Investing in
Regenerative
Medicine:
Technology
Analysis and
Market Outlook
2014 Report #1
ISBN # 978-0-9912902-1-5
May 2014
Glossary
2
Table of
Introduction
4
Contents
Regenerative Medicine Landscape
5
Industry Segmentation
7
Highlights of 2013
33
Collaborations, Partnerships, & Alliances
34
Launching New Projects, Products, & Services
37
Accomplishments
40
Capital Market Deals
41
Industry Landscape
42
Chart 1: Company Locations....................................................................................43
Chart 2: Organization Types
44
Chart 3: Products for Specific Conditions
44
Chart 4: Supply Lines
45
Chart 5: Company Specialties, 1971-2012
45
Chart 6: Product Trends
46
Chart 7: Company Interests
47
Chart 8: Market Cap
48
Deals and Partnerships
48
Number of Partnership Deals Announced
49
Partnerships by Therapy Area
50
Trends
51
Growing Stem Cell Research..................................................................................52
Point-Of-Care Cell Therapy
55
3D-Bioprinting
55
Why Should “Big Pharma” Be Interested?
58
Medical Tourism
58
Clinical Trials
60
Cell Therapy Clinical Trials
61
Tissue Engineering Clinical Trials
65
Platelet-Rich Plasma Clinical Trials................................................................... 69
Gene Therapy Clinical Trials
71
Companies And Products Acting In Gene Therapy
74
Results of Clinical Trials
75
Market approvals
81
FDA Approvals
81
European Medicines Agency Approvals
82
Notable Public Companies
83
REFERENCES
101
1
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Glossary
3D-bioprinting: layer-by-layer approach to
Embryonic stem cells (ES cells): pluripotent
create tissue and organ architecture using bio-
stem cells derived from an early-stage embryo.
ink and structure materials.
Implant: non-biological medical device
Bio-ink: multicellular building blocks for
designed to improve or replace a biological
bioprinting.
structure.
Adult stem cells: multipotent stem cells that
Expression: realization of information from a
can be found in juvenile and adult organism.
gene within the cell.
Allogeneic: taken from the same species but
Extracellular matrix: tissue material between
genetically different.
cells.
Autologous: taken from the same organism.
Ex vivo: outside the living organism.
Biomaterial: biocompatible material interacting
In silico: performed on a computer or via
with the body to improve biological functions
computer simulation.
and replace faulty cellular structures.
In vitro: performed in laboratory conditions
Cells: basic structural, functional and biological
rather than within a living organism.
unit of all living organisms except viruses.
In vivo: within the living organism.
Cell therapy: administration of cells into the
Induced pluripotent stem cells
body in order to treat a disease or improve the
(iPSC or iPS cells): pluripotent stem cells
function of the existing cells.
derived from non-pluripotent cells by
Clinical trial: stage of medical research that
reprogramming of genes.
gives information of safety and efficacy for
Isogenic: taken from another organism but
health interventions in humans (drugs, therapy
genetically identical.
protocols, diagnostics etc.).
Gene therapy: introduction of genetic material
Phase 0 trial: first in-human trials in small
into cells to treat a disease.
groups of patients to investigate the response
of a new intervention in humans (e.g. drug
Genetic vector: DNA or RNA molecule used
pharmacodynamics and pharmacokinetics).
for the introduction of foreign genetic material
into the cells for research or medical treatment.
Phase 1 trial: trials in a small group of patients
to screen the method of intervention for safety.
Medical Tourism: the practice of a patient
traveling from one country to another to receive
Phase 2 trial: experimental treatment of larger
medical treatment that is not available or not
groups of people to investigate the safety and
approved in their country of origin.
effectiveness of new intervention against a
placebo.
Multipotent stem cells: stem cells that can
Phase 3 trial: final confirmation of the safety
differentiate into a family of related cells.
and efficacy for a new intervention.
Oligopotent stem cells: stem cells that can
Phase 4 trial: post-marketing studies of the
differentiate into a few cell types.
risks and benefits of the new intervention as
well as the determination of optimal usage for
Plasmid vector: small circular double-stranded
the intervention.
bacterial DNA that can replicate independently
within of the chromosomal DNA in a cell.
2
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Glossary (cont’d.)
Pluripotent stem cells: stem cells that can
Transplant: biological material placed into
differentiate into all cells except embryonic
recipient organism to improve or replace a
cells.
biological structure.
Regenerative medicine: field of medicine
Viral vector: genetically engineered viruses
referring to approaches for replacing or
carrying noninfectious modified viral DNA or
regenerating human cells, tissues or organs to
RNA.
improve or restore biological functions.
Retroviral vector: RNA-containing viral vectors
Reprogramming: deriving less differentiated
that can integrate only into the genome of
cells from more differentiated ones by forced
dividing cells.
expression of specific genes.
Lentiviral vector: RNA-containing viral vectors
Scaffold: artificial structure capable of
that can integrate into genome of non-dividing
supporting the formation of a three-
and dividing cells.
dimensional tissue.
Adenoviral vector: DNA-containing viral vector
Stem cells: undifferentiated biological cells
that does not integrate into the genome and
that have ability for self-renewal and a capacity
does not replicate during cell division.
to differentiate into specialized cell types.
Xenogenic: originating from foreign substance.
Tissue: group of similar cells from the same
origin that together carry out specific function
in the body.
Totipotent stem cells: stem cells that can
differentiate into all embryonic and extra
embryonic cell types.
Tissue engineering: use of cells, engineering,
materials, factors and methods to manufacture
tissues and organs ex vivo in order to improve
or replace biological functions.
Transcription: copying of DNA into RNA by the
enzyme RNA polymerase.
Transcription factor: protein that specifically
binds to a known DNA sequence in the gene
and controls the transcription of genes.
Translation: The process of protein synthesis
by ribosomes, using the code from the RNA
sequence within the cell.
3
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
and diseases. ARMIF highlights the focus on
the level of organismal organization such as
Introduction
cells, tissue, and organs.
The field of regenerative medicine
The presence of an individual company and
encompasses many areas of scientific
that company’s level of activity in each market
research and clinical applications. While
segment is visualized using color codes for
many attempts have been made to compare
low, medium, and high.
various companies, research organizations,
For example, if the company’s main
and research projects, few models account for
business is supplying reagents and cells, the
the whole industry supply chain and the fact
appropriate segments are highlighted in red.
that many companies participate in multiple
If the company is engaged in research of
industry segments.
multiple cell types, but is mostly focusing on
For example, some of the companies supply
autologous cells, but it also has projects using
reagents, equipment, and cells and may
allogeneic cells and is just starting the induced
have a conservative growth projection, being
stem cell program, each one of these fields
less risky from the cash flow and clinical
will be color coded by the company’s level of
trials perspectives, and may also have basic
activity in each field.
research or translational medicine projects that
To facilitate an effective analysis and
may serve as major sources of growth.
comparison of the companies and projects
Likewise, companies engaged in “high risk
in regenerative medicine, we created an
/ high reward” projects that are not publicly
advanced knowledge management system
known may have research divisions working
called AgingAnalytics.com.
on novel research projects that may be out-
The system tracks over 150 public and private
licensed to other industry participants and
companies engaged in the regenerative
provide stable sources of funding.
medicine industry and uses the ARMIF
There are a vast number of biotechnology
model to analyze and compare these
companies and healthcare organizations which
companies. In addition to the color codes,
are not classically classified as players in the
the AgingAnalytics system allows for each
regenerative medicine field, but are either
segment to be evaluated using multiple
providing services to the industry acting as
parameters of competition, growth, growth
suppliers or deploying regenerative medicine
potential, technology risk, legal risk, and other
technologies in the clinic, thereby contributing
factors. These parameters can then be used to
to the creation of demand.
evaluate and compare industry segments and
companies, along with clinical and research
Some of the large biopharmaceutical
organizations, as well as specific projects.
companies often have research or translational
medicine divisions that occupy leadership
While ARMIF is currently limited in both
positions in certain industry segments. These
granularity and scale, it is one of the most
divisions are insignificant compared to the rest
of the company, but have leadership positions
in certain industry segments.
To address these issues, we developed a
comprehensive Analytical Regenerative
Medicine Industry Framework (ARMIF),
which incorporates many segments of the
regenerative medicine industry and includes
services, enabling technologies, technologies
Sample ARMIF diagram. Refer to page 85 for full page diagrams and
industry segment analyis.
for manipulation at the cellular and tissue level,
4
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
comprehensive models for analyzing the
This table can also be used for the description
organizations and projects in the field of
of the companies working in regenerative
regenerative medicine. The system not only
medicine. Each company’s table has its own
allows us to analyze a company’s positioning,
representation of its presence and activities in
but also to evaluate the company’s level of
the industry. If a company develops a particular
industry participation and to track multiple
technology or provides a particular service,
parameters in each market or research
the respective table cell will be marked with a
segment.
color code. Otherwise, it will remain white.
It is a scalable and flexible platform that
The first two levels in this table are
allows for new parameters to be added as the
represented as ‘Services’ and ‘Enabling
industry develops to produce new innovations
technologies.’ Services form a vital part of any
and new applications.
industry, and Enabling technologies provide
an innovative thrust for future developments in
the field of regenerative medicine.
The next four levels in the table are very similar
to the levels of the biological organization in
humans.
Molecular induction technologies are a very
important part of regenerative medicine. The
molecular level of the organization of the body
Regenerative
is the simplest one, but it is not less important
than the others.
Medicine
The cellular level of the organization in
the body has a higher complexity than the
Landscape
molecular level. Cells form the traditional
basis of regenerative medicine, as they are
Viewed comprehensively, the Regenerative
the primary unit involved in the regenerative
Medicine industry includes a diverse range
process. A large number of current treatment
of suppliers, specialist contract research
modalities in the field of regenerative medicine
organisations and hospitals. The makeup of
are based on cells or cell-derived products.
the industry includes not only the primary
The organization at a tissue level is strongly
companies involved directly in the regenerative
connected to the cellular level. The source
medicine business, but also the services
of cells and tissues can be classified into
industry. Also associated are diverse fields like
four different groups based on the source
bioengineering, the chemical industry, and the
of the cell/tissue material and the cells’
pharmaceutical industry, as well as clinics and
immunogenic capacity:
hospitals involved in trials.
1.
Autologous: Cells and/or tissues derived
We have developed a map which can help
from the same person who is undergoing
one to understand the regenerative medicine
a treatment. Autologous cells/tissues have
industry landscape. The projection of this map
a very low probability of rejection after
is in the form of a table, which is divided into
transplantation.
several levels (horizontal rows). Each level in
this table represents a separate part of the
2. Allogeneic: Cells and/or tissues derived
regenerative medicine industry, but some of
from a person, for the treatment of
these levels are strongly connected. There
another person. Allogeneic cells/tissues
may be some segments in a level which
have a large probability of rejection after
describe specific technologies or services.
transplantation.
5
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
3. Isogenic: Cells and/or tissues derived from
in turn are composed of different cell types.
a person with the same genetic make-up
Bio-engineered organs have already been
as the patient (for example, from a twin).
produced, and some of them have already
Isogenic cells and tissues also have a
been successfully transplanted.
rather low probability of rejection after
And the final level is the level of diseases,
transplantation.
where some particular treatments are
4. Xenogenic: Cells and/or tissues derived
discussed.
from an animal and intended for the
Every table cell is described in the next
treatment of a person. Xenogenic cells and
chapter, which is called Segmentation.
tissues have a large probability of rejection
after transplantation.
The next level of complexity in an organism
is organization on the organ level. Each organ
consists of different types of tissues, which
6
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Industry Segmentation
7
Blood
Immunological
Gastrointestinal
Reproductive System
Cancer
Wounds
Diseases
Diseases
Diseases
Diseases
Cardiovascular
Neurological
Ocular
Urinary System
Muscular and Skeletal
Diabetes
Diseases
Diseases
Diseases
Diseases
Disorders and Injuries
Cardiovascular
Bones and
Kidney
Liver
Bladder
Skin
Pancreas
Trachea
Teeth
System
Cartilages
With Scaffold
Without Scaffold
Autologous
Allogeneic
Isogenic
Xenogenic
Connective
Muscle
Epithelial
Nervous
Autologous
Allogeneic
Isogenic
Xenogenic
Embryonic Stem Cells (ES)
iPSC
Adult Stem Cells
Artificial Cells
Small molecules and
Genetic Therapy (vectors)
Combination
proteins
Reagents and
Cell and Tissue
Information
Equipment
Implants
Materials
Sources
Systems
Contract Research
Contract
Clinics /
Aesthetic
Consulting / Legal
Biobanks
Clinical Trials
Organization
Manufacturing
Hospitals
Medicine
Certification
(CRO)
(CM)
Table 1 : Segmentation of the Regenerative Medicine Industry
collected, processed, and stored. The bio-
Segment 1.
specimens can be used for different purposes
such as scientific research and transplantation.
Services
In this section, we shall cover biobanks which
Services form an important part of any
are focused on storage of different cells and
industry. In the field of regenerative medicine,
tissues for future transplantation, as they are
their role can hardly be overstated because
of significant relevance in the regenerative
it is a new area, and all stakeholders face
medicine industry.
pressure from the industry. A well-organized
Present day technology makes it possible
services sector supporting the regenerative
to collect a large number of different cell
medicine industry can undoubtedly make a
and tissue types from the human body. For
great contribution to the development of the
example, collected material can be adipose
field. Some of the associated service providers
tissue, cord blood, amniotic stem cells and
cater to the needs of companies, while others
skin, and so on.
provide services to the final consumers.
Biobanks can be publicly or privately
A. Biobanks
controlled. Public banks collect cells and
A biobank is a repository of different biological
tissues and make them available for anyone
materials such as blood, umbilical cords,
who needs a transplantation. In such cases,
cells, and tissues, where these materials are
donors are not assured that their donated
8
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Chart 1:
Funding received by
Biobanks.
specimens will be available to them in future,
that small scale companies engaged in the
such as in the case of a donor contracting
development of therapeutics prefer to use the
a disease. Public banks are non-profit
services provided by companies specialized in
organizations.
getting approvals for and conducting clinical
trials. One example is multinational Contract
Private biobanks are commercial organizations
Research Organization PAREXEL, with a
which offer their clients a possibility to store
corporate presence across several continents.
their tissues and cells for potential use in the
According to Yahoo Finance, this company’s
future at a cost.
market cap is currently about 2.84 billion
dollars.
Cord blood banks are an example of the most
successful biobanks. According to the Alliance
Such specialized companies provide services
for Regenerative Medicine (URL Ref. 1), More
that can be helpful for the development of
than 30,000 cord blood transplants have been
the regenerative medicine field, as a large
performed leading up to the year 2012. The
number of small companies, incapable of
popularity of private cord blood banks is rising
conducting such trials independently, can use
sharply, but there is a strong opinion that the
the expertise and know-how of the companies
average probability of usage of the transplant
engaged primarily in clinical trial development.
material by its donor is too low, giving an
FundingTrends.org cites that the funding
advantage to the public banks in terms of the
of clinical trials related to the regenerative
potential for developing research and real-
medicine field has sharply increased since
world transplant studies.
2003,
According to FundingTrends.org, funding of
Contract Research Organizations (CROs)
biobanks has risen sharply since the year 2003,
and reached a plateau in 2009.
A Contract Research Organization is an
organization which provides different
B. Clinical trials
research services to the pharmaceutical and
biotechnological companies on a contract
Clinical trials are an extremely important, but
basis. For example, services provided can
cost- and time-intensive step towards bringing
come in the form of biological assays,
a research product to the market once its
preclinical trials, etc.
safety and efficacy can be evaluated. The
process of conducting clinical trials can face
These CROs have a strong connection with
many challenges, and this is the precise reason
the regenerative medicine field. Firstly, their
9
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Chart 2: Funding
for clinical trials in
regenerative medicine.
services can be very helpful for the companies
stakeholders in the regenerative medicine
which are focused on development of a
industry. In any case, all clinical trials and fully
particular regenerative technology. Secondly,
developed therapies are connected with
these CROs are often the first clients to test
eventual clinical and medical applications.
new models developed by the regenerative
These institutions can also participate in
medicine industry, one example being the new
the development of different regenerative
3D tissue models that are gaining popularity in
technologies, as they have their own research
the field of drug testing.
facilities and real world data to collect.
The annual growth of the CRO segment of the
In the future, the role of clinics shall be
market in the United States is 12.1 % and annual
increasingly important as it is often easier
revenue is about $15 billion (URL Ref. 2).
to produce stem cell products onsite in a
hospital rather than in a separate laboratory.
C. Contract Manufacturing (CM)
The delivery of any stem cell product is a
complex process involving considerable
A Contract Manufacturer is an organization
regulation. Moreover, some products have
which manufactures a product on a
to be used immediately after preparation,
contract basis. Of the diverse assortment
as they have a short shelf life and may be
of manufacturers across the biomedical
subjected to damage upon storage and/or
industry, some contract manufacturers provide
transportation. Hospitals and clinics can be a
specialized manufacturing services for the
valuable source of the donor material and at
regenerative medicine industry. Again, as
the same time provide the most appropriate
mentioned in the case of CROs, CM can be
facilities to deliver the product to the recipient.
beneficial for small innovative companies
Hence, in the future, big hospitals and clinics
which may have a breakthrough product but
are expected to play major roles in the field of
do not have the manufacturing capabilities.
regenerative medicine.
The list of products which can be produced
by such organizations is rather extensive. It
E. Aesthetic Medicine
includes different reagents, vectors for gene
therapy, induced pluripotent stem cells, and
The technologies of regenerative medicine
the list goes on.
can make a serious contribution to aesthetic
medicine. Regeneration and protection of
D. Clinics and Hospitals
the skin is one of the most important aims of
cosmetic procedures. Several technologies
Clinics and hospitals are considerable
10
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
which are currently used for the treatment of
work area, which is necessary for the process
connective tissue and skin related problems
of carrying out manipulations with cells and
are also relevant for cosmetic purposes. For
tissues. Incubators are needed for maintaining
example, the company Anika Therapeutics
special conditions (gas composition,
manufactures and markets products which can
temperature, etc.) for proper cell growth.
be used for correction of facial wrinkles, scar
Moreover, some incubators contain special
remediation, and lip augmentation (URL Ref. 3).
microscopes which allow real time imaging of
cell development and to correct it when it is
F. Consulting and Legal Certification
needed.
(URL Ref. 4)
Consulting and legal certification is an
extremely important part of the services
Refrigerators are used for storage of some
sector benefitting regenerative medicine.
reagents. Freezers can be used for different
The rules and regulations covering products
purposes. There are three types of them
and services in regenerative medicine differ
(-20°C, -80°C, and liquid nitrogen freezers
between national jurisdictions. Moreover, the
with the temperature of -196°C). The first two
regulations are often not easy to interpret, and
are primarily used for storage of reagents,
the innovator often requires professional legal
but the third is used for the preservation of
and regulatory personnel to get through the
biomaterials (cells, tissues, etc.).
process of legal certifications and regulatory
boards.
Other equipment (centrifuges, shakers,
pipettes, etc.) is used for different
Consulting and analytics are also important,
manipulations with cells and tissues.
as regenerative medicine is a very dynamic
industry and stakeholders need to keep
B. Reagents and Materials
apprised of industry events to inform decision-
Another segment of enabling technologies
making.
is the production of different reagents and
materials. The reagents used in regenerative
medicine are varied and diverse. The list
Segment 2.
includes cell culture media, different solutions,
growth factors, cytokines, antibodies, and
Enabling
other chemical compounds. Companies such
Technologies
as Life Technologies Corporation, STEMCELL
Technologies, Inc., and others provide a wide
range of such reagents.
Enabling Technology, as the name suggests,
is a driving innovation or technology that
Another important part of the market is
can radically change existing capabilities, to
production of different biomaterials. These
the benefit of service providers and the end
materials are used for tissue engineering and
user. These organizations may not be directly
provide proper environments for cell growth
involved in the development of a specific
and differentiation. They also have special
treatment using the standard approaches of
mechanical properties depending on their
regenerative medicine.
purpose.
A. Equipment Suppliers
C. Implants
This group of companies is specialized in the
A medical implant is a device introduced
production of equipment for cell and tissue
into the body to replace a missing biological
culturing. The range of necessary equipment
structure, and/or to support or enhance the
is rather wide. It includes cell culture hoods,
function of a damaged biological structure.
incubators, microscopes, centrifuges,
Implants as defined by regenerative medicine
refrigerators, freezers, etc. As an example,
are composed of biomaterials, but they
the laminar flow hoods provide an aseptic
should be described separately due to their
11
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
importance. Surgeons have used different
regenerative medicine. Information systems
mechanical implants for a long time. However,
help integrate and update the research on
these implants do not mimic human tissues
biological processes, which then forms the
as the materials used have properties that are
basis of research and development for new
different from biological material. At present, it
products in the Life Science industry.
is possible to construct implants from materials
foreign to the human body which can be used
as a scaffold for the attachment and growth
Segment 3.
of human cells. It has now became possible
to combine stem cells and foreign material
Molecular Induction
implants to derive a cell-based implant with
Technologies
mechanical properties that is better than the
mechanical implant alone. These implants
One possibility for the regeneration of
are also less susceptible to rejection by an
damaged human cells in case of a disease is
organism (Smith et al, 2012).
to transform them to circumvent this damage.
