SEC Company Response from Regen BioPharma Inc (RGBP, RGBPP) (CIK 0001589150) (RGBP) — Jan 29, 2014
Regen BioPharma Inc (RGBP, RGBPP) (CIK 0001589150)
Date: Jan. 29, 2014 · CIK: 0001589150 · Accession: 0001554795-14-000060
AI Filing Summary & Sentiment
File numbers found in text: 333-191725
Referenced dates: December 5, 2013
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CORRESP
1
filename1.htm
January 10, 2014
United States Securities and Exchange Commission
Division of Corporation Finance
100 F Street, NE
Washington, DC 20549
Attention: Suzanne Hayes, Assistant Director
Michael Seaman
Celia Soehner
Re: Regen Biopharma, Inc.
Registration Statement on Form S-1
File No. 333-191725
Amended November 22, 2013
Dear Ms. Hayes, Mr. Seaman and Ms. Soehner:
The following responses address the comments of the Staff (the “Staff”)
as set forth in its letter dated December 5, 2013 (the “Comment Letter”) relating to the Registration Statement
on Form S-1/A of Regen Biopharma, Inc. (The "Company").
1. The following revisions have been made:
Regarding the term autologous on page 3 of the S-1/A:
“On February 5, 2013 Regen filed an Investigational
New Drug (IND) application with the United States Food and Drug Administration to initiate a clinical trial. In this study 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 resistant to immune suppressive therapy.”
Has been amended to read:
“On February 5, 2013 Regen filed
an Investigational New Drug (IND) application with the United States Food and Drug Administration to initiate a clinical trial.
In this study we will seek to determine the safety and potential efficacy of intravenously administered autologous (derived or
transferred from the same individual's body) SVF cells in 10 patients with severe aplastic anemia that is resistant to immune suppressive
therapy. “
Regarding the term indoleamine 2,3-dioxygenase
on page 4 of the S-1/A:
indoleamine 2,3-dioxygenase is defined in this paragraph
as IDO
“dCellVax is intended to be a
therapy whereby dendritic cells of the cancer patient are harvested from the body , treated with plasmid DNA that has the ability
to block the dendritic cell from expressing indoleamine 2,3-dioxygenase (“IDO”) and subsequently reimplanted in the
cancer patient. A plasmid is a small DNA molecule that is physically separate from, and can replicate independently of, chromosomal
DNA within a cell. “
IDO is further elaborated upon in the
following paragraph:
“IDO is an enzyme that is believed
to suppress the body’s immune response to the cancer cells by suppressing T Cells as well as halting the dendritic cell from
activating T cells. The dendritic cells that are treated with the IDO-blocking plasmid become resistant to the influence of cancer
cells which cause the dendritic cell to express IDO. “
The following sentence has been added
to the abovementioned paragraph:
“T cells are a type of lymphocyte
(itself a type of white blood cell) that play a vital role in the body’s immune response.”
Regarding defining at the time of first
use the acronym IND on page five. The fist Use of the acronym IND is on page three where it is defined as “an Investigational
New Drug (IND) application” within the sentence:
“On February 5, 2013 Regen filed
an Investigational New Drug (IND) application with the United States Food and Drug Administration to initiate a clinical trial. “
Regarding the use of the term “drug –refractory”
on page 12:
“NO APPROVAL HAS BEEN GRANTED BY THE FDA FOR
THE MARKETING AND SALE OF HEMAXELLERATE
On February 5, 2013 Regen filed an Investigational New
Drug (IND) application with the United States Food and Drug Administration to initiate clinical trials assessing the Company’s
HemaXellerate drug currently in development in patients with drug-refractory aplastic anemia. Regen will be required to obtain
approval from the US Food and Drug Administration (FDA) in order to market HemaXellerate. No approval has been granted by the FDA
for the marketing and sale of HemaXellerate.”
Has been amended to read:
“NO APPROVAL HAS BEEN GRANTED BY THE FDA FOR
THE MARKETING AND SALE OF HEMAXELLERATE
On February 5, 2013 Regen filed an Investigational New
Drug (IND) application with the United States Food and Drug Administration to initiate clinical trials assessing the Company’s
HemaXellerate drug currently in development in patients with drug-refractory aplastic anemia. A condition is classified as drug-refractory
if the patient is unresponsive to drug therapy. Regen will be required to obtain approval from the US Food and Drug Administration
(FDA) in order to market HemaXellerate. No approval has been granted by the FDA for the marketing and sale of HemaXellerate.”
