTURES OF PRIMARY MDS CELLS
OR04 Oral Session
MDS Preclinical and mouse models: abstracts
30-Apr-2015 14:00 15:30
Abstract:
TECHNIQUE FOR ESTABLISHMENT OF LONG TERM IN VITRO CULTURES OF PRIMARY MDS CELLS
Myelodysplastic syndrome (MDS) is a bone marrow failure syndrome characterized by peripheral blood cytopenias, apoptosis of bone marrow haematopoietic progenitors, abnormal blood cell morphology (dysplasia) and a marked propensity to progress to acute leukaemia. Basic and pre-clinical research in to the biology of myelodysplastic syndrome is limited by the dearth of suitable cell lines derived from patients with MDS. Many cell lines that have been used in the past to model MDS have been shown to be either cross-contaminated with leukemia cell lines or to be established after MDS transformation in to AML. Methods allowing for the long-term culture of MDS cells are needed.
Herein, we have optimized conditions that have allowed for the maintenance of MDS cells in culture for a period of greater than 4 months by using conditions that minimize differentiation but initiate cycling of long-term repopulating cells. We present cytospins from cells from an MDS patient that had been maintained for 4 months in culture (growing at an exponential rate) using the conditions proposed here. Briefly, progenitor cells and blasts were enriched by negative selection using RosetteSep concurrent with Ficoll-Paque gradient centrifugation.
Mononuclear cells were cultured on a monolayer of irradiated OP9 cells in IMDM medium supplemented with 30ng/mL TPO, 30ng/mL rhIL-11, 30ng/mL rhFlt-3 ligand, 50ng/mL rhG-CSF, 30ng/mL rhGM-CSF, 30ng/mL rh SCF, 10ug/mL insulin, 5ug/mL tranferrin, 0.5% BSA Fraction V, 5% FBS. Finally, cultures were maintained in a nitrogen incubator under hypoxic conditions (2% oxygen). We repeated this protocol with several other patient samples and found the use of fresh bone marrow cells advantageous over viably frozen specimens (2/2 fresh bone marrow samples were able to be cultured in an exponential growth phase for a period that exceeded 4 weeks, whereas 0/4 viably frozen bone marrow samples were able to be cultured in an exponential growth phase for a period that exceeded 4 weeks).
In summary, therapeutic options for patients with MDS are limited. In order to improve efficacy and reduce toxicity of MDS treatment, new therapies must be devised. This is dependent on the availability of suitable preclinical models. Here we report a method of culturing primary cells. We hope that the culture conditions described herein will function to provide the necessary in vitro preclinical models that will accelerate research in the MDS field.
Co-authors
C. Ichim1, D. Koos1, T. Ichim1, R. Wells2.
1Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA.
2Department of Medical Oncology/Hematology Odette Cancer Center, University of Toronto and Sunnybrook Health Sciences Center, Toronto, Canada.
http://mds.kenes.com
$ RGBP $
Oral Presentation 2 Abstract: C.Ichim - NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
OR07 Oral Session
MDS and the aging stem cell: Abstracts
01-May-2015 11:00 12:00
Abstract:
NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
The hierarchical organization of leukemia suggests that discovery of the genes that encode for maintenance of the undifferentiated state of leukemia stem cells will have important clinical relevance. Using a novel single-cell approach that gave unprecedented sample purity, we identified NR2F6 (EAR-2), as a gene associated with leukemia cells that retain the ability to divide. We validated that patients with leukemia and MDS expressed higher levels of NR2F6 mRNA than healthy bone marrow, and showed that silencing of NR2F6 induced differentiation and apoptosis of a human leukemia cell line. Here we studied the roles of NR2F6 in normal hematopoiesis and in the pathogenesis of MDS and acute myelogenous leukemia (AML).
In vitro, primary bone marrow cells engineered to overexpress NR2F6 undergo a block of differentiation, but have greatly extended proliferative ability in colony assays. Overexpression of NR2F6 profoundly impaired differentiation along multiple hematopoietic lineages including the erythroid lineage. NR2F6 over-expressing bone marrow cells formed 40% fewer BFU-E colonies, but had greatly extended replating capacity in colony assays. While knockdown of NR2F6 increased the number of cells produced per BFU-E colony 300%.
In vivo, overexpression of NR2F6 in a chimeric mouse model leads to a condition that resembles MDS 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.
Normal mice transplanted with bone marrow cells from the NR2F6 chimeric mice undergo an expansion of the stem cell compartment in the transplanted mice. This observation was confirmed ex vivo: overexpression of NR2F6 maintained hematopoietic stem cells in culture, while silencing of NR2F6 induces profound differentiation of hematopoietic stem cells. Transplanted animals also developed a rapidly fatal leukemia characterized by pancytopenia, enlargement of the spleen, and infiltration of blasts into the spleen, liver and peripheral blood. Leukemic cells had an erythroblastic morphology and immunophenotype. We further observed an increase of erythroblasts in the bone marrow of preleukemia animals cells, suggesting that over-expression of NR2F6 blocks erythroid differentiation at the erythroblast stage. Mechanistically, we show that DNA binding is necessary for NR2F6 function, and that NR2F6 functions in an HDAC-dependent manner, regulating expression genes involved in erythroid differentiation.
These data establish that NR2F6 is a novel oncogene that controls hematopoietic cell fate decisions and is an ideal target for differentiation therapy of acute leukemia and MDS.
Co-authors
C. Ichim1, D. Dervovic2, D. Koos1, T. Ichim1, R. Wells3.
1Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA.
2Immunology, University of Toronto, Toronto, Canada.