For example, if a cell produces a faulty protein
D. Cell and Tissue Sources
which results in a specific disease type, we can
inject the gene coding to produce the correct
The sourcing of donor cells, specimens,
protein. Another possibility is to transform stem
and other biological material is a necessary
cells from a patient’s own body and allow
factor in the development of regenerative
them to differentiate into a specific subtype,
medicine products. Companies specialized
replacing the damaged cells. In this chapter,
in providing reliable biological material which
we shall discuss different factors that can be
is well characterized and meets the required
used to induce the transformation of damaged
regulatory standards form the foundation
or diseased cells.
of the Enabling Technologies classification.
These characterized biomaterials can be
All transforming factors can be divided into two
used for different purposes, such as clinical
groups. The first group is that of the different
and scientific research or pharmaceutical
vectors used in gene therapy. The second
assays. The list of common bio-specimens
group is classified as the small molecules
includes donor cells, cell lines, frozen tissue,
and different biological proteins which can be
etc. All biological samples should be well-
introduced into the cells, resulting in a specific
characterized and obtained from reliable
transformation.
sources.
A. Gene Therapy (Vectors)
E. Information Systems
Gene therapy addresses the correction or
In the present-day Life Science industry,
an improved regulation of a mutated or
information systems play a vital role. For
defective gene by introducing nucleic acids
example, the modern field of bioinformatics
(DNA or RNA) as therapeutic molecules for the
could not exist without such systems.
correction of a specific defect. Gene therapy
Regenerative medicine is not an exception
can be used to add a new gene to a human
to this rule. Handling of large scale data
genome or to replace, correct or knock out a
regarding gene sequences, signaling
damaged gene. Nucleic acids, which are used
pathways, and mechanisms of actions of drugs
as therapeutic agents, should be packaged
on specific pathways all utilize the resources
within a specialized carrier, called a vector, in
of information systems to comprehend and
order to reach the cell nucleus and express a
study valuable data. Companies involved
desired protein product. Finally, all delivered
with the management and interpretation
DNA and RNA transform into functional
of large volumes of such data related to
proteins or RNA which can change behaviors
biological processes are an extremely
of the treated cells.
important component for the development of
12
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
molecules including naked DNA,
liposomes, inorganic nanoparticles,
and other structures, such as
dendrimers. The efficiency of these
methods has been enhanced since
they were first discovered, and
their main advantage lies in low
immunogenicity and an ease of large
scale production.
Their therapy can be classified as
somatic cell gene therapy, where
only somatic cells in the body are
manipulated, and the gene defect
is still passed on to the future
generations.
The second type is germ line gene
therapy, where human germ cells
are modified, the genetic defect is
corrected, and the corrected gene
is passed on to future generations.
Unfortunately, germ line gene
therapy has not yet been completely
validated for safety and remains
forbidden in several countries.
Gene therapy is suited for diseases
caused by single-gene defects.
There are at the present time a
large number of gene therapy trials
targeting cancer and hereditary
diseases. Targeting genetic defects
resulting from a combination of
There are several types of vectors which
several faulty genes is still deemed difficult and
can be classified into two subtypes:
has not been widely investigated.
Viral Vectors and Non-Viral Vectors.
Until 2012, more than 1800 clinical trials
a. Viral Vectors
involving gene therapy have been successfully
The first possibility to deliver nucleic acids into
completed (Ginn, Alexander, Edelstein, Abedi,
a cell is through the use of different viruses.
& Wixon, 2013) in more than 31 countries.
Viruses can penetrate into the cell and nucleic
There are also a number of ongoing clinical
membrane and deliver genetic material which
trials evaluating the potential of gene therapy
is then expressed by the cell. If a part of a viral
methods (URL Ref. 5). For example, the first
genome is replaced with a gene of interest, this
gene therapy trial was conducted on a 4
gene will be expressed by the cells, instead of
year old girl at the NIH center in the USA
the viral genes. Different types of viruses such
on 14 September 1990 for the treatment of
as adenoviruses, retroviruses, and lentiviruses
adenosine deaminase deficiency
are widely used for human gene therapy.
(URL Ref. 6).
b. Non-Viral Vectors
Although there are a number of clinical trials
reporting success, the method has some
Non-viral vectors are comprised of small
serious disadvantages. The efficacy of many
13
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Chart 3: Funding for projects in gene therapy.
gene therapies is not long-lasting, especially
investigated.
for somatic cell gene therapy. The second
The funding of projects to study and test gene
disadvantage is the immune response to the
therapy has seen a sharp increase since the
treated cells, as they carry fragments of DNA
year 2007, and the funding reached almost $5
which are recognized by the host as ‘non-self.’
billion for the year 2010. (URL Ref. 7)
Furthermore, the use of viruses can also elicit
an immune response, at times incapacitating
B. Small Molecules and Proteins
the mode of delivery. The use of integrating
viruses, which integrate the DNA into the host
Another promising approach for the
DNA, can be tumorigenic, as the site of DNA
treatment of diseases is to introduce small
integration is unpredictable, and might affect
molecules such as growth factors or other
the normal cellular processes and functioning
specific proteins in the body to allow for the
of cells. Several strategies to overcome these
regeneration of a damaged or diseased tissue.
potential disadvantages are currently being
Different proteins and small molecules can be
Chart 4: Funding received by projects in regenerative medicine exploring growth factors and small molecules.
14
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
growth factors. (URL Ref. 8)
C. Combination of Gene
Therapy and Small Molecules
and/or Proteins
Combining gene therapy with small
molecules or protein therapy can reduce
the side effects of gene therapy alone and
improve its efficacy. For example, when
adenoviruses are used as vectors, they have
a strong hepatic tropism, strongly reducing
the safety and efficacy of the therapy.
Recently, scientists have discovered several
small molecules which can circumvent
this side effect and make the therapy
safer (Duffy et al, 2013). This approach is
very promising and will probably have
widespread applications in the future.
Segment 4.
Cells
The human body consists of more than
1013 (10,000,000,000,000) cells of several
different types. These differences in
different cell types are both morphological
and functional.
Different cell types display stark differences
used for these purposes.
in the pathways used for cell signaling,
though they may have structurally similar
For example, Platelet Growth Factor (biological
compositions.
protein which is contained in platelets) can
be used for treatment of non-healing wounds
All cells in a human body are derived from a
and for regeneration of bones (Burnouf et al,
single fertilized egg cell. Most of the cells in
2013). Small molecules have also been used
an adult human body are mature cells without
for the regeneration of bones (Lo, Ashe, Kan,
the capacity to proliferate, but can perform a
& Laurencin, 2012). Recently, scientists have
specialized function in the body.
discovered that small molecules and proteins
After a certain number of cell cycles, a mature
can be used to reprogram mature cells
cell cannot divide any further and hence,
into stem cells. These stem cells are called
is unable to regenerate when afflicted by
induced pluripotent stem cells (iPSCs) and
damage or disease. Stem cells have two main
have the potential to revolutionize the field of
features that make them suitable to replenish
regenerative medicine. These will be discussed
the lost adult cells. Stem cells can proliferate
separately.
and generate a large number of identical
The funding of projects on regeneration which
daughter cells, making them suitable to be
use small molecules and growth factors has
used for regenerative purposes.
also seen a sharp rise since 2007. However, the
Secondly, stem cells are capable of being
funding for projects which use small molecules
transformed into many specialized cell types.
for regeneration is much less than those using
15
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
embryo. At this stage, the embryonic
cells can form all cell subtypes
found in a human body, along with
the cells forming the placenta, for
the attachment of the embryo to the
mother’s uterus. After several days,
the cells in an embryo divide and
form a blastocyst. At this stage, the
embryo consists of a trophoblast
and an embryoblast. The trophoblast
is an outer layer of ancillary cells
which provide nutrients and form the
placenta.
The embryoblast or the inner cell mass
contains cells which are capable of
differentiating into all cell subtypes in a
human body.
Due to their potential to differentiate,
these cells are called Embryonic Stem
Cells (ESCs), and they are valuable
because they can help to restore any
type of human cells.
In order to get ESCs, the blastocyst
is destroyed, and the inner cell mass
is extracted. Thereafter, the cells are
cultivated to generate a stable cell line.
The process of cultivating stem cells is
rather difficult and time intensive, and
often, additional cells are added into
the medium to support the growth of
these ESCs. These additional cells can
Stem cells in general can also be classified into
be of a xenogenic origin and thus, the clinical
several subtypes depending on their lineage.
usage of derived ESCs is limited because of a
For example, mesenchymal stem cells, cardiac
high risk of rejection.
stem cells, embryonic stem cells, and so on.
Each subtype of stem cells has its own set of
In order to get specifically differentiated cells
advantages and disadvantages, which will be
(for example fibroblasts), the ESCs are placed
discussed in later sections. The regenerative
into a special medium containing chemicals
capacity of stem cells, as employed in cell
which help the ESCs differentiate into the
therapy, undoubtedly makes them the most
necessary cell types.
important factor in the field of regenerative
medicine, as they have enormous medical and
As ESCs are pluripotent i.e. they can transform
economic potential.
into any type of human cells, they are
promising for clinical purposes. They can be
A. Embryonic stem cells (ESCs)
transformed into cells such as cardiomyocytes,
fibroblasts, chondrocytes, hepatocytes, etc.,
As was mentioned before, cells in a human
paving the way for treatment of diseases
body are derived from the zygote, formed
such as cardiovascular diseases, diabetes,
after fertilization of an egg and a sperm. After
neurological diseases, etc. The FDA approved
fertilization, the zygote divides to form an
16
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Chart 5: Funding received by projects dealing with embryonic stem cells.
the first clinical trial of ESCs in 2009 for the
formation of tumors. New methods of ESC
treatment of spinal cord injury, a treatment
cultivation and clinical use of ESCs are
developed by Geron Corporation (Falco,
underway, and a breakthrough is expected in
2009). The company declined to schedule
the near future.
subsequent trial stages because of an internal
According to FundingTrends.org, the funding
change in strategy.
of projects using ESCs sharply increased since
Although ESCs are promising, there are
2007.
several technical and ethical issues related to
(URL Ref. 9)
the development of stem cell therapies. In
B. Induced Pluripotent Stem Cells (iPSCs)
previous times, a scientist had to destroy an
embryo to retrieve ESCs, and thusly, their
Induced Pluripotent Stem Cells are stem cells
usage for research has raised a number of
artificially derived from mature human cells by
ethical and legal questions. In some countries,
inducing an overexpression of several
stem cell research using human embryos is
specific genes. The possibility of transforming
forbidden.
mature somatic cells into stem cells was
demonstrated by Shinya Yamanaka and his
However, there is now a way to get ESCs
team in 2006, and they managed to produce
without destruction of an embryo, and this
human iPSCs in 2007. In 2012, Shinya Yamanaka
new method can help to solve most of the
was awarded the Nobel Prize in Physiology or
ethical and legal problems encountered thus
Medicine for his discovery.
far. Earlier, xenogenic components were
used during the cultivation of ESCs, which
iPSCs are produced from somatic cells,
could result in a rejection of the induced stem
and the new discovery paves the way for a
cells, and at the same time, was a risk for
novel method of deriving stem cells without
transmission of diseases from a foreign animal
destroying an embryo. This method therefore
source. However, it is now possible to generate
doesn’t raise any ethical issues. Another
ESCs without the use of xenogenic elements.
important aspect of iPSCs lies in the fact that
they can be directly derived from a patient’s
The third major problem associated with the
own cells, and consequently, the chances of
use of ESCs is the development of tumors in
rejection after transplantation is unlikely.
the patients, as not all the cells introduced into
the body have been specifically differentiated
The process of reprogramming mature cells
and the non-differentiated cells result in the
to derive iPSCs initially was reported using
17
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
four specific genes. It has now
been shown that all of these four
genes may not be required for
successful reprogramming. This
finding is extremely significant,
as some of the genes reported
are oncogenes and could cause
cancer.
There are several ways to start
the transformation process,
with each of the methods
having its own advantages
and disadvantages. First of all,
different types of vectors can
be used to deliver the genes for
reprogramming. A vector delivers
the necessary genes into a cell
and makes it transform into a
stem cell. Some of the delivered
genes can be oncogenes, and
this is why usage of such iPSCs
in real world applications is
considered dangerous. Moreover,
some of the vectors used (such
as plasmids and retroviruses) can
integrate into the human genome
and result in unpredictable
mutations.
Another approach is to use
microRNAs, which are small RNA
molecules with an ability to bind
Chart 6: Funding volume index
for induced pluripotent stem cells.
18
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
to specific mRNA sequences, primarily at the
3’ end, and thus regulate gene expression
(Bao et al, 2013), along with the assistance
of proteins and small molecules (Science
daily, 2009; Cyranoski, 2013). These methods
for reprogramming are relatively safer, as
there is no modification of the genome, and
as a result, mutations are unlikely. Moreover,
the efficacy of these methods can be similar
or higher than that reported for the other
methods.
iPSCs have properties very similar to
embryonic stem cells (although there are
some differences). For example, if one
replaces the embryonic stem cells in a mouse
embryo with iPSCs, the embryo grows into a
normal mouse.
This implies that iPSCs can be used to
derive cells of a specific subtype, i.e. for
the treatment of cardiovascular diseases,
diabetes, neurological diseases and a number
Although iPSCs hold a promise for the future
of other diseases with any type of damaged
of regenerative medicine, there is a high risk
cells.
of developing mutations and cancer with
The first clinical trial of iPSCs was approved in
them. The efficacy of reprogramming adult
Japan on 19 July 2013 (Cyranoski, 2013).
cells into iPSCs is rather low. The process
of transformation is rather difficult and can
Presently underway, the investigation shall
sometimes result in an incomplete gene
be transforming human cells from the skin
expression.
into retinal pigment epithelial cells to be used
for the treatment of age-related macular
According to FundingTrends.org, funding
degeneration.
of projects using iPSCs has dramatically
Chart 7: Funding volume index
for adult stem cells.
19
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
increased since the year 2007.
hematopoietic stem cells, umbilical cord blood
stem cells, intestinal stem cells, mesenchymal
C. Adult Stem Cells (ASCs)
stem cells, neural stem cells, olfactory adult
stem cells, and others. Some are widely used
Adult Stem Cells (or Somatic Stem Cells)
in clinics, while others are at present being
are stem cells found in a juvenile or an adult
evaluated for safety and efficacy of usage. The
human body.
most important types of adult stem cells will
These cells are multipotent with a capacity
be discussed in later sections.
to differentiate into a limited number of cell
Most ASCs are rare, and therefore, it is difficult
types, rather than all types of human cells.
to isolate them. Moreover, cultivating ASCs
Usually they differentiate into the cells of
in the laboratory has proven to be rather
the same germ layer. Sometimes, they can
difficult. Another drawback is that the method
transform into the cells of another germ layer.
of obtaining these stem cells often involves
This phenomenon is referred to as Trans-
serious damage to the organs and tissues (for
Differentiation or Plasticity.
example, isolation of heart stem cells).
The function of ASCs in the body is to
It is possible to transplant ASCs from one
regenerate specific tissues (they regenerate
individual to another, but it is obligatory to use
the tissue where they are presented). They
immunosuppressive therapy in order to avoid
are classified into different types of ASCs, i.e.
rejection.
Chart 8: Funding of projects on mesenchymal stem cells (MSCs)
20
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
According to FundingTrends.org, funding of
vessels, but they activate the precursors of
projects using ASCs has sharply increased
endothelial cells, which form the inner layer of
since 2007.
all blood vessels.
a. Mesenchymal Stem Cells
There are a number of early stage clinical
trials validating the ability of MSCs to
Mesenchymal Stem Cells (MSCs) were
induce neovascularization. There are also
originally found in the bone marrow.
some reports indicating that MSCs can be
Thereafter, they were also isolated from the
transplanted from one patient to another
fat tissue, muscle tissue, and other places.
without any risk of rejection, and moreover,
However, there is no evidence that the cells
it has been demonstrated that MSCs can be
from other sources are similar to the cells from
used as an immunosuppressant. All of these
bone marrow.
reported studies are in the preliminary stages
and require further evidence to prove the
Bone marrow is a source of several
efficacy of MSCs.
different cell types (amongst them are the
Hematopoietic Stem Cells which shall be
According to FundingTrends.org, funding of
discussed later), but only 0.001-0.01% of them
projects using MSCs considerably increased
qualify as MSCs, making their isolation process
since 2007.
time intensive and difficult.
b. Hematopoietic Stem Cells
MSCs from the bone marrow can differentiate
only into three cell types i.e. adipocytes (fat),
Hematopoietic stem cells (HSCs) have the
chondrocytes (cartilages), and osteocytes
capacity to form all types of blood cells. The
(bones). Differentiation of MSCs into other cell
population of hematopoietic stem cells contain
types is not validated or the derived cells are
different cells, some of which are multipotent,
often non-functional.
and some of which are oligopotent and
unipotent. The main source of hematopoietic
MSCs can be used in treatment of local
stem cells is the bone marrow. HSCs can
skeletal defects. They also have the potential
also be harvested from umbilical cord blood,
to repair cartilages. Another area where MSCs
peripheral blood, and amniotic fluid. HSCs
can be helpful is treatment of heart and blood
can be frozen and stored for years in special
vessels. MSCs can induce neovascularization,
cryofreezers.
which is the process of forming new blood
vessels. MSCs themselves do not form new
Hematopoietic stem cells are used for
Chart 9: Funding for hematopoietic stem cells
21
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
transplantation. This procedure
is often performed on patients
with cancer of the blood or bone
marrow. Before transplantation,
radiation and chemotherapy are
used to weaken the immune
system of a recipient in order
to avoid rejection, and to kill
malignant cells.
The graft can be autologous
or allogeneic. In case of an
autologous graft, HSCs are
collected from the patient before
complete or partial weakening of
his bone marrow, and then the
transplantation is performed. The
advantage of this method is a low
More than 50,000 hematopoietic stem cell
risk of rejection, but the risk of relapse (as the
transplantations (HSCTs) are performed
graft can contain malignant cells) rises.
annually, of which more than half are
autologous. Other are allogeneic and the total
The allogeneic graft can be safer in some
number of HSCTs continues to increase at a
cases, but is associated with issues such as
rate of 10-20% every year (Perumbeti, 2013).
the graft-versus-host disease, which is when
the immune cells of the graft begin to attack
Although HSCTs are common, they have been
the implanted tissues. It is also difficult to find
associated with a risk of infection and graft-
a suitable donor with similar human leucocyte
versus-host disease. They are commonly
antigen (HLA). HLA is a molecule expressed
used only for the treatment of life-threatening
on a cell surface (also referred to as the major
diseases such as leukemia. Improved
histocompatibility complex MHC). The HLA of
outcomes have been attributed to better
the donor and HLA of the recipient should be
safety standards and a reduction in the number
similar in order to avoid immune conflict.
of infections and other negative outcomes.
Chart 10: Funding in the field of umbilical cord blood stem cells.
22
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
According to FundingTrends.org, funding of
umbilical cord is rather easy, the amount of
projects using HSCs steadily grew since 1991
blood harvested from the cord is rather small.
up to 2010.
Usually, this amount is enough to treat a child,
but not enough to threat an adult person. To
c. Umbilical Cord Blood
solve this problem, it is possible to harvest
Stem Cells
cells from multiple umbilical cords or from
the placenta. There is also an opportunity to
Umbilical Cord Blood Stem Cells (UCBSC) are
cultivate UCBSCs in vitro.
derived from the blood in the umbilical cord
and placenta after a baby is born. They can
Cord blood is used to treat different types of
be easily collected, with no risk to the baby or
blood cancer or to treat genetic blood diseases
mother.
like Fanconi Anemia. About 20,000 umbilical
cord blood transplants have been performed
Cord blood contains hematopoietic stem
Chart 11: Funding for amniotic stem cells.
up until 2013 (Gupta, 2012). Several attempts to
cells, along with other types of stem cells, but
use UCBSCs in the treatment of other diseases
additional studies are required to confirm this
have not been successful. For example, a
finding.
clinical trial studying cord blood treatment for
Although the process of collecting from an
diabetes failed to show any improvements. At
Chart 12: Funding related to artificial cells.