Regarding a lack of a definition for “short interfering
RNA” on page 18
The phrase:
“On May 1, 2013 Dr. Wei Ping Min (“Min”)
entered into an agreement (“Agreement”) whereby Min assigned to Regen all right, title and interest in US Patent #
8,389,708 as well as all Patent applications from the same family corresponding to numbers PCT/CA2006/000984, CA2612200 and EP1898936.(“Min
IP”) US Patent # 8,389,708 was granted to Min with regard to his invention of a method directed to the silencing of immunosuppressive
cancer causing genes using short interfering RNA (siRNA) leading to an increase in the immune response, a decrease in tumor-induced
immunosuppression and a decrease in in vivo tumor progression”
Has been amended to read
“On May 1, 2013 Dr. Wei Ping Min (“Min”)
entered into an agreement (“Agreement”) whereby Min assigned to Regen all right, title and interest in US Patent #
8,389,708 as well as all Patent applications from the same family corresponding to numbers PCT/CA2006/000984, CA2612200 and EP1898936.(“Min
IP”) US Patent # 8,389,708 was granted to Min with regard to his invention of a method directed to the silencing of immunosuppressive
cancer causing genes using short interfering RNA (siRNA) leading to an increase in the immune response, a decrease in tumor-induced
immunosuppression and a decrease in in vivo tumor progression. siRNA are shorter pieces of double stranded RNA that allow
the interference of a particular gene, without causing cell death.”
Regarding the penultimate paragraph of the Business
section on page 20 including references to mesenchymal stem cells and endothelial cells:
The paragraph:
“The Company has begun development of
HemaXellerate I , a cellular therapy designed to heal damaged bone marrow. HemaXellerate I is a patient-specific composition of
cells that have been demonstrated to repair damaged bone marrow and stimulate production of blood cells based on previous animal
studies. The initial application of HemaXellerate I will be the treatment of severe aplastic anemia which is characterized by immune-mediated
bone marrow hypoplasia (underdevelopment or incomplete development of a tissue) and pancytopenia( reduction in the number of blood
cells and platelets).
Adipose tissue is collected from the patient
and processed in order to separate , extract and isolate Stromal Vascular Fraction (SVF), a mix of various cell types including
mesenchymal stem cells and endothelial cells. The isolated SVF is then intravenously administered to the patient. The Company believes
that the isolated SVF will generate growth factors with the ability to repair damaged hematopoietic stem cells. Hematopoietic stem
cells are immature cells that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets.
Hematopoietic stem cells are found in the peripheral blood and the bone marrow.”
Has been revised as follows:
“The Company has begun development of
HemaXellerate I , a cellular therapy designed to heal damaged bone marrow. HemaXellerate I is a patient-specific composition of
cells that have been demonstrated to repair damaged bone marrow and stimulate production of blood cells based on previous animal
studies. The initial application of HemaXellerate I will be the treatment of severe aplastic anemia which is characterized by immune-mediated
bone marrow hypoplasia (underdevelopment or incomplete development of a tissue) and pancytopenia( reduction in the number of blood
cells and platelets).
Adipose tissue is collected from the patient
and processed in order to separate , extract and isolate Stromal Vascular Fraction (SVF), a mix of various cell types including
mesenchymal stem cells and endothelial cells. Mesenchymal stem cells are connective tissue cells that can differentiate into a
variety of cell types and endothelial cells are the cells that line the interior surface of blood vessels and lymphatic vessels
and which play a vital role in angiogenesis ( the physiological process through which new blood vessels form from pre-existing
vessels).
The isolated SVF is then intravenously administered
to the patient. The Company believes that the isolated SVF will generate growth factors with the ability to repair damaged hematopoietic
stem cells. Hematopoietic stem cells are immature cells that can develop into all types of blood cells, including white blood cells,
red blood cells, and platelets. Hematopoietic stem cells are found in the peripheral blood and the bone marrow.”
With regards to descriptions of preclinical data on
page 21
Laboratory Experiments
Experiment
Location Conducted
Dates Conducted
Number of Animals/Runs
Preclinical Data
Demonstration that endothelial cells stimulate hematopoiesis after bone marrow damage
Dr. William Fleming, Oregon Health Sciences University
2008-2009
37 C57/B6 mice exposed to lethal irradiation and treated with increasing numbers of endothelial cells
Demonstration of radioprotection by endothelial cells, associated with augmentation of hematopoiesis. Data in patent and also part published in Lei et al. Stem Cell Res. 4(1): 17–24
Optimization of Human SVF Isolation and Characterization
Dr. Erik Woods, Cook General Biotechnology
June 2012- August 2012
5 human samples of fat processed under various conditions to optimize content of endothelial cells
Protocol developed for optimal content of endothelial cells from human fat, as detected by flow cytometry
Development of irradiation model of myeloablation in immune compromised mice
Dr. Sophia Khaldoyanidi
Torrey Pines Institute for Molecular Studies
Aug-Nov 2012
50 C57/B6 and SCID mice treated with various doses of irradiation and administered bone marrow cells as a source of endothelial cells
Development of a model of bone marrow failure, practical issues learned about bone marrow as a source of endothelial cells, decision to focus on use of adipose tissue as source instead of bone marrow
Human HemaXellerate Efficacy in Mouse Model
Dr. Wei-Ping Min, University of Western Ontario
Jan-April 2013
40 mice treated bone marrow toxin, followed by administration of 3 doses of HemaXellerate or control
Dose dependent demonstration of accelerated hematopoiesis after administration of HemaXellerate
21
Preclinical studies conducted by the Company consist
of the following:
1.