3Department of Medical Oncology/Hematology Odette Cancer Center, University of Toronto and Sunnybrook Health Sciences Center, Toronto, Canada.
http://mds.kenes.com
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Indeed! Two of those are oral presentations, and then one poster presentation on top of those
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You were pretty much dead on with today's news!
Except this is yet ANOTHER conference at the end of this month about Myelodysplastic Syndrome: http://mds.kenes.com/
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NEWS! - Apr 7, 2015 Regen BioPharma Inc. to Present Multiple Presentations at the 13th International Symposium on Myelodysplastic Syndromes
http://www.marketwired.com/press-release/regen-biopharma-inc-present-multiple-presentations-13th-international-symposium-on-myelodysplastic-otcbb-rgbp-2007259.htm
Company Has Two of Its Abstracts Accepted and Upgraded for Oral Presentation, With a Third Abstract Accepted for Poster Presentation on Myelodysplastic Syndrome Related Topics
SAN DIEGO, CA -- (Marketwired) -- 04/07/15 -- Regen BioPharma Inc. (OTCBB: RGBP) (OTC PINK: RGBP) announced today that the 13th International Symposium on Myelodysplastic Syndromes has accepted three presentations prepared by Regen BioPharma Inc. The accepted abstracts highlight the work being done in the Company's area of expertise in Aplastic Anemia and Myelodysplastic Syndrome. The link to the conference is http://mds.kenes.com
Myelodysplastic Syndrome is a disease of bone marrow failure, where blood cells fail to form because bone marrow stem cells fail to differentiate. The Company has filed one IND in this space on HemaXellerate treatment for aplastic anemia and is working on preclinical development of DiffronC, an siRNA based therapeutic targeting cancer stem cell genes involved in blood cell differentiation.
The three presentations are:
-HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA
-NR2F6 (EAR-2) IS A NOVEL LEUKEMIA AND MDS ONCOGENE, OVER-EXPRESSED IN PATIENTS, THAT INHIBITS HEMATOPOIETIC DIFFERENTIATION AND BLOCKS ERYTHROPOIETIC DIFFERENTIATION AT THE PROERYTHROCYTE STAGE
-TECHNIQUE FOR ESTABLISHMENT OF LONG TERM IN VITRO CULTURES OF PRIMARY MDS CELLS
Regen's Chairman & CEO David Koos stated, "These three presentations represent an exciting turning point for the Company. We are gaining credibility and exposure in our fields of research among the top biotechnology scientists around the world. This should lead to potential collaborations that aid in our future progress."
ABOUT REGEN BIOPHARMA INC.: Regen BioPharma Inc. is a publicly traded biotechnology company (OTCBB: RGBP) and (OTC PINK: RGBP). The Company seeks to identify undervalued regenerative medicine applications in the immunotherapy and stem cell space. The Company is focused on rapidly advancing these technologies through pre-clinical and Phase I/ II clinical trials. Currently the Company is centering on gene silencing therapy for treating cancer, telomeres and small molecule therapies, along with developing stem cell treatments for aplastic anemia.
Disclaimer: This news release 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, PhD
Chairman & Chief Executive Officer
619-702-1404 Phone
619-330-2328 Fax
www.regenbiopharma.com
Right on, nice to see them building the IP and protecting themselves before further development. They've really been pushing this project lately; I'm thinking because of C.Ichim's determination to see it through to clinical applications and large collection of development work. No doubt they are positioning this for a solid IND - can't wait to see that happen.
Also, I agree CV, I'd guess we'll see that PR after the Cold Spring Harbor Conference (April 8-11) and before the AACR conference in Chicago (April 18-22) to announce that one as well.
Happy Easter Monday everyone!
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Thanks for sharing this Mando! This abstract definitely helps understand the strong foundation of this work and where it is currently. The following line makes me think they still have some work to do before this becomes an IND, but it will be very interesting when it does:
"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."
Thanks, not necessary for the point I was trying to make though, that's all close enough. I was just poking fun at how a concrete fact like the correct O/S is not an "opinion" :-P
"In Your Opinion"? or it actually is over 4B? lol
Either way, that'd bring the calculated expected BMSN PPS to 0.0015
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Based on their 30M shares of RGBP alone, BMSN should at least have a market cap of $6M, and therefore a PPS of 0.0016 * Instead, we're only seeing about 1/3 of that.
*calculated using an RGBP PPS of 0.20 and a BMSN O/S of 3.73B
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I just wanted to expand on your comment, CV, and add some background DD surrounding the HemaXellerate safety studies.
Back in July 2013, BMSN shared some efficacy data for HemaXellerate, which monitored white blood cell count over 14 days after bone marrow injury.
Based on experiments that FDA requested, the company generated new data further demonstrating efficacy of HemaXellerate I™ in animal models. This may be seen in the figure attached.
Efficacy Figure: http://www2.marketwire.com/mw/frame_mw?attachid=2370423
Link to the source PR: http://ih.advfn.com/p.php?pid=nmona&article=58628844
IMO it's better to have this problem than have no PRs and be left in the dark for weeks/months at a time like we were before. I think it's only a matter of time before the PPS catches up to these advancements. As has been said before, some strong FDA approval news will be needed to validate all the other smaller events we've seen.
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Here's the conference website with Christine Ichim's poster listed. Scroll down to find "Ichim, C.V.":
http://meetings.cshl.edu/abstracts/rnatx2015_absstat.html
Development of DiffronC gene silencing technology for silencing of the novel leukemia stem cell target NR2F6
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Today makes 7 Tuesday Koosday Newsdays in a row
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Nice catch CV! That was going to be my next step; looking up these doctors' backgrounds. I'll be interested to hear if any of these new Advisory Board members are being utilized to provide connections to a good GLP lab or people to conduct the eventual clinical trials.
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