23
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
present, there is an active clinical trial
exploring the benefits of UCBSCs in the
treatment of child brain disorders and
traumatic brain injury, but the results
have proven controversial.
Cord blood banks provide the facilities
to freeze and store the umbilical cord
blood over long periods of time. There
are two types of cord blood banks:
public and private. Public cord blood
banks work for the benefit of the
general public, while the private cord
blood banks are usually profit-making
organizations, and cord blood stored in
these banks is used exclusively by the
client donors or the donor’s relatives.
The benefit of a private cord blood bank
is a controversial issue because the
probability of the original donor ever
using their own cord blood is often very
low.
According to FundingTrends.org,
funding of projects using UCBSC
reached a peak in 2009.
d. Amniotic
Stem Cells
Amniotic Stem
Cells are derived
from the amniotic
fluid. Amniotic
fluid is a protective
liquid surrounding
a fetus. Amniotic
stem cells
are primarily
composed of
mesenchymal
stem cells with
a capacity to
differentiate into
Chart 12: Funding in tissue engineering.
various types of
human cells.
According to FundingTrends.org, funding of
projects using amniotic stem cells reached a
Amniotic stem cells can be collected without
peak in 2009.
destroying an embryo, but there is a very small
risk of pregnancy loss. Overall, the use of
e. Artificial Cells (ACs)
amniotic stem cells has not been associated
Artificial Cells are engineered constructs which
with any ethical problems. Many banks now
mimic some cell functions and are non-living
provide the facility to store amniotic stem cells.
24
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
entities. An example of an artificial
cell is a liposome. Liposomes
have a lipid membrane like living
cells and can be used to mimic
cells and deliver molecules such
as nucleic acids, proteins, and
small molecules.
As the surface of these artificial
cells lacks antigens, they can be
useful where immunogenicity
is a problem. They can help to
avoid immune system rejection.
For example, it is possible to
encapsulate stem cells into
artificial cells and use them as
carriers. Artificial cells can also
be used for transporting different
drugs and nucleic acids (DNA and
RNA).
According to FundingTrends.org
funding of projects using artificial
cells reached a peak in 2008.
Segment 5.
nutrition, and special mechanical features of
Tissues
the tissue.
Tissue is the next level of organization of
All tissues are classified into four types, i.e.
our body after cells. Every tissue consists
the connective tissue, the muscle tissue, the
of a group of specialized cells and an
epithelial tissue, and the nervous tissue.
extracellular matrix supporting these cells in
a 3-dimensional structure. The extracellular
Regeneration of tissues is an important and
matrix is produced by the cells and plays a
challenging issue, as one has to recover not
very important role in cell communication,
only cells, but also the extracellular matrix.
Today it is possible
to regenerate
bones, cartilages,
skin, muscles, and
other tissues.
There are several
approaches to
tissue engineering
which shall be
discussed in later
sections.
According to
FundingTrends.org,
funding of projects
2C
hart 13: Funding for projects using the scaffold technique.echnology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
for tissue engineering has risen considerably
According to FundingTrends.org, funding
since 2007.
of projects using the scaffold technique
increased in 2007.
A. With Scaffold
B. Without scaffold
The most popular technique used in
tissue engineering is scaffold-based
There is an alternative method to 3D printing
tissue regeneration. There are three main
without the use of scaffolds. In this method,
components to this approach. The first one is
small bio blocks are used as three-dimensional
a scaffold. A scaffold is defined as a biologic,
pixels. These blocks consist of different cells
synthetic or semi-synthetic matrix with
derived from a donor, and their composition
special mechanical properties. It provides a
can be precisely controlled.
necessary microenvironment for cell growth
Once they are put together, they fuse to form a
and differentiation. The second component is
new tissue (Mironov et al, 2009).
the stem cell cluster, and the third component
is formed by different molecular induction
factors which are necessary for cell growth and
Segment 6.
differentiation.
The process of regeneration of any tissue
Organs
consists of several stages.
The Organ level is the next level of organization
in the human body. Every organ consists of
1.
Harvesting of stem cells from a donor. (It
different tissues and has a higher level of
can also be induced pluripotent stem cells.)
structural complexity than observed at a tissue
2. Cultivating of the derived
level. Due to a higher level of complexity in
stem cells.
organization, regeneration of whole organs
is a much more complicated task than
3. Combining of the scaffold, stem cells, and
regeneration of tissues. There are a number
induction factors.
of promising results on animal experiments
relating to tissue engineering of complete
4. Tissue organization.
organs, and this field is believed to contribute
5. Transplanting of the graft.
to the growth of regenerative medicine in the
future.
There are some modifications of this method.
For example, tissue can be formed in vivo
A. Kidney
rather than ex vivo. One can introduce a
At present, there is no data on a complete
scaffold in the place where regeneration
lab-grown human kidney, but scientists have
is required and treat it with stem cells and
attempted to combine conventional renal
induction factors, and the tissue grows inside
filters with bioreactors seeded with renal cells.
the body.
Renal epithelial cells have the ability to provide
The results of this technique are promising
metabolic, endocrine, and immune functions,
and probably will be widely used in future
and the renal filters produce urine. Stem cells
applications.
can have a significant role in compiling an
artificial kidney as an unlimited source of renal
Another modification of the scaffold-based
cells (Tasnim et al, 2010).
method is 3D bioprinting. This technique
utilizes special 3D printers to form the tissues
Animal experiments have also shown
from biomaterials and cells. At present,
promising results in experiments attempting
scientists are developing 3D bioprinting
to create a new kidney using decellularized
facilities aimed at printing whole organs rather
kidneys from a xenogenic source or a donor
than tissues.
(Yong, 2013). This process encompasses the
stripping of cells from a donor kidney using
26
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
specialized detergents to get a connective
construct blood vessels and heart valves using
tissue scaffold. The decellularized scaffold is
decellularized scaffolds.
then seeded with human umbilical cord blood
E. Skin
stem cells (for the development of vessels)
and with the kidney cells from newborn
Tissue-engineered skin is already available
rats. The transplant can grow in a special
and widely used in clinics, for example, for
incubator and was shown to be functional after
the treatment of non-healing wounds. These
transplantation, although not as efficiently as a
transplants can mimic all layers of the skin or
normal kidney.
just one of the layers, as desired. They can be
cellular or acellular. Some of them are derived
B. Liver
from autologous sources while others are of
A lab-grown human liver has made
allogeneic or even xenogenic origin.
considerable progress using decellularized
F. Pancreas
scaffolds and stem cells, as described in the
previous section (Uygun & Yarmush, 2013). In a
Recent experiments on animals to produce a
recent study, scientists created a vascularized
lab-grown pancreas are promising (Science
and functional human liver using iPSCs to
daily, 2012). Researchers have succeeded in
derive specific hepatic cells, human umbilical
growing small functional parts of a pancreas
endothelial cells (for development of vessels),
with the ability to produce insulin after
and human mesenchymal stem cells (for the
transplantation. They used special scaffolds
development of connective tissue matrices).
and pancreatic cells from a healthy donor.
All of these cells were combined in a dish,
They also used umbilical cord blood cells for
where they self-organized into macroscopic
the development of vessels. It was found from
cell clusters. Upon transplantation, these
these studies that vascularization is a key to a
clusters were functional and showed good
successful transplantation of the pancreatic
vascularization (Takebe et al, 2013).
tissue.
C. Bladder
G. Trachea
A bio-engineered bladder has already been
The first bio-engineered trachea has
created and successfully transplanted using
already been constructed and successfully
a biodegradable scaffold and cells from the
transplanted. It was performed by Paolo
bladder, along with muscle cells to generate
Macchiarini in 2008 using adult stem cells from
a new bladder (Khamsi, 2006). However,
bone marrow, which were transformed into
there are several problems concerning the
cartilage cells. A decellularized segment of a
functionality of the transplanted bladder that
cadaveric trachea was used as a scaffold in
are currently being worked on (Horst et al,
these experiments. In these experiments, the
2013).
vascularization of the trachea was observed as
early as one month after transplantation.
D. Cardiovascular System
H. Teeth
In successful experiments on rats, scientists
used decellularized hearts as scaffolds
Usage of stem cells for the regeneration
(Maher, 2013). In order to construct a new
of teeth is a relatively new approach, but
heart, one needs at least two types of cells.
currently, there are some advances in this field.
These are endothelial precursor cells (for the
For example, studies on animal models are
development of vessels) and heart muscle
being conducted in order to understand the
precursor cells. In the experiments, these cells
mechanism of the regeneration of teeth (Wu et
were derived from iPSCs. The engineered
al, 2013). Most likely, in the future, this research
hearts were shown to be functional but
would help the development of a translational
their efficacy was too low for a successful
therapy for humans. At present, the most
transplantation. At present, it is also possible to
interesting experiments on teeth regeneration
27
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
are aimed at using induced pluripotent stem
A. Cardiovascular Diseases
cells (iPSCs) (Cai et al, 2013). Usage of iPSCs is
Cardiovascular diseases (CDVs) are diseases
not connected with any ethical issues or with
which affect the cardiovascular system,
problems of rejection, making the approach
including the heart and blood vessels. The list
attractive for many investigators.
of cardiovascular diseases includes coronary
I.
Bones and Cartilages
heart disease, cerebrovascular disease,
rheumatic heart disease, and congenital heart
Different types of grafts are already in use
diseases, amongst many others.
in clinics, the main types are allografts and
autografts. Special scaffolds and adult stem
According to the World Health Organization,
cells are used for these purposes. These days,
cardiovascular diseases are the leading cause
Chart 14: Projected U.S. Healthcare Costs by age group
scientists are trying to create entire bones
of death in the world, and it is estimated that by
using 3D bioprinters.
the year 2030, more than 23 million people will
die of cardiovascular diseases annually (URL
Ref. 10).
Segment 7.
Often, there are no symptoms associated with
cardiovascular diseases until the occurrence
Diseases
of acute events (for example, a heart attack).
The main goal of regenerative medicine is to
After such events, patients need life-changing
treat different diseases, some of which are
treatment, such as a surgical operation. After
extremely severe and can seriously affect
the treatment, a number of patients suffer from
a patient’s life. An effective treatment of
long-term disabilities, loss of productivity, and
such diseases can bring benefits not only
a low quality of life.
to patients, but also to global economics,
as it can seriously reduce healthcare costs.
Regenerative medicine can bring plenty of
According to the Alliance for Regenerative
benefits to the treatment of cardiovascular
Medicine, healthcare costs in the USA alone
diseases, and there are a number of
are expected to increase tremendously by
regenerative products in the market catering to
2030, especially for the elderly population. In
cardiovascular treatments.
this chapter, we highlight several important
Some available products:
diseases and the role of regenerative medicine
in their treatment.
1.
Amorcyte (a NeoStem company) is an
28
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
autologous bone marrow derived stem
C. Blood Diseases
cell product designed for the treatment
Blood diseases include different types of
of damaged heart tissue following acute
anemia, cytopenias, coagulopathies, and other
myocardial infarction. A Phase 2 clinical trial
associated diseases of the blood. Regenerative
of the product has already begun.
medicine has a huge potential in the treatment
2. The company VentriNova uses small
of different blood diseases, as all blood cell
molecules and gene therapy to induce
types originate from a single progenitor,
heart cells and to make them repair
the pluripotent hematopoietic stem cell.
the damaged heart tissue. Their lead
These cells have been widely used in clinics
product, which targets the Cyclin-A2 gene
for some time. For example, bone marrow
is currently in the preclinical stage of
transplantation is used for the treatment of
development.
several forms of anemia.
According to the Alliance for Regenerative
D. Wounds
Medicine, total inpatient hospital costs in the
Application of regenerative medicine for
USA for CDVs care were $71.2 billion in 2005.
wound healing forms a large part of the
Overall medical costs, which include medical
regenerative medicine industry. Non-healing
interventions, healthcare services, medications,
wounds are a focus of attention in regenerative
and lost productivity of the patients was
medicine, as these wounds do not undergo
reported to be $316 billion.
the normal healing process. These wounds can
(URL Ref. 11)
be caused by burns or are often associated
B. Cancer
with the presence of other medical conditions
such as diabetes. Conventional methods
The term “Cancer” comprises a large group
for the treatment of such wounds are often
of diseases, which are characterized by an
ineffective, and regenerative medicine can
uncontrollable cell growth. They invade and
bring considerable benefits.
damage nearby tissues and can spread or
metastasize to distant parts of the body,
Some available products:
forming secondary tumors. According to the
1.
Organogenesis has developed a cellular
World Health Organization, cancer is the third
product which is called Apligraf. It is a
leading cause of death in the world.
bi-layered graft composed of a layer
Transplantation of hematopoietic stem cells
of mature keratinocytes and a layer of
is widely used in clinics for the treatment of
fibroblasts in a collagen matrix. The efficacy
blood cancer. Scientists are also trying to use
of Apligraf has been proven, and in 2012,
adult stem cells for the regeneration of lost
the company sold more than 500,000 units.
tissue after a surgical resection of tumor. There
2. Avita Medical has developed a product
are also a large number of gene therapies at a
which is called ReCell Spray-On Skin. It is
preclinical or clinical testing stage for different
an autologous cell technology where the
types of cancers.
product can be sprayed onto a wound. This
Cancer is associated with huge economic
product is proven to accelerate the healing
burdens to society. According to the American
process and minimize scar formation. It is
Cancer Society in the USA, overall annual costs
already available in Europe, Canada, and
of cancer were $201.5 billion in the year 2008.
Australia.
Direct medical costs were estimated to be
According to the Alliance for Regenerative
$77.4 billion and indirect costs (cost of loss in
Medicine in the USA, the annual costs
productivity because of premature death) were
associated with the treatment of non-healing
$124 billion.
wounds is about $35 billion, which is expected
to increase to $200 billion by 2020.
29
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
E. Reproductive System Diseases
According to the Alliance for Regenerative
Medicine in the USA, annual combined direct
Stem cell therapy has a huge potential in
and indirect costs associated with PD are
reproductive medicine, as it was discovered
about $23 billion.
that ovaries contain stem cells, which can
differentiate into new oocytes. Previously, it
Spinal cord injuries often lead to quadriplegia
was believed that ovaries contain a limited
or paraplegia and have a strong negative
number of oocytes. Extraction and cultivation
impact on the life of the patient. At present,
of ovarian stem cells can be used for the
there are several commercial products which
treatment of infertility, and there have
could help with the treatment of spinal cord
also been attempts to use bone marrow-
injuries. Some of them are based on the use
derived stem cells for the regeneration of
of stem cells, which can differentiate into the
endometrium tissue (Duke & Taylor, 2013).
various cells of the nervous system; others
use special scaffolds to provide appropriate
F. Neurological Diseases
conditions for the regeneration of spinal cord
nervous tissue.
Neurological diseases encompass diseases
which affect various parts of the nervous
According to the Alliance for Regenerative
system. Often, these diseases are hard to cure
Medicine in the USA, annual costs for the
and very expensive for the health care system.
treatment of one patient after a spinal cord
The list of neurological diseases includes
injury is more than $320,000 for the first year
Alzheimer’s disease, Parkinson’s disease,
after the injury, and more than $39,000 for
spinal cord injuries, etc. Regenerative medicine
subsequent years.
could significantly improve the lives of patients
suffering from neurological diseases.
G. Ocular Diseases
Alzheimer’s disease (AD) is the most common
Ocular diseases affect the human vision
disease associated with the loss of memory
system and include diseases such as age-
and intellectual abilities. The majority of
related macular degeneration (AMD), cataracts,
patients are above 65 years of age. Scientists
and glaucoma, amongst others. Some of
have managed to create a human disease
these diseases can be treated by conventional
model of AD using reprogrammed donor cells.
methods, but regenerative medicine can
This model could help to find clues for the
bring a lot of benefits into this field. There are
treatment of this disease.
a number of promising animal experiments
which can lead to future treatment of the
According to the Alliance for Regenerative
diseases which cannot be treated now.
Medicine in the USA, annual costs associated
with providing care for people with AD are
Some available products:
about $200 billion, and these costs are
1.
Advanced Cell Technology has developed
expected to increase to $1.1 trillion by 2050.
a treatment for degenerative retinal
Parkinson’s Disease (PD) is a
disease. This technology uses retinal
neurodegenerative disease associated with the
pigment epithelial cells derived from
degeneration and death of neurons. Patients
human embryonic stem cells.
with PD suffer from tremors, poor balance,
2. StemCells Inc. has developed a product
and loss of movement control. Although
which can preserve the visual acuity
this disease is not lethal, it seriously affects
and protect the retina from progressive
the quality of life of the patients and their
degeneration in rats. This product uses
families. Scientists succeeded in constructing
neural stem cells. Phase 1/2 of clinical trials
a model of PD, and now they are trying to use
of this product began in 2012.
regenerative technologies to replace the dying
neurons and to improve the tropism of healthy
According to the Alliance for Regenerative
neurons.
Medicine in the USA, annual cost of care
30
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
for patients suffering from different ocular
2. MiMedix Group, Inc. has developed a
diseases is about $51.4 billion.
product which acts as a scaffold, assisting
the body in the generation of new tissue.
H. Gastrointestinal Diseases
Unfortunately, this product has not yet been
approved in the USA.
A number of regenerative technologies are
aimed at the treatment of different parts of the
According to Alliance for Regenerative
digestive tract. Some of these are associated
Medicine in the USA, annual healthcare costs
with the regeneration of large parts of our
of MSDs are about $850 billion.
gastrointestinal system, such as the liver and
the pancreas. Others are targeted towards the
K. Diabetes
treatment of different intestinal diseases such
Diabetes is a group of metabolic diseases in
as Familial Adenomatous Polyposis (FAP) and
which a patient suffers from high blood sugar
Crohn’s disease.
levels accompanied with several secondary
I.
Urinary System Diseases
factors. It is a chronic condition which can lead
to many different complications. For example,
There has been some research on
it can lead to cardiovascular problems, nerve
technologies for regeneration of different parts
damage, kidney failure, blindness, and diabetic
of the urinary system. For example, scientists
ulcers.
have already succeeded in the synthesis and
transplantation of a bio-engineered bladder
Diabetes is classified into two types:
(Khamsi, 2006). Presently, there are several
Type 1 (or insulin-dependent) diabetes is
companies aimed at treatment of urological
caused by insufficient insulin production
diseases. For instance, the company Tengion
resulting in elevated levels of blood glucose.
has a technology for the treatment of patients
Insulin is a hormone which regulates the level
after removal of the bladder. They have
of glucose in the blood and is produced by
also developed a stem cell technology for
special cells in the pancreas. If a patient has
augmenting and repairing the kidneys.
type 1 diabetes, these cells are attacked by a
(URL Ref. 12)
patient’s immune system, and as a result, are
J. Muscular and Skeletal Disorders and
non-functional. A decrease in the number of
Injuries
insulin producing cells results in insufficient
production of insulin, resulting in increased
Musculoskeletal disorders (MSDs) result from
levels of blood glucose. Currently this type of
injuries of joints, tendons, bones, cartilages,
diabetes is treated by injections of insulin.
and muscles. They are generally a result of a
sudden trauma or various prolonged physical
Type 2 (or noninsulin-dependent) diabetes
factors. Common symptoms of MSDs are pain,
is characterized by insulin resistance and
inflammation, and stiffness. The list of MSDs
relative insulin deficiency. Type 2 diabetes
includes such diseases as arthritis, tendonitis,
is treated by injecting insulin and by some
bursitis, etc. According to the Centers for
other medications. Balanced diet and regular
Disease Control and Prevention in the USA,
exercise have been shown to have a positive
more than 20 million people suffer from
impact in alleviating this condition.
arthritis.
Regenerative medicine can offer a more radical
Some available products for musculoskeletal
treatment of diabetes. Some technologies are
disorders include:
aimed at the regeneration of insulin producing
cells, while others try to mediate the immune
1.
The company Mesoblast has developed
system and prevent its attack on the insulin-
a treatment for degenerative disc disease
producing pancreatic cells. Gene therapy can
using mesenchymal precursor cells. The
also be helpful in the treatment of diabetes.
company is currently testing its technology
in clinic.
31
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Some available products targeting diabetes
2. Tigenix has two products derived from
include:
adipose tissue stem cells, which are
designed for the treatment of autoimmune
1.
Athersys Inc. has launched a preclinical trial
disorders. The first product, Cx601, is for
of their product, which is called MultiStem.
the treatment of Crohn’s disease. This
This product should mediate the immune
product is currently in the Phase 3 trial. The
system and protect pancreatic cells.
second product, Cx611, is targeted for the
treatment of rheumatoid arthritis and is in a
2. Mesoblast has developed a product
Phase 2 trial.
derived from mesenchymal progenitor
cells. This product can be helpful in both
According to the Alliance for regenerative
type 1 and type 2 diabetes. Mesoblast is
medicine in the USA, annual direct costs for
currently in a Phase 2 clinical trial of their
treatment of autoimmune disorders are about
product.