Development of HemaXellerate product. Studies were conducted together with Cook Biotechnology for the establishment of protocols for manufacturing a consistent cellular product based on enzymatic digestion of patient fat tissue, centrifugation, and washing steps.
2.
Development of Animal model. Sophia Khaldoyanidi, M.D., Ph.D. at the Torrey Pines Institute for Molecular Medicine to established the animal model for aplastic anemia and assessed feasibility of endothelial stem cell stimulation of blood cell production.
3.
Preclinical Demonstration of Efficacy. Data was generated using the model developed from work with Dr. Khaldoyanidi to demonstrate a dose dependent effect of HemaXellerate I on stimulation of new blood cell formation. The study demonstrated accelerated reconstitution of white blood cells production after administration of 5-FU ( a chemical that kills bone marrow stem cells) after HemaXellerate therapy which in the opinion of the Company demonstrates efficacy of HemaXellerate and the cellar components of SVF
References showing that endothelial cells and endothelial
progenitor cells, which comprise 16% of SVF (Zimmerlin et al. Cytometry Part A 77A: 22:30, 2010) produce growth factors that stimulate
blood cell production from bone marrow support the Company’s position that isolated SVF will generate growth factors with
the ability to repair damaged hematopoietic stem “
Has been amended to read as follows:
“In the opinion of the Company, the following studies
conducted by or on behalf of the Company or by others demonstrate that the composition of cells in HemaXellerate
I have been demonstrated to repair damaged bone marrow and stimulate production of blood cells .
Laboratory Experiments
Experiment
Location Conducted
Dates Conducted
Number of Animals/Runs
Preclinical Data
Demonstration that endothelial cells stimulate hematopoiesis after bone marrow damage
Dr. William Fleming, Oregon Health Sciences University
2008-2009
37 C57/B6 mice exposed to lethal irradiation and treated with increasing numbers of endothelial cells*
Demonstration of radioprotection by endothelial cells, associated with augmentation of hematopoiesis. Data in patent and also part published in Lei et al. Stem Cell Res. 4(1): 17–24
Optimization of Human SVF Isolation and Characterization
Dr. Erik Woods, Cook General Biotechnology
June 2012- August 2012
5 human samples of fat processed under various conditions to optimize content of endothelial cells
Protocol developed for optimal content of endothelial cells from human fat, as detected by flow cytometry
Development of irradiation model of myeloablation in immune compromised mice
Dr. Sophia Khaldoyanidi
Torrey Pines Institute for Molecular Studies
Aug-Nov 2012
50 C57/B6 and SCID mice treated with various doses of irradiation and administered bone marrow cells as a source of endothelial cells*
Development of a model of bone marrow failure, practical issues learned about bone marrow as a source of endothelial cells, decision to focus on use of adipose tissue as source instead of bone marrow
Human HemaXellerate Efficacy in Mouse Model
Dr. Wei-Ping Min, University of Western Ontario
Jan-April 2013
40 mice treated bone marrow toxin, followed by administration of 3 doses of HemaXellerate or control
Dose dependent demonstration of accelerated hematopoiesis after administration of HemaXellerate
*“50 C57/B6”
is the label of a type of mouse commonly used in research. It is a mouse that possess a functional immune system. In the first
experiment described in the table, the mice were treated with a lethal dose of radiation. Radiation kills by destroying the blood
making cells of the body. Administration of mouse derived endothelial cells resulted in enhanced survival of the mice after irradiation,
which was associated with restoration of blood production. These sets of experiments strongly suggested to us, that endothelial
cells protect blood making cells from damage. SCID (severe combined immuno deficient) mice are commonly used in research where
a human cell therapeutic product is being tested in a manner to avoid rejection of the cells by the mouse’s immune system.
In this segment of the research, human cells were given to the SCID mice subsequent to irradiation, which regenerated the mouse
blood making cells. The purpose of the 50 C57/B6 mice and the SCID mice in the research is to demonstrate that mouse derived endothelial
cells regenerate blood making cells and that human endothelial cells regenerate blood making cells in mice.
Preclinical studies conducted by the Company consist
of the following:
1. Development of HemaXellerate product. Studies were conducted together with Cook Biotechnology
for the establishment of protocols for manufacturing a consistent cellular product based on enzymatic digestion of patient fat
tissue, centrifugation, and washing steps.
2. Development of Animal model. Sophia Khaldoya