$100 billion.
According to the Alliance for regenerative
medicine in the USA, annual costs of caring
for patients suffering from diabetes was more
than $174 billion in 2007 and is expected to
increase to $336 billion by 2034.
L. Immunological diseases
The list of immunological diseases is huge
and includes several autoimmune disorders,
host versus graft disease, etc. Autoimmune
disorders occur when a previously healthy
immune system begins to attack healthy
tissues and destroy them, resulting in an
inflammatory response. Usually, the immune
system attacks the connective tissues, blood
vessels, joints, muscles, and endocrine glands.
The list of autoimmune disorders includes
lupus, rheumatoid arthritis, thyroiditis, and type
1 diabetes, amongst many others. The causes
of autoimmune disorders are unknown. There
are some technologies using stem cells which
can prevent such conditions.
Some available products:
1.
Celgene has developed a product aimed
at the treatment of different autoimmune
disorders. Placenta-derived stem cells are
used in this technology. The company has
already launched a Phase 2 clinical trial of
their product for the treatment of Crohn’s
disease and rheumatoid arthritis. They also
plan Phase 1 clinical trials for their products
targeting multiple sclerosis and sarcoidosis.
32
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Highlights of 2013
3
various applications. The collaboration will
focus on assessing laminin-based in vitro cell
culture matrixes offering highly physiological
microenvironments for living cells. Under the
terms, Roche will provide R&D funding and
scientific expertise to BioLamina company.
March 28, 2013
The Bellvitge Biomedical Research Instiŧute
Collaborations
(IDIBELL), Spain (www.idibell.cat) has signed a
licensing agreement with the Spanish biotech
Partnerships
company Histocell (www. histocell.com/en)
to make use of a patent for the treatment of
& Alliances
acute pulmonary diseases with mesenchymal
stem cells (MSCs). MSCs could be
administered intravenously and have the ability
January 3, 2013
to go directly to the damaged lungs, acting as
Cellular Dynamics International, WI, USA
a ‘smart drug’ without any risk of rejection. To
(www.cellulardynamics.com) announced an
enhance the effect, researchers have modified
agreement with AstraZeneca Company
these cells by genetic engineering to secrete
(www.astrazeneca.com) to accelerate the pace
IL-33.
of drug discovery through the use of human
induced pluripotent stem (iPS) cell lines and
March 4, 2013
tissue cells.
Life Technologies, CA, USA
(www.lifetechnologies.com) signed a
March 4, 2013
research and license agreement with Harvard
VistaGen Therapeutics, CA, USA
University, MA, USA (www.harvard.edu),
(www.vistagen.com) and Celsis In Vitro
under which the firm has acquired exclusive
Technologies, MD, USA (www.celsisivt.com)
rights to develop a panel of characterization
have agreed to collaborate on characterizing
assays designed to rapidly evaluate human
and functionally benchmarking VistaGen’s
pluripotent stem cells for their utility in a
human liver cell platform, LiverSafe 3D™, with
variety of discovery and translational research
Celsis products for studying and predicting
applications. The panel will be offered on the
human liver drug metabolism.
company’s semiconductor sequencing and
PCR-based genetic analysis platforms.
June 17, 2013
VistaGen Therapeutics, CA, USA
April 25, 2013
(www.vistagen.com), a biotechnology
Stemedica Asia, a wholly-owned subsidiary of
company dealing with development of stem
Stemedica Cell Technologies, CA, USA (www.
cell technology for drug rescue, predictive
stemedica.com), has entered into a definitive
toxicology, and drug metabolism screening,
licensing agreement with the Stem Cell and
presented key developments involving its
Cancer Institute, a division of PT Kalbe Farma
CardioSafe 3D™ and LiverSafe 3D™ bioassay
Tbk, Indonesia (www. kalbe.co.id), the largest
systems.
publicly listed pharmaceutical company in
southeast Asia. Under the terms of the agree­
March 6, 2013
ment Kalbe shall be the exclusive licensor of
BioLamina, Sweden (www.biolamina.com) and
Stemedica’s ischemia-tolerant adult allogeneic
Roche, Switzerland (www. roche.com) signed
mesenchymal and neural stem cells for use
a research and development agreement to
in clinical trials in Indonesia, Thailand, and
jointly develop new cell culture systems for
the Philippines. Kalbe’s Stem Cell and Cancer
34
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Institute will be responsible for organizing and
VA, USA (www.dna.com) have expanded their
funding clinical trials in southeast Asia.
partnership. Fibrocell is known for its FDA-
approved product LAVIV®, a wrinkle treatment
May 27, 2013
that involves extracting, multiplying and
injecting a patient’s own fibroblasts.
Epistem, UK (www.epistem.co.uk) and
ScandiDerma, Norway (www.scandiderma.
The new agreement broadens the existing
com) aim to develop together a new in vitro
collaboration to include potential treatments
human living skin-equivalent model for testing
based on engineered autologous fibroblast
inflammatory responses. Epistem’s expertise is
cells for the localized treatment of
in the regulation of adult stem cells in epithelial
autoimmune and inflammatory disorders. This
tissue, which includes the skin, hair follicles,
could lead to developing a potentially new
GI tract, breast, and prostate. ScandiDerma is
class of therapeutics.
focused on developing new dermatological
products from existing organic cells.
July 15, 2013
The collaboration is made possible through
Neostem, NY, USA (www.neostem.com) and
the UK’s innovation agency, the Technology
the University of California, San Francisco,
Strategy Board (www.innovateuk.org), and
CA, USA (www.ucsf.edu) have agreed to
Innovation Norway (http://innovasjonnorge.
collaborate on the development of human
no), following a successful application
regulatory T-cells for the treatment of Type 1
for funding in the Sustainable High-Value
diabetes, steroidresistant asthma, and organ
Chemical Manufacture Through Industrial
transplant rejection.
Biotechnology competition.
August 6, 2013
June 13, 2013
Cardium Therapeutics, CA, USA
Stemedica Cell Technologies, CA, USA (www.
(www. cardiumthx.com) has entered into
stemedica.com) have entered into a global
an agreement with Orbsen Therapeutics,
distribution agreement with Life Technologies,
Ireland (www.orbsentherapeutics.com) and
CA, USA (www.lifetech.com). Under the
the National University of Ireland, Galway,
terms of this agreement, Life Technologies
Ireland
will exclusively offer Stemedica’s ischemic
(www.nuigalway.ie) to utilize Cardium’s
tolerant allogeneic adult mesenchymal stem
Excellagen® (www.excellagen.com)
cells and neural stem cells for worldwide sale.
pharmaceutically formulated 2.6% fibrillar type
Stemedica stem cell lines will be sold under
I bovine collagen gel as a delivery agent for
the brand name Gibco® and are available to
Orbsen’s proprietary stromal cell therapy in
purchase for research works beginning of the
preclinical studies for the potential treatment
second quarter of 2013.
of diabetic foot ulcers.
June 17, 2013
August 12, 2013
NGM Biopharmaceuticals, CA, USA
Cardium Therapeutics, CA, USA
(www.ngmbio.com) and MedImmune, CA, USA
(www.cardiumthx.com) and Boston Children’s
(www.medimmune.com) have entered into
Hospital, MA, USA (www.childrenshospital.org)
an exclusive agreement to discover, develop,
have entered research collaboration to assess
and commercialize novel therapeutics from
the medical utility of Excellagen as a delivery
NGM’s enteroendocrine cell program for the
scaffold to seed autologous mesenchymal
treatment of Type 2 diabetes and obesity.
fetal stem cells for ex vivo engineering of
tissue grafts for transplantation into infants to
July 1, 2013
repair prenatally diagnosed birth defects.
Fibrocell Science, PA, USA
September 6, 2013
(www.fibrocellscience.com) and Intrexon,
35
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Novartis, Switzerland (www.novartis.com)
for refrigeration or freezing. The grafts can
has entered into an exclusive global licensing
be utilized right out of the package without a
and research collaboration agreement with
complicated thawing process.
Regenerex, KY, USA (www.regenerex.com) for
use of the Company’s novel Facilitating Cell
December 9, 2013
Therapy platform.
The Hamner Institutes, NC, USA
(www.thehamner.org) and Cellular Dynamics,
Facilitating Cell Therapy is a novel allogeneic
WI, USA (www.cellulardynamics.com)
hematopoietic stem cell-based therapy
collaborate to develop In Vitro Assays using
platform that also contains facilitating cells
human iPS cell-derived hepatocytes. The
derived from a donor. The platform supports
Hamner Institutes for Health Sciences today
the development of tolerance, or ‘bone marrow
announced a collaborative agreement with
chimerism,’ in transplant recipients, providing
Cellular Dynamics International (CDI) to
a better side-effect profile than current human
develop predictive in vitro screening assays for
hematopoietic stem cell transplantation
chemical, environmental, and pharmaceutical
protocols. Chimerism may eventually render
toxicology assessments that utilize CDI’s
the recipient tolerant to cell, tissue, or organ
human induced pluripotent stem (iPS) cell-
transplants from the same donor, thereby
derived hepatocytes.
enabling transplant patients to discontinue
immunosuppressive medications after building
stable immunological tolerance.
Next: Launching New Projects,
Results from a Phase II study in 15 kidney
Products, & Services (p. 37)
transplant recipients are encouraging,
with six patients fully withdrawn from
immunosuppression without loss of
engraftment, and a further two with planned
full withdrawal at 1 year. Currently, solid
organ transplant recipients must take
immunosuppressive drugs for life to prevent
rejection. This approach may also allow for
treatment of inherited metabolic diseases.
October 1, 2013
MiMedx Group, GA, USA (www.mimedx. com),
developer, manufacturer, and marketer of
patent-protected regenerative biomaterials
and bioimplants processed from human
amniotic membrane, has entered into a
distribution agreement with Medtronic, MN,
USA (www.medtronic.com) and SpinalGraft
Technologies, TN, USA, a wholly-owned
subsidiary of Medtronic.
Through the agreement, MiMedx will provide
its PURION® processed allograft products
to Medtronic to be marketed by SpinalGraft
Technologies for spinal applications. The
MiMedx allografts produced from the
company’s proprietary PURION Process for
amniotic membrane tissue can be stored at
room temperature for 5 years without the need
36
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
device, or approximately a quarter of the cost
of existing laser-assisted microdissecŧion
systems.
It has the additional capacity to collect cells
from tissues and cultures without affecting
their viability. This means the collected cells
can then be culŧured in the laboratory. Kuiqpick
can be attached to an inverted microscope to
dissect tissue slices at the cellular resolution
and collect individual cells from various cell
cultures.
Launching
March 1, 2013
Osiris Therapeutics, MD, USA
New Projects
(www.osiris.com) introduced a proprietary,
direct sales force for Grafix, a cellular repair
Products
matrix for serious wounds including diabetic
foot ulcers. In 2012, Osiris had received
& Services
transitional pass-through status from the
Center for Medicare & Medicaid Services
(MD, USA) with C-Codes being designated for
January 8, 2013
Grafix. Osiris medical affairs staff and a team
Thermo Fisher Scientific, MA, USA
of stem cell scientists will lend support for
(www.thermofisher.com) has expanded its
representatives.
suite of cryopreservation reagents with the
introduction of the Thermo Scienŧific HyClone
April 30, 2013 EMD
HyCryo™ and HyCryoSTEM™ cryopreservation
Millipore (www.emdmillipore.com), the
media. HyCryo™ is a medium for cryogenic
Life Science division of Merck, Germany
preservation and storage of standard cell lines,
(http://www.emdgroup.com), and Plasticell,
and HyCryoSTEM™ a medium for stem cell
UK (www.plasticell.co.uk) announced the
applications.
availability of OsteoMAX-XF™, the xeno-free
medium for the differentiation of human
January 28, 2013
mesenchymal stem cells into osteocytes.
Royan Stem Cell Technology, Iran
Mineralization can be detected in less than 1
(www.rsct.ir/en) has established an umbilical
week.
cord blood bank office in Erbil, Iraq.
April 30, 2013
January 29, 2013
RepliCel Life Sciences, BC, Canada
InSphero, Switzerland (www.insphero.com)
(www.replicel.com) started the clinical
launched a new service for testing embryonic
development of a new autologous cell
stem cell toxicity. The mouse embryonic stem
therapy for the treatment of a variety of
cell-based easyEST™ is now available as a
chronic tendon injuries. Preclinical research
service.
and published clinical Phase I data indicates
that the engraftment of collagen-producing
February 19, 2013
fibroblasts from the dermal sheath of a hair
follicle can repair microtears and promote the
NeuroInDx, CA, USA (www.neuroindx.com)
regeneration of damaged tendons associated
presented an innovative new cell and tissue
with chronic tendinosis. Phase I work in
microdissecŧion instrument Kuiqpick™.
humans, using fibroblast cells derived from
Kuiqpick costs less than US$30,000 per
adipose tissue, produced statistically significant
37
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
improvements in function and pain. RepliCel
formation and quantitating cell viability within
is planning a Phase II Achilles tendinosis trial
the spheroids in response to pharmacological
using a new source of cells, fibroblasts isolated
treatment. Uniform spheroid size and
from nonbulbar dermal sheath cells of a
physiology is determined through cell seeding,
hair follicle. This tendon technology, named
providing a robust and reproducible assay
RepliCel Tendon-01 (RCT-01), will be tested in
format for drug screening or pathway analysis.
approximately 90-120 subjects in a Phase II trial
anticipated to commence in late 2013.
August 1, 2013
ReNeuron, UK (www.reneuron.com), which
April 30, 2013
announced that they received regulatory
StemCell Technologies, BC, Canada
and ethical approval to commence a Phase I
(www.stemcell.com) has signed an agreement
clinical trial in the UK with its ReN009 stem cell
to license induced pluripotent stem cell
therapy program targeting the major unmet
technologies from iPS Academia Japan
medical need of critical limb ischemia, has
(www.ips-cell.net). This agreement will enable
been awarded two separate grants, totaling
StemCell Technologies to develop media for
US$1.86 million, from the UK Biomedical
optimization of cell reprogramming.
Catalyst to pursue further development of two
of its core stem cell therapy candidates.
May 20, 2013
Also following a further posiŧive assessment
Cord Blood America, NV, USA
from the independent data safety monitoring
(www.cordblood-america.com) launched a
board for the study, the final dose cohort
new service CordMatrix™ offering the storage
in the ongoing PISCES Phase I clinical trial
of mesenchymal stem cells from umbilical
with ReN001 in stroke therapy has now been
cords as both a stand-alone service and in
treated and the final patient dosed in the study
combination with the storage of umbilical cord
has been discharged from hospital.
blood, through its wholly owned subsidiary
CorCell Companies, NV, USA (www.corcell.
ReNeuron and the UK Center of Translational
com).
Excellence Catapult (http://ct.catapult.org.
uk/) signed an agreement to work together
June 5, 2013
on ReNeuron’s lead CTX stem cell line.
Catapult will contribute US$2.0 million into
Cellular Dynamics International, WI, USA
the collaboration, to be provided in the form
(www.cellulardynamics.com) company is
of expert knowledge, plus state-of-the-art
actively working on expanding its disease
laboratories, equipment, and services, while
model offering, currently working on additional
ReNeuron will also provide facilities, staff, and
disease models for neurodegenerative
relevant expertise.
disorders and drug-induced liver injury. Now it
offers through its MyCel® product line access
September 20, 2013
to a number of disease models, including
cardiomyopathies and arrhythmias, vision
STEMSOFT Software, BC, Canada
disorders, neurological disorders, and muscular
(www.stemsoft.com) released a new cord
dystrophies.
banking software STEMSOFT CORD. The
STEMSOFT CORD software is designed
June 25, 2013
to track all operational and manufacturing
details in one location while assisting with
AMSBio, UK (www.amsbio.com) has introduced
accreditation compliance, ensuring processing
a new range of 96-well format 3D Spheroid
standardization and increasing access to data.
Cell Proliferation/Viability Assays, providing
a new tool to allow cell-based assays to
September 26, 2013
be carried out in 3D. The assay offers an in-
vitro, standardized, 3D, high-content format
Cell Medica, UK (www.cellmedica.co.uk)
for inducing multicellular tumor spheroid
opened a commercial manufacturing facility
38
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
at the Max Delbruck Center for Molecular
claudication, a subset of peripheral artery
Medicine (www.mdc-berlin.de) within the
disease, to South Korea.
biotechnology park of Campus Berlin-Buch
in Germany. This state-of-the-art facility
Next: Accomplishments (p. 40)
for the cGMP production of cell and gene
therapies includes approximately 350 sq.
meters clean room space. Initial manufacturing
will focus on Cytovir™ CMV - an innovative
treatment that uses the immune cells of
a healthy donor to restore viral immunity
against cytomegalovirus infections in patients
who are immunocompromised following
allogeneic bone marrow hematopoietic stem
cell transplant. The commercial launch of this
product is planned in early 2014.
October 10, 2013
Scientists at Genea Biocells have achieved an
Australian first by producing human skeletal
muscle from stem cells - a breakthrough
expected to aid in the treatment of muscular
dystrophies.
October 15, 2013
Rainbow Scientific, CT, USA
(www.rainbowscientific.com) offers advanced
research products for human mesenchymal
stem cell and human embryonic stem cell
culture from Biological Industries, Israel
(www.bioind.com). The company claims that
these chemically-defined, non-animal origin
culture media can provide superior growth and
maintenance of mesenchymal stem cells and
human embryonic stem cell lines.
October 15, 2013
Life Technologies Corporation, CA, USA
(www.lifetechnologies.com) has extended
its collaborative agreement with Japanese
firm DNAVEC Corp. (www.dnavec.co.jp/
en) to launch the CytoTune™-iPS 2.0 Sendai
Reprogramming Kit, the next-generation
technology that enables an efficient method
for developing iPSC from human somatic cells.
November 13, 2013
Pluristem Therapeutics, Israel
(www.pluristem.com) receives regulatory
approval to extend Phase II Study of PLX-
PAD cells in the treatment of intermittent
39
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Accomplishments
January 17, 2013
were used in the first successful transplant of a
regenerated trachea in the USA. The recipient
Cellular Dynamics International, WI, USA
of the implant was a 2-year-old girl.
(www.cellulardynamics.com) announced that
it is producing human iPSC master cell banks
May 7, 2013
from five individual donors under cGMP,
enabling their possible use within a clinical
Researchers at Duke University, NC, USA
setting.
(www.duke.edu) combined Vista-Gen’s (CA,
USA) (www.vistagen.com) human stem cell-
January 24, 2013
derived heart cells with innovative tissue
engineering and cardiac electrophysiology
Genea Stem Cells, Australia
technologies to grow what is being called
(www.geneastemcells.com.au) announced that
a ‘heart patch,’ which mimics the natural
25 of its disease-specific human embryonic
functions of native human heart tissue .
stem cell lines have been placed on the US
NIH human stem cell registry. All of these cell
This heart patch technology is being
lines are genetically unmodified and have
developed for better understanding of the
been derived in compliance with internaŧional
biology critical to cardiac tissue engineering,
regulatory and ethical guidelines.
for applications in regenerative cell therapy for
heart disease, and as predictive in-vitro assays
Genea Stem Cells is planning to work with drug
for drug rescue and development.
developers globally to make disease-specific
cell lines for application from in-vitro research.
August 19, 2013
March 4, 2013
A University of California, Los Angeles, CA,
USA collaborative study demonstrated a
Cerapedics, CO, USA (www.cerapedics.com)
potential mechanism for converting research-
has announced that more than 10,000 patients
grade adult skin cells into clinical grade iPSCs
have been treated with its product i-FACTOR™
using two fibroblast lines from Fibrocell
worldwide since the product became available
Science, PA, USA (www.fibrocellscience.com)
outside the USA in late 2008. i-FACTOR
Peptide Enhanced Bone Graft incorporates
Next:
Cerapedics’ proprietary anorganic bone
mineral and synthetic small peptide (P-15™)
Capital Market Deals (p. 41)
technologies for use in a wide variety of spine,
trauma, and orthopedic surgical procedures.
i-FACTOR is not commercially available in the
USA, where it is, as an investigational device,
limited by federal law to investigational use
only.
April 30, 2013
Harvard Bioscience, MA, USA (HBIO) (www.
harvardbioscience.com) announced that the
InBreath tracheal scaffold and bioreactor
system manufactured by Harvard Apparatus
Regenerative Technology, Inc., MA, USA
(www.harvardapparatus.com), its wholly owned
regenerative medicine technology subsidiary,
40
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
July 31, 2013
Capital Market
Stratatech, WI, USA (www.stratatech.com)
has been awarded a contract valued at up
to US$47.2 million by the US Department
Deals
of Health and Human Service’s Biomedical
Advanced Research and Development
February 1, 2013
Authority. The contract is for the advanced
clinical and manufacturing development
Opexa Therapeutics, TX, USA
of StraŧaGraft skin tissue, the Company’s
(www. opexatherapeutics.com) granted
skin replacement product, as a medical
Merck Serono, Switzerland
countermeasure to treat patients with severe
(www.merckserono.com) an option
thermal burns.
for exclusive license to develop and
commercialize Tcelna™, an investigational
The total award will support the preclinical,
personalized autologous T-cell therapy for
clinical, regulatory, and technology
patients with multiple sclerosis. The potential
development activities needed to complete
first-in-class therapy has received the FDA’s
the FDA approval process for use of StrataGraft
Fast Track designation, and is now in an
skin tissue to treat thermal burn injury.
ongoing Phase IIb clinical trial in patients with
secondary progressive multiple sclerosis.
October 10, 2013
Osiris Therapeutics announced an agreement
March 21, 2013
with Mesoblast Limited for the sale of a
Coriell Institute, NJ, USA
culture-expanded mesenchymal stem cell
(http://ccr.coriell.org) was awarded about
platform. The transaction amounted to
US$10 million to set up and biobank storage
US$100M in initial consideration and milestone
of the iPS cell lines, of which Cellular
payments. Also, Osiris will receive royalty
Dynamics will be the primary subcontractor.
payments on sales of Prochymal and other
Coriell Institute will establish a biorepository
products using Osiris’s MSC technology.
with proven methods for managing sample
collection, tracking, and safe storage
December 11, 2013
capabilities for worldwide distribution of iPS
BrainStorm Cell Therapeutics, Israel
cells generated by Cellular Dynamics.
(www.brainstorm-cell.com) was awarded a
US$800,000 grant from Israel’s Office of the
March 21, 2013
Chief Scientist for the year 2013. The grant is
California Institute for Regenerative
intended to support BrainStorm’s research
Medicine, CA, USA (www.cirm.ca.gov) awarded
and development program for its proprietary
Cellular Dynamics Internaŧional, WI, USA
NurOwn™ technology for the propagation
(www.cellulardynamics.com) US$16 million to
and differentiation of autologous MSCs into
create three iPS cell lines for each of their 3000
neurotrophic factor-secreting cells.
healthy and diseased donors.
Also, BrainStrom has signed an agreement with
Tissue samples will be taken from patients
Octane Biotech, ON, Canada
suffering from Alzheimer’s disease, autism
(www.octaneco.com) to jointly develop a
spectrum disorders, neurodevelopmental
proprietary bioreactor for production of the
disabilities, cardiovascular diseases, liver
NurOwn stem cell therapy candidate.
diseases, and diseases of the eye or respiratory
diseases. Cellular Dynamics will generate the
iPS cell lines with the help of the episomal or
footprint-free reprogramming method they
developed.
41
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Industry Landscape
4
Denmark
1%
Netherlands
1%
1%
Sweden
Belgium
1%
8%
United Kingdom
Canada 2%
7%
Germany
France
4%
United States
2%
1%
52%
Spain
Israel
1%
China
2%
4%
Japan
India
1%
Singapore
2%
Malaysia 1%
Brazil
1%
Others
5%
Australia
2%
New Zealand
Chart 1:
United States
52%
United Kingdom
8%
Company Locations
Germany
7%
Company Locations
Japan
4%
In our database, we are presently
France
4%
tracking more than 500 companies.
China
2%
Looking at the geographic distribution
Switzerland
2%
of these companies, approximately
Australia
2%
52%, representing more than half of the
Canada
2%
organizations working in Regenerative
Singapore
2%
Medicine worldwide, are registered in
India
1%
the United States. Another 38 companies,
Israel
1%
representing 8%, are working from the
Sweden
1%
UK, and 33 companies, representing
Spain
1%
7%, are based in Germany. Despite the
Brazil
1%
size of biotech market in China, very
Malaysia
1%
little information is publicly available on
New Zealand
1%
regenerative medicine companies. The
Denmark
1%
following countries, represented in the
Netherlands
1%
“other” category, are characterized by the lowest ratios of
Belgium
1%
companies working towards RM or Stem Cell innovations.
Others
5%
Argentina, Cyprus, Ireland, the Republic of Korea (South
Korea), South Africa, Thailand, Poland, Slovenia, and South
Africa each have only one company qualifying for our
43
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
database.North Korea and Panama each have two companies in our database, while
Austria, Finland, and Italy have 3 each.
Chart 2: Organization Types
Looking at our companies based on their type of
Types of Organizations
organization and funding status, we find that the majority
are privately held, about 59.9%, with no stock offerings
as of yet, where another 28.9% are publicly held, with
private
60%
existing stock options. Of the remaining, 7.1% are classified
public
29%
as Academic, including University research centers
academic
7%
and Institutes, while non-profit organizations make up
non-profit
3%
2.8%. The non-profits consist of charity organizations,
hospital
1%
trial networks, interest groups, and foundations. We
track certain unique organizations within the category
“Hospitals,” and clinical stage research participant groups
make up 1.2%.
Companies Making Products for Specific Conditions
160
Cardiovascular disease s
Cancer
140
Blood diseases
120
Diabetes
100
Neurological diseases
Wounds
80
Reproductive system diseases
60
Ocular diseases
Gastrointestinal diseases
40
Urinary system disease s
20
Muscular and skeletal disorders
and injuries
Immunological diseases
0
Year of foundation
the 21st century, many of the companies in
Chart 3: Products for
our database have focused on developing
products to address specific conditions. The
Specific Conditions
majority of fully developed and marketable
products have come from specific areas, with
Since the introduction of Stem Cell and
treatments for musculoskeletal disorders,
Regenerative Medicine in the 1970s and into
cardiovascular diseases, wounds, cancer,
and neurological diseases achieving the best
44
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
measurable treatment results and
Regenerative Medicine Supply Lines, 1971 - 2012
the most success in the market.
180
Into the 21st century, our database
160
indicates that by 2012, a total
140
Autologous
of 141 Regenerative Medicine
120
Allogeneic
companies were working with an
100
Isogenic
interest in advanced therapies for
80
musculoskeletal disorders, while
60
Xenogeneic
only 28 companies are focusing on
40
treatments for reproductive system
20
diseases, indicating that this area of
0
interest may have significant room to
grow in coming years.
Year of foundation
both types of cells around the year 2000.
Chart 4:
Compared to the first two sub-fields, the
number of companies developing Xenogenic
Supply Lines
and Isogenic technologies represent similar,
though slightly less prevalent, portions of the
Since 1971, the industry has focused on
market prior to 2000, with a relatively smaller
developing specific types of engineered
boom since 2000, a “boom” that is relatively
cells for transplants and cellular therapy
large, nonetheless, when compared to pre-
procedures. Autologous and allogeneic
millenial levels.
cell supply lines represent (and
have always represented) similar
Stem Cell Companies Specialties, 1971 - 2012
presence in the market, and one
can clearly see a dramatic rise in the
250
number of companies developing
Embryonic stem
200
cells (ES)
150
Induced pluripotent
stem cells (iPSC)
100
Adult stem cells
Chart 5:
50
Company
0
Specialties,
1971-2012
Year of foundation
Of the wide range of specialized Regenerative
stem cell) technology is relatively new in
Medicine companies, many focus on various
comparison, and many older, more established
specific types of stem cells. Companies
companies have recently jumped on the iPSC
working with Adult stem cells saw an influx
bandwagon, transforming the specialization
of new companies starting in the mid-1990s,
into a comparatively booming industry moving
bringing about noticeable change in that
forward into the 21st century.
specific part of the industry. It is important to
recognize that the iPSC (induced pluripotent
45
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Product Trends, 1971 - 2012
300
Equipment
250
Reagents and
200
materials
150
Implants
100
Cell and tissue
sources
50
Information
0
Systems
Year of foundation
Chart 6:
Product Trends
In terms of new product development,
in Cell and Tissue Sources lagged
one observes that the development
behind the development of Equipment
of implants and information systems
and Reagents. In the 21st century,
do not appear to show a significant
though, the pace quickly picked up
rise compared to other technologies.
for Cell and Tissue products. From
For many organizations, Reagents and
our database records, a reported
Materials, Equipment, and Cell and
208 organizations focus on Cells and
Tissue sources appear to be the most
Tissue today, compared to the 108
attractive specialty fields at this time.
focusing on equipment. There appears
Many of the new organizations that
to be steady interest in the area of
came on board around the turn of the
Information Systems, though growth in
century did so to develop products in
this segment occurs at a slower pace
these areas.
compared to other areas.
It is imperative to state that the rise
46
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Company Interests, 1971 - 2012
300
250
200
private
150
public
100
academic
non-profit
50
0
Year of foundation
Chart 7:
Company Interests
The mid-1990s signified a
profit and academic organizations
clear increase in the number of
continue to rise steadily, though
both private and publicly held
at a slower pace than companies
companies. The dawn of the
engaged in the open market. It is
21st century brought about an
noteworthy to state that non-profits
exponentially faster rise in the
were the first type of organization
number of private companies,
on the scene, starting in 1971, while
along with a comparatively sized
private and public companies
rise in the number of public
came into the field starting in 1973
companies. The numbers of non-
and 1979, respectively.
47
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Company Distribution based on
Market Capitalization
Chart 8:
Less than $10 million
Market Cap
$10 million - $50 million
Today, the companies we track vary in Market
$50 million - $500 million
Capitalization from less than $10 million
$500 million - $2 billion
to larger than $2 billion, according to data
gathered from Yahoo finance. While some mid-
Larger than $2 billion
cap companies have a market capitalization
greater than $2 billion, at 26% of the market,
million to $50 million of share capitalization,
micro-cap companies make up 25% of the
and the remaining 10% of companies have
market, with market caps between $50
a market capitalization of $500 million to $2
million and $500 million. Another 20% of the
billion.
companies represent less than $10 million in
market capitalization. 19% hold between $10
Deals and Partnerships
Looking at deals and partnerships in
partnerships each.
regenerative medicine and stem cells, well
The main goals of these regenerative medicine
over 570 deals have been established since
and stem cell partnerships are of important
2009, based on Current Agreements’ Life
significance. Oncology ranks as the top area
Science Deals and Alliances Database.
of interest, with 159 inter-company deals. A
A noticeable development is huge interest
far second is cardiovascular treatment, with
from many high ranking pharmaceutical
74 partnerships, then hospital care, with 58
companies. This interest arises from
partnerships, followed by central nervous
anticipation that regenerative medicine and
system treatment with 57 partnerships, and
stem cell technology will produce viable,
metabolic diseases, with 49 partnerships.
mass market treatment solutions for many
Regenerative medicine and stem cell
conditions that were previously untreatable or
partnerships represent a sharply rising and
can be treated better with RM and stem cells.
stimulating development of new treatments
Pfizer leads the group of interested Big Pharma
and technology, where the industry as a whole
companies with 9 partnerships. They are
is coming together to produce compatible,
followed by Sanofi, which has 7 partnerships,
standardized treatment options for the mass
and GlaxoSmithKline and Roche, which have 3
market, and from this environment, even
Figure 1: Established deals in Regenerative Medicine and Stem since 2009
Source: Current Agreements, 2013
2009
109
2010
184
2011
104
2012
173
0
100
200
48
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Figure 2: Partnership deals among pharmaceutical companies in regenerative
medicine and stem cells since 2009
Source: Current Agreements, 2013
Number of Partnership Deals Announced
Pfizer
Novartis
Merck & Co.
Sanofi
Roche
GlaxoSmithKline
AstraZeneca
Johnson&Johnson
Abbott
Eli Lilly
Bristol-Myers Squibb
Teva
Amgen
Takeda
Boehringer Ingelheim
Bayer
Daiichi Sakyo
Novo Nordisk
Astellas
Gilead Sciences
Otsuka
Merck KG aA
Baxter
Mylan
Servier
Mitsubishi Tanabe
Celgene
CSL
Allergan
Forest
Dainippon Sumitomo
Shire
Menarini
Biogen Idec
Eisai
UCB
Watson
Purdue
Lundbeck
Warner Chilcott
Kyowa Hakko Kirin
Shionogi
Hospira
Valeant
Endo
Actavis
Grifols
Actelion
Galderma
Aspen
1
2
3
4
5
6
7
8
9
49
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
a small investment can
This industry, the next big
eventually yield large returns.
Characterized by lucrative
and profitable ventures,
thing in bioscience and
these areas of interest
provide opportunities for
industrial medicine for many
hefty rewards. The industry
presently rises above the
billion dollar level and is just
years into the future, can
now starting to produce new
products for an emerging
provide more than just a
market. Now is the time to
get involved, learn about, and
gain an understanding of the
financial reward, but also a
regenerative medicine and
stem cell industries.
path to improving the lives of
Today is the day to get
started.
many people.
Partnerships by Therapy Area
Anaesthetics 0
Figure 3: High ranking therapy areas for
regenerative medicine and stem cells
Hospital Care 58
partnerships since 2009
Breast 0
Source: Current Agreements, 2013
Cardiovascular 74
Central Nervous System 57
Dental 5
Dermatology 33
Gastrointestinal 5
Genetic Disorders 14
Genitourinary 5
Gynecology 0
Hematology 31
Immunology 25
Infectives 22
Metabolic 49
Musculoskeletal 36
Obstetrics 2
Oncology 159
Ophthalmics 33
Pediatrics 11
Psychiatry 13
Public Health 1
Respiratory 5
Sensory Organs 2
Sexual Health 0
50
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Trends
5
Regenerative Medicine, still an emerging
10 years, it is still uncertain how regenerative
field of specialized medicine, has enormous
medicine will develop in the future. Currently,
potential, spanning stem cell transplantation,
effective and safe regenerative therapies
cell reprogramming, synthetic organ
beyond bone marrow transplants remain
creation through tissue engineering, and
elusive and expensive.
nanotechnology. TechNavio’s analysts forecast
The ability to maintain sustainable investment
the Regenerative Medicine market in the US
in research, coupled with widespread ethical
to grow at a CAGR of 15.83 percent from 2012
concerns, could hamper the speed of progress
to 2016. One of the key factors contributing to
and implementation. In this section, we
this market growth is an increasing number of
cover several interesting trends and novel
degenerative diseases.
technological vectors defining the industry.
However, despite the progress of the past
$700.00
Funding
( Dollars In US $Milli ons )
$600.00
Human Embryonic Stem Cells
$500.00
Human Non-Embryo nic Stem
Cells
$400.00
Non-human Embryonic Stem
Cells
$300.00
Non-human Non-Embryonic
Stem Cells
$200.00
$100.00
$0.00
02
03
04
05
06
07
08
09
10
11
2012
Year
Chart: NIH Stem Cell Research Funding, FY 2002 - 2012 (Dollars in millions) Source:
http://stemcells.nih.gov/
Growing Stem Cell
Chart: Number of academic (“Non-profit”)
and commercial (“For profit”) entities
Research
sponsored by CIRM.
Source: http://www.cirm.ca.gov/
According to a new market report published by
Transparency Market Research (TMR 2013), the
market for stem cells was valued at USD $26.23
billion in 2011 and is expected to reach an estimated
For Profit
21
value of USD $119.51 billion in 2018, growing at
Non-Profit
49
a CAGR of 24.2% from 2012 to 2018. This market
growth is attributed to therapeutic research
activities led by government support worldwide, in
large response to the growing number of patients
52
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Total Number of Stem Cells Clinical
Trials, as of September 2013.
Source: http://www.ipscell.com/2013/09/maps-of-global-stem-cell-clinical-trial-trends/
34
266
1078
2848
381
175
43
53
28
18
43
59
133
around the globe with chronic diseases. In
Official data clearly shows the dynamic
many countries, the government is a major
increase of NIH government funding for
source of funding for the stem cell and
academic stem cell research since 2002.
regenerative medicine fields.
In turn, and in addition to academic
For instance, if we look at the National
organizations, CIRM also funds different
Institutes of Health (NIH) and the California
commercial entities allocated in California.
Institute for Regenerative Medicine (CIRM),
Those include companies like ViaCyte,
these two institutions fund by far the majority
Capricor, Stem Cells, Inc., Biotime, Cellular
of academic translational stem cell research
Dynamics International, and others. Since its
and regenerative medicine development in the
foundation in 2004, CIRM has given away more
US.
than $1.7bn worth of grants.
53
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Total Number of Mesenchymal Stem Cells
Clinical Trials, as of September 2013.
Source: http://www.ipscell.com/2013/09/maps-of-global-stem-cell-clinical-trial-trends/
6
7
84
71
114
31
5
14
11
9
9
Another illustration of this trend is the growing
European Union, China, and Canada.
number of stem cell clinical trials.
Even more astonishing is the dynamic of MSC-
According to the Knoepfler Lab Stem Cell
associated clinical trials. The total number
Blog (URL Ref. 13), the number of clinical trials
of MSC trials increased by 26% during this
associated with stem cells is growing very
time, from 281 to 354. This increase suggests
rapidly. In the study, Knoepfler Lab tracked all
that the rate of growth for MSC research is
stem cell-based clinical trials registered from
substantially faster than that of the overall
December 2012 to September 2013. It has
stem cell research being conducted. In terms
been shown that in these 10 months, the total
of numbers, the global leader of MSC clinical
number of clinical trials increased by 10.6%
trials is China, followed by the European Union
from 4,316 to 4,775. Most of the clinical trials
and the United States.
were registered in the US, followed by the
54
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Currently, there are around 20 companies
developing and commercializing POC cell
therapies. In 2007, one of the frontrunners
in the field of POC cell therapy, Cytori
Therapeutics, entered the POC market and
presented its FDA-approved Autologous
Fat Transfer (AFT) System. In July 2013,
ThermoGenesis and TotipotentRx (TotiRx)
Point-Of-Care Cell
merged in an all-stock deal to create one
public company, Cesca Therapeutics. With
Therapy
the combined clinically-validated cell therapy
protocols and cell therapy kits of TotiRx and
In Glossary: ADRC - adipose-derived
the cell-processing devices of ThermoGenesis,
regenerative cells
Cesca Therapeutics might become one the
strongest players in the POC cell therapy
Point-of-care (POC) cell therapy is a medical
market. In August 2013, Cytori Therapeutics
procedure where the patient is treated with
received notice from the Australian
tissues or cells produced from cells native
Therapeutic Goods Administration (TGA)
to the patient’s body. The therapy consists of
that the Celution System was approved for
several steps, including collection of native
commercial use for autologous re-implantation
cells, processing, and administering new cell
and re-infusion of a patient’s own ADRCs. This
structures. The procedure is comparatively
approval enables physicians to treat critical
fast and can take from 1 to 30 hours. POC
unmet medical needs with point-of-care cell
cell therapy is already being used for the
therapies and to conduct important clinical
treatment of multiple conditions covering soft
research in promising areas of therapeutics.
tissue disorders, neurological diseases, dermal
wounds, and spine injuries.
Using the patient’s own cells via POC cell
therapy represents a far safer and cheaper
approach than allogeneic transplantation.
Another advantage of POC cell therapy is the
possibility of creating custom combinations of
different cell types to treat complex diseases.
Nevertheless, there are a number of issues
3D-Bioprinting
doctors must take into account, such as the
source and dose of the cells, a patient’s age
3D-Bioprinting is a technology derived from
and health status, possible side effects of
additive manufacturing activities that consist
device implants, and environmental factors
of printing, layer by layer in 3D, the biologically
effecting new tissues. Despite the complexity
relevant materials (such as cells, tissues,
of manufacturing and logistics, POC cell
or biodegradable biomaterials) that will
therapy has far fewer issues with quality
accomplish one or more biological functions.
control and approval than other conventional
This technology covers a wide range of
cell therapies requiring GMP processing and
applications, from drug discovery and assays
obligatory IND clinical trials. Of course, certain
to in vitro diagnostics, cell therapy, and tissue
companies work around the presently loose
engineering, as well as the production of
FDA regulations and market their devices
biomolecules. This year, we have already
without any FDA clearance whatsoever. The
witnessed many cutting-edge developments
lack of strict FDA regulations, combined
and big steps in terms of new 3D printing
with limited clinical trial data and treatment
innovations.
protocols still being developed, represent
issues for the future of POC cell therapy.
In September 2012, At the University of
55
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Missouri, Columbia, researchers have
University using a biomaterial 3D printer called
3D-printed viable, functional blood vessels and
“Regenovo” successfully printed out small-
sheets of beating heart muscle.
scaled human body parts, like an ear and a
nose (URL Ref. 17).
In February 2013, Dr. Will Shu and his
colleagues at Heriot-Watt’s Biomedical
The aforementioned organizations engaged
Microengineering Group were the first to print
in 3D bioprinting currently focus solely on the
more delicate embryonic cell cultures, which
research, but there are several commercial
have an ability to replicate indefinitely and
companies moving forward with research and
differentiate into almost any cell type in the
development, hoping to extract some profit in
human body (URL Ref. 14).
the near future. The world’s first commercial
bioprinter, the NovoGen MMX Bioprinter, was
In February 2013, Larry Bonassar, Cornell
put on the market in 2009 by a company
Associate Professor of Mechanical Engineering,
called Organovo. Organovo uses bioink made
and his research team developed a 3D printing
up of various human cells and places them
method to produce a precisely-modeled
in a precise manner using its NovoGen MMX
replacement human ear. (URL Ref. 15)In July
Bioprinter into microplates or other form
2013, scientists at Wake Forest University’s
factors. Because these cells are placed in a
Military Research Center developed a method
certain architecture and are fed with nutrients,
to 3D print new skin cells directly onto burn
they begin to signal to each other to behave
wounds. (URL Ref. 16)
naturally, catalyzing the formation of tissue.
China is also keeping the pace. In August
Organovo’s competitor in the bioprinting
2013, researchers at Hangzhou-based Dianzi
3D Printed Parts Market Size in US $ Millions
$9,000m
$8,000m
$7,000m
Aerospace
$6,000m
Medical
$5,000m
Automotive
$4,000m
Electronics
$3,000m
Consumer
$2,000m
$1,000m
12
13
14
15
16
17
18
19
202
12
22
32
4
2025
Year
56
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
market is TeVido BioDevices. TeVido
$1.9 billion share of the market (rising from a
BioDevices is an early-stage life science and
modest $11 million in 2012) will come from 3D
biotech company using 3D bioprinting of live
printed medical devices and orthopedic parts.
cells to build custom implants and grafts for
Basically, biotech firms in this emerging field
breast cancer-effected tissue reconstruction.
are not yet profitable, as they still have very
In 2013, nearly 300,000 women in the US
low revenue coupled with high R&D expenses.
will be diagnosed with breast cancer, with
For instance, Organovo’s revenues doubled
50-60% of them choosing a lumpectomy as
to $1.2m between 2010 and 2012, but losses
part of the treatment. Longer term, TeVido’s
increased nearly eight-fold to $9.3m in the
solution for lumpectomies could expand to
same time period (URL Ref. 18).
the broader and more lucrative market for
breast augmentation, which is estimated at
All of the companies engaged in the 3D
$10 Billion in the U.S. According to TeVido, this
bioprinting field are facing the same regulatory
application will take seven more years of R&D
difficulties. At the moment, their services will
and approximately $40million of funding.
only be available for drug and other medical
research. In the short term, they can increase
So what is the global 3D printing picture at the
their revenue by providing products to aid
moment? According to a report from Boston-
in academic and pharmaceutical research.
based Lux Research, the overall 3D printing
It may be years before tissue-engineered
market had a $777 million base in 2012, with
products are actually available and approved
3D printed prototype parts in aerospace and
for widespread application to the human body.
automotive applications totaling $315 million
Yet, the companies continue their research to
and $428 million, respectively, accounting for
create valuable patents. At the moment, the
more than 95% of aggregate sales. The market
main source of dividends for investors in this
for 3D printing is expected to grow to $8.4bn
specialized field are potential buyouts from
by 2025. Bioprinting’s contribution will be
larger pharma companies.
negligible, and most of the medical industry’s
Company
Ticker
Number of drugs
R&D Spending Per
Total R&D Spending
approved
Drug ($Mil)
1997-2011 ($Mil)
AstraZeneca
AZN
5
11790.93
58955
GlaxoSmithKline
GSK
10
8170.81
81708
Sanofi
SNY
8
7909.26
63274
Roche Holding AG
RHHBY
11
7803.77
85841
Pfizer PFE Inc.
PFE
14
7727.03
108178
Johnson & Johnson
JNJ
15
5885.65
88285
Eli Lilly & Co.
LLY
11
4577.04
50347
Abbott Laboratories
ABT
8
4496.21
35970
Merck & Co Inc
MRK
16
4209.99
67360
Bristol-Myers Squibb Co.
BMY
11
4152.26
45675
Novartis AG
NVS
21
3983.13
83646
Amgen Inc.
AMGN
9
3692.14
33229
Table. Research Spending Per New Drug. Source: http://www.forbes.com
57
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
medicine applications. The first results from
several studies are expected to be published
after the second half of next year, after which
a path to commercial application can be
formulated.
Organovo is also working on the development
of tissue-engineered therapies to replace
Why Should
damaged or diseased tissue, but creating a
fully functional organ is a very difficult task for
“Big Pharma” Be
researchers at present, and it may take years
before the ability to produce one becomes a
Interested?
reality. Once it is created, it may require up to
a decade to complete the necessary trials to
According to a Forbes’s article by Matthew
release it for medical application.
Herper (URL Ref. 19), the top 12 pharmaceutical
companies spent $802.5 billion on research
and development between 1997 and 2011 on
their way to 139 drug approvals. This means
that in average, a single company spent an
astounding $5.77 billion per each approved
Medical Tourism
drug. Several perspective in silico methods
for drug discovery have even been proposed
‘Medical Tourism’ refers to the practice by
(Zhavoronkov 2014).
patients of travelling to a different country for
an urgent or elective medical procedure that
One of the biggest problems during drug
is either not approved or too costly in their
discovery is accurately assessing the drug’s
home country. The practice is fast becoming
toxicity to human cells, particularly liver toxicity.
a worldwide, multibillion dollar industry.
Approximately 25% of all drugs that were
According to United Nations statistics, the
withdrawn from the market or failed a phase 3
median age of the world’s population will be
trial between 1990 and 2010 were yanked due
growing over the next 50 years in all major
to liver toxicities (URL Ref. 20). 3D bioprinting
regions of the world. Biomedical progress has
companies can help Big Pharma companies
already been suggested as one of the future
increase their efficiency by more accurately
key economical factors for these age groups
predicting liver toxicities.
(Zhavoronkov 2013). And, in turn, the increase
Earlier this year, Organovo published data on
of the median age of population will bring
its 3D bioprinted liver model and found that
an increasing flow of potential customers
the liver tissue lasts much longer than 2D
interested in medical tourism.
cell cultures. And even before the data was
Medical tourism is an emerging global
published, Organovo established agreements
industry, with a range of key stakeholders
with Pfizer and United Therapeutics to use its
and commercial interests including brokers,
technology for drug discovery.
healthcare providers, insurance providers,
In January 2013, the company signed an
website providers, networking providers,
agreement with Knight Cancer Institute at
and media services. According to a new
Oregon Health & Science University to develop
market report published by Transparency
more clinically predictive in vitro 3D cancer
Market Research, “Medical Tourism Market
models to advance discovery of novel cancer
(India, Thailand,Singapore, Malaysia, Mexico,
therapeutics, along with signaling pathway
Brazil, Taiwan, Turkey, South Korea, Costa
analysis (Buzdin 2014) - these models could
Rica, Poland, Dubai and Philippines) - Global
be useful for researching new oncology
Industry Analysis, Size, Share, Growth, Trends
compounds and developing personalized
and Forecast, 2013 - 2019,” the global medical
58
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
tourism market was valued at USD $10.5 billion
appeared option of personalized science
in 2012 and is estimated to reach a market
(Zhavoronkov 2014).
valuation of USD $32.5 billion in 2019 at a CAGR
Some countries have less strict regulations
of 17.9% from 2013 to 2019.
concerning drugs and medical innovation,
The rise in healthcare costs in developed
and stem cell therapy remains uncontrolled
countries coupled with the availability of
(or even encouraged) in these parts of the
high quality medical services at a low cost in
world. According to the National Center
developing countries have given a boost to
for Biotechnology Information, over 700
the medical tourism industry. These medical
companies and clinics around the world offer
services range from elective procedures such
stem cell therapy services. Many experts, as
as cosmetic surgeries to complicated surgeries
well as the International Society of Stem Cell
such as cardiac procedures, orthopedics,
Research and the FDA, discourage people
neurosurgery, and others. Significant growth in
from traveling overseas for such treatments,
this industry is due to economic developments
saying the treatments are unsafe and
in developing countries that in turn has led
unproven. Patients and physicians ought to
to the growth in the medical industry and
distinguish between clinically-proven stem cell
the quality of medical services. Biomedical
treatment, non-approved stem cell therapy in
progress has been already suggested as
competent clinics, and fraudulent stem cell
one of the future key economical factors
therapy with no scientific basis whatsoever.
(Zhavoronkov 2012).
In August 2013, ISCT published Patient Advisory
The rise in healthcare expenditures in
for Stem Cell Therapy and Medical Tourism.
developed countries coupled with a growing
In this document, ISCT emphasized the key
elderly population has also contributed to
points that physicians, patients, and family
the growth of medical tourism around the
members should carefully consider before
globe. The recent economic crisis in the U.S.
starting any stem cell-based treatment. ISCT
has increased the number of the uninsured
is the only group focused on pre-clinical and
population, consequently further triggering the
translational aspects of developing cell therapy
growth of this market.
products. As such, ISCT helps academic,
government, and biotech/pharma sectors
Among this giant industry, there are a small
transform research into practice and product.
number of regenerative medicine solutions.
In September 2013, the International Society for
So-called “stem cell tourism” has already
Stem Cell Research (ISSCR) has urged medical
become an emerging trend, at the same time
licensing bodies, legal authorities, patient
raising quite a bit of concern. Due to the slow
advocacy organizations, clinics, and physicians
drug approval procedures in the U.S. and the
to exercise their power in discouraging
growing number of already ill and desperate
commercial treatments of unproven stem cell
people, patients often go to other countries
therapies outside of clinical trials.
looking for non-approved stem cell treatment.
Some people are even exploring the newly
59
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Clinical Trials
Here, we overview
international clinical
trial databases via
the WHO Search
Portal. We have
tracked trials in
cell therapy and
tissue engineering
registered from
Jan.1, 2013 to
Dec.31, 2013.
generative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Cell Therapy
Clinical Trials
We tracked trials by following the search
Sponsorship
terms: “cell therapy” and “stem cells.” At this
stage, we have excluded trials related to tissue
engineering, gene therapy, growth factor
Cell Therapy: Sponsorship
therapy, and platelet-rich plasma use. We will
describe these aspects of the regenerative
Academic
153
medicine field in the next stages of our
Commercial
31
research and publications.
We have also excluded research efforts
All trials were divided into 2 categories -
related to the use of stem cells for diagnostic
“Academic” or “Commercial.” “Academic” trials
purposes, like stem cell phenotyping for
are supported by non-profit organizations, and
cancer research, as well as data related to
“Commercial” trials are sponsored by profit-
supportive manipulations around stem therapy,
seeking agencies.
like antibiotic indications during allogeneic
stem therapy for immunosuppressive
conditions and the complications related to the
Demographics
therapy.
France
3
We have included all trials assessing the
Russia
3
use of stem hematopoietic and other blood
UK
3
cells in blood malignances. We took data
Brazil
4
about trial ID, country of origin, phase of
Italy
5
research, indication, cell type, donor type,
Australia
5
type of sponsorship, company-sponsor name,
and product identification from each trial’s
Germany
5
description. To date, we have tracked 184 trials
Iran
6
for the calendar year 2013.
Spain
9
Others
12
South Korea
13
Database
India
16
China
22
Representation
Cell Therapy: Countries
Japan
27
USA
51
Cell Therapy: Databases
“Other Countries” include Sweden, Switzerland,
South Korea
KCT
1
Poland, Mexico, Taiwan, Panama, and Egypt.
Deutch
DRK
2
The number of trials registered in these
India
CTRI
2
countries during 2013 was smaller, registering
Iran
IRCT
4
at 1 or 2 per country.
International
ISRCTN
5
Australia
ACTRN
5
China
ChiCTR
8
Europe
EUCTR
10
Japan
JPRN
25
USA
NCT
122
61
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
34+ progenitors.
“Adult Immune” includes cytokine-induced
killer cells, T-lymphocytes, NK-cells, and
Cell Types
dendritic cell vaccines.
“Bone-Marrow Derived Stem Cells” is
related to the mononuclear part of bone-
ES+fetal
3
marrow derived stem cells and separate
Neuronal Precursor
2
fractions of it like mesenchymal SC,
Cardiac Precursor
3
endothelium, and blood progenitors.
iPSC
3
Other Adult
8
Cell Donor Type
Cord Blood SC
12
ADSC
15
Hematopoietic
31
Adult Immune
44
Bone Marrow
67
Derived SC
Cell Therapy: Cell Types
Allogeneic
75
Autologous
119
The number of cell types mentioned is 188,
because some trials act on an assortment of
Cell Therapy: Source of Donor Cells
cell types, rather than a single cell type. For
example, the cell type category “MSC Cells”
can include bone marrow, adipose tissue, and
The number of cell types we are mentioning is
cord blood. Our classification system is partly
194, because 5 trials assessed the use of both
tissue-oriented, because hematopoietic cells
autologous and allogeneic cells.
can also be derived from the above-mentioned
These diagrams represent the distribution of
tissues and organs, and cellular therapy can be
autologous and allogeneic donorship between
based on many types of stem and progenitor
commercial and academic trials.
cells derived from a single source.
We have subdivided the cell types used for
cell therapy into the following categories:
Distribution of Donor Type
ES and fetal”: fetal fibroblasts, fetal neuronal
in Academic Trials
cells, placenta-derived cells.
Academic Allogeneic
60
“iPSC”: induced Pluripotent Stem Cells.
Academic Autologous
103
“Adult, Adult Stem, and Progenitor Cells”:
neuronal (including adult olfactory mucosa),
cardiac (including cardiosphere-derived
cells), pancreatic progenitors cells,
chondrocytes, osteoblasts.
“Adipose-Derived Stem Cells”: cells derived
from adipose tissue, also called SVF, or
Distribution of Donor Type
in Commercial Trials
Stromal Vascular Fraction.
Commercial
16
“Cord Blood Cells”: includes all types of
Allogeneic
cells derived from umbilical cord blood.
Commercial
15
Autologous
“Hematopoietic”: mobilised peripheral blood
stem cells, including adult endothelial CD
62
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Companies And Products
Acting In Cellular Therapy
Name of Company
Product(s)
Indication
Phase
Country
Angioblast Systems
Stro3 - allogeneic bone marrow derived MSC
Acute Myocardial Infarction
Phase 2
USA
Facial fat grafting, cosmetic
Antria
Autologous adipose-derived MSC
Phase 1
USA
surgery
Dry Age-related macular
Bioheart, Inc
Autologous adipose-derived MSC
Phase 1/2
USA
degeneration
Bone Therapeutics S.A.
PREOB® - autologous osteoblastic cell product
Fractures, osteonecrosis
Phase 2b/3
Netherlands
MSC-NTF Cells technology:
technology for the propagation and
Brainstorm-Cell
differentiation of autologous Mesenchymal Stem
Amyotrophic Lateral Sclerosis
Phase 2
USA
Therapeutics
Cells (MSCs) into NeuroTrophic Factor (NTF)-
secreting cells
Autologous Dendritic Cell-Tumor Cell
Stage IV Melanoma
California Stem Cell, Inc.
Phase 3
USA
Immunotherapy
Stage III Melanoma
PDA002 - allogeneic human placenta-derived
Peripheral Arterial Disease
Celgene Corporation
Phase 1
USA
cells
Diabetic Foot
Neurodegenerative Diseases
Osteoarthritis
Erectile Dysfunction
Cell Surgical Network Inc
Autologous adipose-derived MSC
Phase 1
USA
Autoimmune Diseases
Cardiomyopathies
Emphysema
Cellular Biomedicine
Autologous adipose-derived MSC
Osteoarthritis
Phase 1/2
China
Group Ltd.
Citospin
MSV® - Allogeneic bone marrow derived MSC
Degenerative disc disease
Phase 2
Spain
Dong-A Pharmaceutical
Collaborator for Medipost Co Ltd CARTISTEM®
Republic of Korea
Co., Ltd.
trial.
FCB-PHARMICELL CO.
Autologous bone marrow derived MSC
Alcoholic liver cirrhosis
Phase 2
USA
Fondren Orthopedic
Microfracture surgery, cartilage
Autologous adipose-derived MSC
Phase 1/2
USA
Group L.L.P.
regeneration
InGeneron’s Transpose RT™ System is a system
for the preparation of autologous regenerative
InGeneron, Inc.
USA
cells from human lipoaspirate. Collaborator for
Fondren Orthopedic Group L.L.P’s trial.
Hematological Malignancies
NiCord® - allogeneic umbilical cord blood-
Acute Lymphoblastic Leukemia
derived Ex Vivo Expanded Stem and Progenitor
(ALL)
Gamida Cell ltd
Phase 1/2
Israel
Cells
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome
(MDS)
PNEUMOSTEM®
Phase 2
Bronchopulmonary Dysplasia
(PNEUMOSTEM)
Medipost Co Ltd
CARTISTEM®
Degenerative Osteoarthritis
Republic of Korea
Phase 3
Both are allogeneic umbilical cord blood derived
Defect of Articular Cartilage
(CARTISTEM)
MSC.
Rheumatoid arthritis
Mesoblast, Ltd.
Allogeneic bone marrow derived MSC
Phase 1/2
USA
Diabetic nephropathy
Miltenyl biotech
CliniMACS® Cytokine Capture System
Adenovirus infection
Phase 1/2
Switzerland
The CliniMACS® Cytokine Capture System
(IFN-gamma) - Product Line is comprised of the
CliniMACS IFN-gamma Catchmatrix Reagent,
consisting of CD45 antibodies conjugated to IFN-
gamma specific antibodies, and the CliniMACS
IFN-gamma Enrichment Reagent.
Neuralstem Inc.
Human spinal cord stem cells
Spinal Cord Injury
Phase 1
USA
RNL Bio Company Ltd.
Autologous Adipose Tissue derived MSC
Spinal Cord Injury
Phase1/2
Republic of Korea
Stemedica Cell
Allogeneic Mesenchymal Bone Marrow-derived
Intrinsic Aging of Skin
Phase 1/2
USA
Technologies, Inc.
MSC
Chronic Effect of Ultraviolet
Phase 2 (STEMI)
Radiation on Normal Skin
(Photo-aging)
Dermatologic Disorders, ST
Segment Elevation Myocardial
Infarction (STEMI)
63
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
SYZ Cell Therapies Co
MASCT That Expresses Multiple Antigens Specific
Treatment of hepatocellular
Phase 2
China
Cellular Therapy, Autologous Immune Cytotoxic
carcinoma
of T-lymphocytes(CTL) Induced by Dendritic
Cell(DC) Loaded With Multiple Antigens
Tianhe Stem Cell
Stem Cell Educator therapy: cord-blood stem
Diabetes mellitus type 1
Phase 1/2
China
Biotechnologies, Inc
cells that can control autoimmune responses by
altering Tregs and human islet b cell-specific T
cell clones
Translational Biosciences
Autologous Adipose Tissue derived MSC
Rheumatoid Arthritis
Phase 1/2
Panama
*Repeated companies are not included.
“Musculosceletal Disorders”: fractures,
injuries, chondropathies, arthropathies,
osteonecrosis, Duchenne’s muscular
Indications
dystrophy,
“Diabetes”: conditions related to type 1 and
Reproductive System
3
Diseases
type 2 diabetes.
Aesthetic Medicine
2
Aging
3
“Immune Disorders”: graft-versus-
Ophthalmology
5
host disease, autoimmune diseases
like rheumatoid arthritis, scleroderma,
Diabetes
6
congenital immune deficiency, GATA2-
Respiratory
7
deficiency, Crohn’s disease, and other
Unhealing Wounds
7
inflammatory bowel disease.
Other
12
Cardiovascular
18
“Ophthalmology”: glaucoma, age-related
Immune Disorders
19
macular degeneration, retinitis pigmentosa,
Musculoskeletal Disorders
19
optic nerve disease.
Cell Therapy: Indications
Neurological Diseases
25
“Respiratory Disorders”: bronchopleural
Cancer
58
fistula, idiopathic pulmonary fibrosis,
acute respiratory-distress syndrome,
“Neurological Disorders”: spinal cord and
bronchopulmonary dysplasia, pulmonary
brain injury, Parkinson’s disease, stroke,
emphysema.
cerebellar ataxia, chronic paraplegia, mental
retardation, amyotrophic lateral sclerosis,
“Reproductive System Diseases”:
multiple sclerosis, muscular atrophy type IV,
Ashermann syndrome (adhesions inside
Huntington’s Chorea.
the womb after childbirth) and premature
ovarian failure, azoospermia.
“Cardiovascular Disorders” are related
“Aging”: cutaneous photoaging, skin aging.
to acute myocardial infarction, other
ischemic disorders excluding ischemic
“Other” included fecal incontinence, liver
limbs disease (because the main problem
cirrhosis, chronic renal failure, adenovirus
for these patients is unhealing ulcers, and
infection, amyloidosis, sickle cell disease,
this is a cause for intervention), vascular
adenovirus infection.
insufficiency in terms of angiogenesis
“Aestetic Medicine”: cosmetic surgery, skin
evaluation, defective development
aging.
like hypoplasia of left ventricle, arterial
hypertension, atherosclerotic stenosis of
arteries, dilated cardiomyopathy.
64
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Phases Of Clinical
Trials
Database
Cell Therapy:
Representation
Phases of Clinical Trials
Phase 3
7
Phase 4
7
Dutch
NTR
2
Phase 2
42
International
ISRCTN
2
Phase 1
45
Australia
ACTRN
4
Phase 1/2
83
Dutch
DRK
2
India
CTRI
3
Iran
IRCT
3
Phase 1/2 trials combine a Phase 1 and a
Japan
JPRN
4
Phase 2 trial of the same treatment into a
Tissue Engineering:
China
ChiCTR
3
single protocol. First, the Phase 1 part of the
Databases
USA
NCT
29
trial determines the Maximum Tolerable Dose
(MTD), and further evaluation of safety and/or
efficacy can be done in the Phase 2 portion of
the study.
Tissue Engineering:
Demography
Tissue
Australia
5
Brazil
2
Engineering
India
3
Netherlands
3
Clinical Trials
South Korea
2
Germany
3
We tracked Tissue Engineering trials by
Italy
3
following the search terms “tissue engineering,
France
5
scaffold, matrix, transplant, and implant.”
Japan
5
We have excluded from our search results
Iran
5
the data related to synthetic implants such as
Tissue Engineering: Countries
Others
9
metal and silicone implants, allogeneic organ
USA
13
transplants like kidney or liver transplantation,
xenogenic valves for cardiological needs, and
The category “Other” includes Belgium,
drug-eluting vascular stents.
Switzerland, Azerbaijan, Hong Kong, Singapore,
Denmark, Israel, and Spain with 1 tissue
We took data about trial ID, country, phase,
engineering trial registered in 2013. The
type of replaced tissue, presence of cellular
number of countries tracked is 58, because
and acellular(scaffold) components in grafts,
some trials are international.
indication, donor type, type of sponsorship,
name of company-sponsor, and product from
each trial’s description. The total number of
trials tracked is 52.
65
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
1.
transplantation of pancreatic islets for
treatment of diabetes mellitus, type 1 and
benign pancreatic neoplasms (after partial
pancreatectomy);
Tissue Engineering:
2.
autologous transplantation of cultured
fibroblast on amniotic membrane in patients
Sponsorship
with epidermolysis bullosa;
3.
transplantation of tissue-engineered
autologous oral mucosal epithelial cell
Tissue Engineering: Sponsors
sheets in preventing formation of strictures
after endoscopic submucosal dissection for
Commercial
23
esophageal cancer;
Academic
29
4.
transplantation of tissue-engineered
autologous skin sheets in wound healing or
burn treatment:
All trials were divided into 2 categories -
“Academic” or “Commercial.” “Academic” trials
5.
treatment of nonunion of long bone
are supported by non-profit organizations, and
fracture using mononuclear stem cells from
“Commercial” trials are sponsored by profit-
the iliac wing within a 3-D tissue engineered
seeking agencies..
scaffold;
Tissue Engineering:
Tissue Engineering:
Tissue Type
Connective
22
Materials
Epithelial
14
Other
16
Tissue Engineering: Materials
The category “connective tissue” includes
Cellular
8
material for bone, cartilage (intervertebral
Acellular (only scaffold)
44
disks), tendon, and loose connective tissue
reconstruction. Products for recovery and
remodeling of mucosal, conjunctival, and also
endocrine epithelium are observed under the
term “epithelial.” “Other” is a group of materials
“Acellular” includes tissue enjineering trials not
like vascular stents and hemostatic materials.
involving any cells. “Cellular” clinical trials could
investigate the use of cells, cells and scafford,
Tissue Engineering:
or tissues in tissue engineering. Acellular
materials are more abundant between tissue
Source Of Donor
engineering products. Investigation of acellular
matrixes for needs of dental, reconstructive,
Material
and traumatic surgery is frequent between
non-commercial and industrial trials.
Interestingly, all commercial trials are related
Tissue engineering:
source of donor material
to investigation of allogeneic or xenegeneic
acellular matrixes and scaffolds in different
Autologous
9
approaches.
Xenogenic
27
Allogeneic
16
Trials which use cellular components
include:
66
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Companies And Products Acting
In Tissue Engineering
Name of company
Product(s)
Indication
Phase
Country
Abbott Vascular
Absorb™ BVS, Bioresorbable
Coronary Artery Disease,
Phase 1/2
Japan, Netherlands
Vascular drug-eluting Scaffold
myocardial ischaemia
Phase 1
Allergan Medical
SERI® xenogenic surgical scaffold
breast cancer, reconstruction
Phase 4
Israel
surgery
Phase 1
USA
Biosensors International
BioMatrix™ xenogenic
Coronary artery disease
Phase 1/2
India
Ltd
biodegradable polymer arterial
stents
Celxcel Pty Ltd
CardioCel® allogeneic acellular
congenital heart disease
Phase 1/2
Australia
tissue matrix
Elixir Medical Corporation
DESolve® Novolimus eluting
Coronary artery disease
Phase 4
USA
bioresorbable coronary scaffold
Geistlich Pharma AG
Geistlich Bio-Oss® - allogeneic
Dental Surgery
Phase 4
Switzerland
bone mineral matrix
Kensey Nash Corporation
Meso BioMatrix Device, allogeneic
breast cancer, reconstruction
Phase 1/2
USA
acellular matrix
surgery
Keystone dental
DynaMatrix® allogeneic non-
Dental Surgery
Phase 1/2
USA
biodegradable acellular matrix
LifeCell
Device: Strattice™ allogeneic
breast cancer, reconstruction
Phase 1/2
Italy
acellular dermal tissue Matrix
surgery
Luitpold Pharmaceuticals
As collaborator
Dental Surgery
Phase 4
USA
Osteohealth®
Mucograft® Allogeneic Acellular
Dental Surgery
Phase 2
USA
Collagen Matrix
EQUIMATRIX® - allogeneic bone
Phase 4
mineral matrix
Otr3
CACICOL20®, single-dose
Corneal ulcers and dystrophy
Phase 2
France
eye drops for corneal healing
prescribed for chronic corneal
lesions.
Perio Health
Xenogenic Collagen Matrix
Dental Surgery
Phase 2
USA
Professionals™
PolyNovoBiomaterials
NovoSorbTM Biodegradable
Burn treatment
Phase 1
Australia
Pty Ltd
Temporising Matrix (BTM)
TEI Biosciences Inc
SurgiMend, allogeneic acellular
breast cancer, reconstruction
Phase 1/2
USA, UK
dermal biodegradable matrix
surgery
Tornier, Inc
BioFiber™ Absorbable Biologic
Cuff, Rotator
Phase 4
France, USA
Scaffold for Soft Tissue Repair and
Reinforcement
Zimmer Dental Inc
Puros - allogeneic bone mineral
Dental Surgery
Phase 4
USA
matrix
67
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
“Ophthalmology”: pterigium, open-angled
Indications
glaucoma, cataract, corneal traums.
Tissue engineering:
“Cardiovascular Diseases”: ischemic heart
Wound Healing
5
Indications
disease, IM treatment, congenital heart
Diabetes
2
disease.
Hemostasis
2
Other
3
“Stomatology”: dental surgery is the most
Musculoskeletal Disorders
6
frequent indication for tissue-engineered
Cosmetic Surgery
6
products. Implants and scaffolds are
Ophthalmology
7
used for soft tissue replacement, sinus
Cardiovascular Diseases
10
augmentation, treatment of keratinized
Stomatology
11
mucosa, chronic periodontitis and
edentulism, and for gingiva transplantation.
“Other” indications include giant pigmential
“Wound healing”: epidermolisys bullosa.
nevi, ovarian cysts, esophageal cancer.
“Diabetes”: diabetes mellitus 1 type.
Phases Of Clinical Trial
“Hemostasis”: treatment of haemorrage
during operations, coagulopathies.
Tissue engineering:
Phases of Clinical Trials
“Musculoskeletal disorders”: cuff rotator,
degenerative disk disease, osteonecrosis,
Phase 1
7
non-union of fracture.
Phase 3
2
Phase 4
10
“Cosmetic surgery”: breast reconstruction
Phase 1/2
12
after mastectomy.
Phase 2
21
68
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Platelet-Rich Plasma:
Platelet-Rich
Countries
Plasma Clinical
Australia
1
Bahrain
2
Trials
Canada
3
Finland
1
We tracked trials by the search term
India
2
“platelet rich plasma” registered at the WHO
Iran
13
clinical trials database since 01/01/2013 to
Netherlands
1
31/12/2013. The number of trials tracked is
Qatar
1
38. According to the WHO database, all trials
Spain
2
registered during this period are academic,
UK
2
except one trial, sponsored by Anthrex,
Platelet-Rich Plasma:
USA
6
Inc, although some regenerative medicine
Countries
Japan
4
companies develop technologies of platelet-
rich plasma derivation or products based on it.
The number of countries tracked is 39,
because some trials are multi-centered and
Platelet-Rich Plasma:
involve more than one country.
Databases
Platelet-Rich Plasma:
Australian
ACTRN
2
Indications
Indian
CTRI
1
Iranian
IRCT
12
Musculoskeletal
29
Disorders
International
ISRCTN
2
USA
NCT
14
Dental Surgery
2
Alopecia
4
Dutch
NTR
1
EU
EUCTR
2
Wound Healing
2
Aging
1
Japan
JPRN
4
Platelet-Rich Plasma:
Databases
Platelet-Rich Plasma:
Indications
69
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
blind, prospective, multicenter, controlled trial
Platelet-Rich Plasma:
of 230 patients in the USA demonstrated that
platelet-rich plasma significantly improves
Clinical Trial Phases
clinical outcomes in patients with chronic
tennis elbow compared to the active control
group (URL Ref. 22).
Platelet-Rich Plasma:
Clinical Trial Phases
According to Dori and colleagues (URL Ref. 23),
Phase 1
4
PRP has not been shown to be more effective
Phase 1/2
4
for fracture treatment than enamel matrix
derivative and natural bone mineral.
Phase 2
24
Phase 3
5
These results indicate that platelet-rich plasma
Phase 4
1
is significantly effective compared to placebo,
but its advantages over other medicines are to
be properly investigated.
The most frequent indication for platelet-rich
plasma uses are musculoskeletal disorders,
However, some regenerative medicine
like inflammatory or dystrophic joint and
companies have developed techniques of
muscle lesions.
PRP preparation or medicines based on it and
actively work with them.
Three clinical trials are dedicated to the
treatment of male alopecia.
At the end of 2012, Cytomedix, Inc received
FDA clearance for the use of its Angel
Two clinical trials investigate the use of
Concentrated Platelet-Rich Plasma System
platelet-rich plasma in dental surgery.
for processing a small sample of blood or a
mixture of blood and bone marrow aspirate.
One clinical trial investigates the role of
Another FDA-approved product of this
platelet-rich plasma in skin aging.
company, the AutoloGel™ System, is used
Platelet-rich plasma is used for pain
in clinics for the treatment of chronic, non-
management, improving ligament and muscle
healing wounds.
regeneration, treatment of unhealing wounds,
and ortopaedic injuries. Autologic platelets are
Name of
Product(s)
Indication
Phase
Country
Company
injected in high concentration into an injured
tendon, ligament, or muscle. The platelets
The Arthrex
Trial - Canada
contain growth factors which promote healing.
Anthrex, Inc,
Patellar
ACP® Double
Phase 2
Company -
sponsor of trial
tendinopathy
Syringe System
USA
Some clinical trials investigated this problem
had successfully finished in 2013.
A Phase 1 clinical trial held in Iran investigating
the effect of platelet-rich plasma on pain,
function, and quality of life of patients with
knee osteoarthritis showed that intra-articular
knee injection of platelet-rich plasma can
decrease joint pain and stiffness, and improve
patients’ quality of life (URL Ref. 21). A double-
70
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Demographics
Gene Therapy
Australia
1
Clinical Trials
GeneTherapy : Demography
Canada
1
China
5
We tracked Gene Therapy trials by following
France
4
the search terms “gene therapy, genetic
Germany
1
therapy, lentivirus, lentiviral, retrovirus,
Italy
3
retroviral, adenovirus, adenoviral, adeno-
Japan
6
associated, vaccinia, antisense, miRNA, siRNA,
Netherlands
4
shRNA, cDNA, electroporation, lypofection, and
South Africa
1
herpes simplex virus” and manually excluded
Spain
3
trials not related to gene therapy .
Sweden
3
We have excluded trials related to use of
UK
6
viral vaccines for homologous use, like
USA
23
treatment of adenovirus respiratory infections
with adenoviral vaccine, and also to peptide
Number of countries mentioned is 61, because
vaccines. We have excluded research related
some trials are multi-centered.
to use of nucleic acids for diagnostic purposes
like tumor phenotyping in cancer.
Sponsorship
We took data about trial ID, country, phase,
indication, vector, donor type, material
All trials were divided into 2 categories -
delivered into macroorganism, type of
“Academic” or “Commercial.” “Academic” trials
sponsorship, name of company-sponsor, and
are supported by non-profit organizations, and
product from each trial’s description. The
“Commercial” trials are sponsored by profit-
number of trials tracked is 50.
seeking agencies.
Database
GeneTherapy:
Type of
Representation
Sponsorship
Gene Therapy: Databases
Academic
39
Commercial
11
Dutch
NTR
1
Australian
ACNTRN
1
Chinese
ChiCTR
1
Genetic Vector’s Type
International
ISRCTN
2
Japanese
JPRN
6
US
NCT
38
GeneTherapy : Type of vector
African
PACTR
1
Adeno-Associated Virus
4
Adenovirus
14
DNA
1
Herpes Simplex Virus Type 1
2
Lentivirus
12
RNA
6
Retrovirus
5
Vaccinia Virus
6
71
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
“Vector” is a vehicle used to deliver artificial
of cancer, HIV/AIDS, and X-linked Chronic
nucleic acid into a recipient cell. We were
Granulomatous Disease.
able to identify several vector types applied
6 trials used Vaccinia Virusesor Modified
for genetic material delivery in clinical trials
Vaccinia Ankara Virus viruses for safe delivery
registered in the WHO database.
of genetic material for in vivo treatment of HIV/
“Adenovirus” refers to adenoviral vectors.
AIDS. One trial was dedicated to application
Adenoviral vectors are double-strand DNA-
of Modified Vaccinia Ankara virus for oncolytic
based vectors which are used for genetic
purposes.
delivery into epithelial cells. Genetic material
is transcribed together with a host genome,
Approach To
but not incorporated into it. According to WHO
database data, these vectors are used for
Modification
cancer treatment as oncolytic adenoviruses,
the means for immune cell modification.
GeneTherapy : Approach to modification
“Adeno-Associated Virus” is a type of viral
vector that has some typical features. These
double-strand DNA-based vectors cause
very mild immune response. Some of them
In Vivo
30
integrate into a known locus of a genome, and
In Vitro
20
the modified AAV lost the ability to integrate
into a host’s genome at all. Tracked trials
referred to AAV coding antibodies at HIV/AIDS,
ARSA gene for metachromatic leucodystrophy,
genetic modifications of immune cells, and
“In vivo” use of a genetic vector means it is
DNA coding small hairpin RNA for Hepatitis C
delivered into the bloodstream, into solid
treatment.
tumor mass, or into eye tissues.
One trial assessed use of direct DNA delivery
“In vitro” use of genetic vectors refers to
into host cells in vivo by electroporation.
genetic modifications of cells in vitro conditions
with subsequent transfer of these cells into a
Two trials used herpes simplex virus type 1
host organism.
vectors with oncolytic activity.
Twelve clinical trials were based on lentiviral
Gene Therapy: Type
vectors. These integrating RNA-vectors can
affect both dividing and non-dividing cells.
Of Material Delivered
Usually, such integrating vectors are used
for in vitro modification of immune cells, but
Into Cells
one trial investigated in vivo gene delivery in
treatment of retinitis pigmentosa.
GeneTherapy :
Material Delivered
Direct delivery of microRNA, small interfering
Gene
17
RNA, or antisense RNA for inducing RNA-
Genetically Modified
20
interference-mediated destruction of
Cells
pathological RNA was used in 6 trials.
Oncolytic Virus
7
siRNA / miRNA /
6
5 trials referred to use of retroviral vectors.
shRNA / antisense RNA
Application of these integrating and replicating
RNA vectors is limited because of possible
By “genes” here, we tracked trials assessing
insertional mutagenesis. However, we tracked
in vivo delivery of genetic material into a host
trials assessing use of these vectors for in
organism.
vitro modification of host cells for treatment
72
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
We mark out “genetically modified cells”
because delivery of necessary genes in vitro
“Immune Disorders” includes HIV/AIDS,
into immune or cancer cells is a frequent
ADA immunodeficiency, and X-linked
approach in gene therapy.
chronic granulomatous disease.
Seven trials used vectors for oncolytic
“Neurological Disorders” includes
purposes.
metachromatic leukodystrophy and
Six trials were based on direct or indirect
cerebral adrenoleucodystrophy.
delivery of RNAs acting on RNA interference
“Hepatic Disorders” refers to liver fibrosis
process in vivo conditions.
and hepatitis C treatment.
“Cardiovascular Disorders” assesses use of
Source Of Donorship
genetic vectors for ischemic heart disease
treatment.
“Ophtalmological Disorders” includes one
trial dedicated to retinitis pigmentosa
GeneTherapy : Source of
Donorship
treatment.
Autologous
20
“Diabetes” refers to one trial related to
Allogeneic
2
diabetes mellitus type 2 treatment.
Non-Cellular
30
Phases Of Clinical
Trials
The number of mentioned approaches is
52, because two trials assessed use of both
Gene Therapy: Phases
allogeneic and autologous cells.
of Clinical Trials
Phase 1
32
“Non-cellular” refers to direct use in vivo of
Phase 1/2
9
viral vectors.
Phase 2
8
“Autologous” means use of autologous cells
Phase
1
2/3
for genetic modifications in vitro conditions.
“Allogeneic” is related to two trials comparing
use of autologous and allogeneic cells for
Only one trial registered during 2013 and
genetic modification.
several clinical trials are currently at phase 2/3.
We searched for all available results of
Indications
clinical trials finished or published in 2013 and
related to stem cell therapy, gene therapy,
Gene Therapy: Indications
and tissue engineering in terms of the ARMIF
model. We subdivided all these results into
Immune Disorders
12
groups according to phase of clinical trial and
Cancer
31
mentioned them in chronological order.
Neurological Disorders
2
Hapatic Disorders
2
Cardiovascular
1
Opthamological
1
Diabetes
1
73
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Companies And Products Acting In
Gene Therapy
Phase
Name of company
Product(s)
Indication
Country
Lenti-D product candidate, based
on lentiviral vector, involves the ex
Bluebird bio
vivo insertion of a functional copy
Cerebral adrenoleucodystrophy
Phase 2/3
USA
of the ABCD1 gene into a patient's
own hematopoietic stem cells.
An EnGeneIC Delivery Vehicle
(EDV) is an anucleate bacterially
derived minicell. EDVs can be
loaded with chemotherapy, in this
EnGeneIC Ltd
Advanced Solid Tumors
Phase 1
Australia
case either cytotoxic drug or siRNA
or miRNA. The EDV is coated with
EGFR antibodies to enable it to
attach to cancer cells.
GL-ONC1 is a genetically stable
Cancer, malignant tumor
Genelux corporation
oncolytic virus based on modified
Phase 1
USA
effusion
vaccinia virus (Lister strain).
Lentiviral vector containing XCGD
X-linked chronic granulomatous
France
Genethon
gene (restores NADPH oxidase
Phase 1/2
disease
function)
Ichor Medical Systems,
TriGrid™ Delivery System for DNA
HIV/AIDS
Phase 1
USA
Inc
drugs
ISIS-GCCRRx, an RNA antisense
Isis Pharmaceuticals
glucocorticoid receptor antagonist
Diabetes mellitus, type 2
Phase 2
Canada
MRX34, MicroRNA miR-RX34
Primary liver cancer, liver
Mirna Therapeutics, Inc
Liposome Injectable Suspension
Phase 1
USA
metastases.
Ad5-SGE-REIC/Dkk3, adenovirus
vector that is a transport
mechanism to infuse the REIC
Motomaro-gene, Inc
protein into the cell providing a
Prostate cancer
Phase 1/2
USA
temporary transfusion of protein
that induces apoptosis in target
cancer cells.
ND-L02-s020, a Vitamin A-Coupled
Nitto Denco Corporation
Lipid Nanoparticle Containing
Liver fibrosis
Phase 1
USA
siRNA Against HSP47
Profectus Biosciences,
GeneVax® DNA vaccines
HIV/AIDS
Phase 1
USA
Inc
TT-034 is a DNA construct that
codes shRNA which which targets
three highly-conserved regions
Tacere Therapeutics, Inc
Hepatitis C
Phase 1/2
USA
of the Hepatitis C Virus (HCV). It is
introduced in living cells via AAV
vector.
AD-RTS-IL12, adenovirus Vector
Ziopharm
Engineered to Express hIL-12
Glioblastoma
Phase 1
USA
(INXN-2001)
74
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
drug that is designed to inhibit the production
of C-reactive protein.
Results of
(URL Ref. 26)
Clinical Trials
On March 21, 2013, BrainStorm Cell
Therapeutics, a developer of adult stem
Results of Phase I/IIa trials
cell technologies for neurodegenerative
diseases reported some of the final results
On January 16, 2013 - Stratatech Corp.
from a clinical study evaluating the company’s
announced results from its proof-of-concept
NurOwn™ technology in 12 ALS patients. All
clinical trial of StrataGraft®, a universal
patients demonstrated significantly slower
human skin substitute based on the NIKS®
decline in respiratory function and clinical
human keratinocyte progenitor cell line and
condition. The trial proved the safety of
being developed for the treatment of severe
cell therapy, and the company is currently
burns. 19 of 20 patients avoided the need
conducting a Phase IIa dose-escalating trial.
for autograft surgery and regrafting at their
NurOwn™ technology is treatment based on
StrataGraft-treated sites because of complete
autologous bone marrow-derived stem cells
wound closure within 3 months. In addition, no
differentiated into neuron-supporting cells.
StrataGraft tissue residual DNA was observed
after 3 months.
(URL Ref. 27)
(URL Ref. 24)
In May 2013, ReNeuron published interim
results from the first nine patients treated
On February 14, 2013, Gamida Cell reported
in the Phase I PISCES study. The results
the successful results of the Phase I/II study
were presented by the clinical team from
of its product NiCord, umbilical cord-derived
Glasgow’s Southern General Hospital at the
stem cells expanded using the company’s
22nd European Stroke Conference in London,
proprietary NAM technology. Eleven patients,
proving the safety of ReNeuron’s ReN001 stem
ages 21-61, with high-risk hematological
cell therapy in treatment of ischaemic stroke.
malignancies received NiCord and an un-
manipulated graft of umbilical cord blood.
(URL Ref. 28)
Eight patients engrafted with NiCord. The
median time to neutrophil engraftment was
Cancer vaccine company DCPrime on May 28,
10.5 (7-18) days for those engrafting with
2013 announced the successful completion of
NiCord. Two patients engrafted with the un-
its Phase I/IIa study in acute myeloid leukemia
manipulated UCB and one patient experienced
(AML). The study establishes the safety and
primary graft failure. There were no cases of
feasibility of vaccination with DCPrime’s lead
Grade III/IV acute GvHD. No safety concerns
product DCP-001, and shows clear evidence
surrounding the use of NiCord were raised.
of a positive vaccination-induced immune
With a median follow-up of 8 months, the
response. Several patients from 12 studies
progression-free and overall survival are both
demonstrated prolonged survival compared to
90%.
historic expectations.
(URL Ref. 25)
(URL Ref. 29)
On March 13, 2013, Isis Pharmaceuticals,
In June 2013, the Journal of Translational
Inc. announced results of Phase 1 trial of
Medicine published an article demonstrating
ISIS-CRPRx that selectively reduced severe
results of Stempeutics Research Company’s
elevations in C-reactive protein (CRP) in healthy
clinical trial. A double blind. randomized
humans without changes in other immune
placebo-controlled phase I/II study indicated
modulators. ISIS-CRPRx is currently being
the safety and efficacy of allogeneic bone
evaluated in a Phase 2 study in patients with
marrow-derived mesenchymal stem cells in
rheumatoid arthritis. ISIS-CRPRx is an antisense
critical limb ischemia.
75
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
(URL Ref. 30)
without causing acute GvHD.
In June 2013, the journal Transplantation
(URL Ref. 34)
published an article dedicated to a pilot
On September 19, 2013, Isis Pharmaceuticals,
study by Citospin. The pilot trial was aimed
Inc. reported follow-up preliminary data from
at evaluating the feasibility and safety of
a single-dose, open-label Phase 1 study of
osteoarthritis treatment with mesenchymal
ISIS-SMNRx in children with spinal muscular
stromal cells in 12 patients. The trial confirmed
atrophy (SMA). Results showed that most SMA
the safety of intervention and demonstrated
children receiving the two highest doses of
significant improvement in patients’ condition,
the drug (6 mg and 9 mg) continued to show
examination, and testing results.
improvements in muscle function tests up to 14
(URL Ref. 31)
months after a single injection. Positive results
on Phase 1 trial were published in March of
On July 9, 2013, an article reporting the results
2013. ISIS-SMNRx is an antisense drug designed
of a Phase I/II clinical trial, organized by Tianhe
to alter the splicing of the SMN2 gene and to
Stem Cell Biotechnologies, was published
increase production of fully functional SMN
in the journal BMC Medicine. Clinical findings
protein. SMN2 is a gene closely related to
indicate that type 2 diabetes patients achieved
SMN1, in which a defect leads to a decrease
improved metabolic control and reduced
in the survival motor neuron (SMN) protein and
inflammation markers after receiving Stem
death of spinal motoneurons.
Cell Educator therapy. Stem Cell Educator
therapy supposes circulation of patients’
(URL Ref. 35)
blood in a closed-loop system that separates
(URL Ref. 36)
mononuclear cells and promotes their contact
with adherent allogeneic cord blood cells.
On September 20, 2013, Cytori Therapeutics
The study also demonstrated improvement of
announced positive early data of a safety
insulin resistance and beta-cell function after
classification from a study evaluating Cytori’s
Stem Cell Educator therapy.
cell therapy as a potential treatment for
scleroderma. 12 patients received Cytori’s cell
(URL Ref. 32)
therapy (autologous adipose-derived stem
Stemedica Cell Technologies, Inc. announced
cells) in the form of finger injections. The trial
on July 10, 2013 the completion of enrollment
has safety approval for manipulation and has
and treatment of patients suffering from
demonstrated significant improvement in hand
ischemic stroke in a Phase I study with
function.
Stemedica’s lead product Stemedyne-
(URL Ref. 37)
MSC. The trial involved 15 patients and
demonstrated the safety of the company’s
On September 26, 2013, Bioheart, Inc.,
product, allowing trial to proceed to approval
a biotechnology company, announced
for Phase II.
preliminary results of a Phase I trial
investigating the safety and efficacy of
(URL Ref. 33)
AdipoCell™, adipose-derived stem cells, in
On September 11, 2013, Kiadis Pharma
patients with congestive heart failure. The trial
published positive results of a completed five-
evaluated safety and functional cardiovascular
year follow-up of its Phase I/II Clinical Study
system tests at time points of 0, 3, 6, and 12
with Blood Cancer Product ATIR™ that proved
months post-stem-cell injection. Significant
the safety, effectiveness, and high 5-years
functional improvement of cardiovascular
survival rate of graft recipients. ATIR™ is a cell-
system was observed in patients at 3 months
based medicinal product enabling stem cell
after injection.
transplantations using partially mismatched
(URL Ref. 38)
(haploidentical) family members as donors for
patients suffering from blood malignancies
76
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
On September 26, 2013, Celladon Corporation
(URL Ref. 42)
announced the full, three-year long-term
On November 1, 2013, Cellular Biomedicine
follow-up results from Phase 2a of the CUPID
Group announced completion of patient
1 trial. Patients treated with the company’s
treatment for a Phase I/IIa clinical trial for
product, MYDICAR (adenoassociated viral
treatment of knee osteoarthritis with ReJoinTM,
vector coding endoplasmatic reticulum
a human adipose-derived mesenchymal
enzyme SERCA1), demonstrated stable
precursor cell. Patients had a clinically
lower levels of cardiovascular and terminal
meaningful reduction in pain and an increase
complications of advanced heart failure. Now,
in mobility, with a significant improvement
the company moves forward to Phase 2b trial.
(P<0.05) from the baseline in some clinical
Results are anticipated in the first half of 2015.
scores, and no serious adverse events were
(URL Ref. 39)
reported for the duration of the trial.
On October 21, 2013, StemCells, Inc.
(URL Ref. 43)
announced results of a long-term follow-
On December 2, 2013, Biom’Up, a
up study in Batten Disease (neuronal ceroid
manufacturer of absorbable medical implants,
lipofuscinosis). Results of the four-year
announced the results of a clinical study in
observation of NCL patients had been involved
pediatric cardiac surgery. The Phase I study
in a Phase I study. The data provides long-
in 36 patients aimed to evaluate the use of
term evidence of safety, up to five years post
COVATM+, a collagen membrane preventing
transplantation, for the surgical transplantation
the formation of postoperative adherences.
of the HuCNS-SC cells into multiple sites in the
The trial proved the safety of the company’s
brain, and at doses of up to one billion cells.
product and simplified surgical interventions.
(URL Ref. 40)
(URL Ref. 44)
On October 21, 2013, Tissue Regenix Group
On December 7, 2013, ZIOPHARM Oncology,
plc announced full trial results into the
Inc. announced positive interim results from
effectiveness of DermaPure™ in healing
its ongoing Phase 1/2 study of Ad-RTS-IL-12,
treatment-resistant chronic wounds. The
a novel DNA-based therapeutic candidate
results show that patients who had chronic
that is being evaluated with the oral activator,
wounds for an average of 4½ years and who
Veledimex, in patients with advanced
were treated with a single application of Tissue
melanoma. In this study, 21 patients with
Regenix’s dCELL® Dermis, saw an average
unresectable, recurrent stage III/IV melanoma
87% reduction in the size of all wounds, while
have been treated with intratumoral injections
60% of patients were completely healed, with
of Ad-RTS-IL-12 and the oral activator
virtually no recurrences. DermaPure is an
Veledimex. The oral activator controls IL-12
acellular dermis matrix.
mRNA with an on-off mechanism, supposing
(URL Ref. 41)
return of IL-12 mRNA expression to baseline
after stopping of Veledimex administration.
Living Cell Technologies Limited on
Observable adverse effects were pyrexia,
November 1, 2013 announced the findings
hypotension, mental status changes, and
of DIA-09-a Phase I/IIa clinical trial of
cytokine release syndrome. In June of 2013, the
DIABECELL®, therapeutic porcine cell
company published positive results of a phase
implants in patients with type 1 diabetes.
1 trial that accessed use of Ad-RTS-IL-12 trial in
The non-randomised, open label study was
7 patients with grade III/IV melanoma.
conducted at the Hospital Eva Perón, Buenos
Aires, Argentina. Significant positive clinical
(URL Ref. 45)
and laboratory test results demonstrated the
(URL Ref. 46)
effectiveness and safety of the company’s
product.
On December 9, 2013, biotechnology company
77
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
MOLOGEN AG finished the treatment phase
and efficacy data from two Phase 2 studies
of the clinical trial phase I for MGN1703. In
performed in patients undergoing hernia repair
terms of safety and tolerability, no significant
by open laparotomy, another study in patients
clinical events were observed to date.
undergoing open gynecological surgery,
MOLOGEN expects that first results will
and a feasibility study in patients undergoing
become available in early 2014. MGN1703
laparoscopic hernia repair.
is based on dSLIM® (“double Stem Loop
On April 22, 2013, Mesoblast Limited reported
Immunomodulator”), a DNA-based TLR9
positive interim results in a phase 2 trial of
agonist developed by MOLOGEN.
allogeneic Mesenchymal Precursor Cells (MPC,)
(URL Ref. 47)
adult stem cells for intervertebral disc repair. A
single low-dose injection of MPCs resulted in
On December 18, 2013, Targazyme, Inc.,
significantly greater reduction in low back pain,
previously named America Stem Cell, Inc.,
significantly greater improvement in function,
published results of Phase I/IIa trial of
and significantly greater treatment success
Targazyme’s lead product, TZ101, an enzyme-
compared with controls. The complete results
based treatment for use in cell transplants.
of phase 2 trial covering 100 patients were
It is comprised of a recombinant enzyme,
expected to be published in late 2013.
-1,3 fucosyltransferase VI (FTVI), and its
substrate, GDP-fucose. TZ101 is designed to
(URL Ref. 50)
add a sugar (fucose) to the surface of stem
(URL Ref. 51)
cells thus improving homing to bone marrow
in patients receiving hematopoietic stem cell
On April 22, 2013, Transgene SA published
transplantation. The study evaluated the safety
information about final data of the Phase 2
and efficacy of TZ101 together with cord blood
HCVac trial of TG4040 for the treatment of
transplantation in patients with hematologic
genotype 1 chronic hepatitis C (CHC). The
malignancies and myelodysplastic syndrome.
control arm was treated with a combination
TZ101 significantly improved engraftment of
of ribavirin(R) and PegIFN2a(P), while arm B
neutrophils and platelets in bone marrow.
patients got injections of TG4040 after R+P
therapy and arm C patients were pre-treated
(URL Ref. 48)
with TG4040. The positive effect of TG4040
On December 18, 2013, California Stem Cell,
was seen with pre-treatment of TG4040 with a
Inc. announced the successful completion of a
complete early viral response (cEVR) of 64% as
Phase I clinical trial investigating the safety of
compared to 30% in the control arm. TG4040
a cancer stem cell-based therapy in patients
immunotherapeutic product is a recombinant
with Stage IV hepatocellular carcinoma. DC-
vector based on the modified vaccinia virus
TC treatment is based on directing dendrytic
carrying and expressing three of the major non-
cells to recognize cancer stem cells of a
structural proteins (NS3, NS4 and NS5B) of the
patient in vitro conditions with subsequent
hepatitis C virus.
transplantation of cells into a patient organism.
(URL Ref. 52)
(URL Ref. 49)
On July 22, 2013, Oxford BioMedica, a gene-
Results of Phase II and IIb trials
based biopharmaceutical company, announces
® plus chemotherapy
that analyses of a TroVax
On February 2, 2013, Innocoll, Inc. announced
drug Docetaxel (Taxotere®) versus Docetaxel
that the following series of three articles
alone Phase II study in patients with castration-
presenting Phase 2 clinical data for its
resistant prostate cancer (CRPC) have been
bupivacaine-collagen implant, XaraColl®, have
accepted for publication in the peer-reviewed
recently been published in the Journal of Pain
medical journal Cancer Immunology and
Research (JPR). XaraColl is currently in Phase
Immunotherapy, the official journal of the
3 development for postoperative analgesia,
Association for Cancer Immunotherapy. The
and the three articles present the safety
78
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
study enrolled 25 patients with CRPC. TroVax®
reduction in triglyceride and ApoC-III levels.
was well-tolerated in all the patients, while
In September 2013, the company announced
patients treated with TroVax plus Docetaxel
data from a Phase 2 study of ISIS-APOCIIIRx
showed a greater median-progression free
used as a monotherapy in patients with familial
surval of 9.67 months compared to 5.10
chylomicronemia syndrome. Results showed
months for patients treated with Docetaxel
substantial reductions of triglycerides and
only. TroVax® (MVA-5T4) is a therapeutic
Apoc-III levels. In July 2013, the company
cancer vaccine containing modified vaccinia
published results of a Phase 2 trial on ISIS-
virus Ankara (MVA) vector, encoding the 5T4
APOCIIIRx that demonstrated significant
antigen.
reductions of ApoC-III and triglycerides in
patients with high triglycerides taking fibrates.
(URL Ref. 53)
In June 2013, the company announced Phase
2 Data on ISIS-APOCIIIRx in patients with high
(URL Ref. 54)
triglycerides and Type 2 Diabetes. Results
On September 3, 2013, Transgene SA
showed significant reductions in triglycerides
announced that TRAVERSE, a randomized
and APOC-III and improvements in glucose
Phase 2b study of Pexa-Vec in second-line,
control and insulin sensitivity. ISIS-APOCIIIRx
advanced liver cancer patients. failed to meet
is an antisense drug that inhibits APOC-III, a
its primary endpoint of overall survival for
protein that regulates triglyceride metabolism
Pexa-Vec plus best supportive care (BSC)
in blood.
compared to BSC. The company is waiting for
(URL Ref. 57)
results of ongoing clinical trials of Pexa-Vec for
kidney, colorectal, and ovarian cancer. Pexa-
(URL Ref. 58)
Vec is a modified vaccinia virus modified with
GM-CSF, which promotes immune response.
(URL Ref. 59)
(URL Ref. 55)
(URL Ref. 60)
On November 18, 2013, Biocardia, Inc.
On December 4, 2013, regenerative medicine
published positive 12-month results for the
company Mesoblast Limited announced
randomized Transendocardial Autologous
top-line results from the Phase 2 trial of its
Cells (MSC or BMC) in an Ischemic Heart
proprietary Mesenchymal Precursor Cells
Failure Trial (TAC-HFT). The phase II trial
(MPCs) in subjects with type 2 diabetes. The
demonstrated the safety of trans-endocardial,
results of the trial support the safety and
autologous, culture-expanded mesenchymal
tolerability of a single intravenous infusion of
cells (MSCs) and autologous bone marrow
MPCs in type 2 diabetes.
mononuclear cells (BMCs) delivered by
(URL Ref. 61)
the company’s Helical Infusion Catheter
System™ in the treatment of chronic ischemic
On December 12, 2013, Integra LifeSciences
cardiomyopathy (ICM). Significant quality of life
announces the NeuraGen® Clinical Study
improvement was observed in patients treated
published in the Journal of Hand Surgery.
with this procedure. Statistical difference
A two-year follow-up of a controlled,
between therapy and placebo was observed
randomized, blind multi-center study of
in part of the functional tests and ultrasound
peripheral nerve repair, comparing NeuraGen®
measurements.
Nerve Guide to the conventional method
of direct suture repair in patients who had
(URL Ref. 56)
complete traumatic nerve injuries to the
On November 18, 2013, Isis Pharmaceuticals,
median and/or ulnar nerves. Results from
Inc reported a fifth positive Phase 2 data set
32 patients completed within a two-year
for use of ISIS-APOCIIIRx as a monotherapy
postoperative period demonstrated equivalent
in patients with very high to severely high
effectiveness of the company’s product in
triglycerides that demonstrated significant
the repair of major mixed motor and sensory
79
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
nerves comparing to the “gold standards” of
is being developed by Merck under a license
surgical repair.
agreement with Oncothyreon. Overall,
a survival rate of 30,8 (after Tecemotide
(URL Ref. 62)
treatment) months comparing with 20,6
months (placebo) was observed, although a
On December 18, 2013, Osiris Therapeutics,
primal endpoint of survival extension was not
Inc. announced data published in the
met.
December issue of Ostomy Wound
Management. Results show that the use
(URL Ref. 66)
of Grafix® on a variety of chronic wounds
resulted in an overall closure rate of 76% by 12
(URL Ref. 67)
weeks, including 68% of Venous Leg Ulcers
GlaxoSmithKline (GSK) and Prosensa on
(VLUs) and 85% of Diabetic Foot Ulcers (DFUs)
September 20, 2013 announced that GSK’s
treated. Grafix is a human cellular matrix
Phase III clinical study of Drisapersen, an
containing living stem cells for acute and
antisense oligonucleotide, for the treatment
chronic wounds.
of Duchenne Muscular Dystrophy patients
(URL Ref. 63)
with an amenable mutation, did not meet the
primary endpoint of a statistically significant
Results of Phase II/III and III trials
improvement in tests compared to placebo.
On February 4, 2013, Gamida Cell’s StemEx®
(URL Ref. 68)
announced achievement of a primary endpoint
in a Phase II/III clinical study which compared
the use of StemEx as part of a transplantation
regimen to historical controls in the treatment
of patients with hematological malignancies
such as leukemia and lymphoma. The primary
endpoint is defined as the rate of mortality
(%) within 100 days after transplantation. The
analysis shows 15.8% mortality in the StemEx
group and 24.5% in the control group
(p=0.034). The study also demonstrated
increased number of patients with early
hematopoietic recovery and shortened time
of neutrophil and platelet engraftment. But
the survival advantage was not statistically
significant by day 180, with mortality of 32.7%
in the StemEx® group and 34.7% in the control
group (p=0.39) and the same frequency of
severe acute graft versus host disease was
observed in both groups.
(URL Ref. 64)
(URL Ref. 65)
Merck Serono, a division of Merck, Darmstadt,
Germany, on May 16, 2013 announced detailed
results from the randomized Phase III START
trial of its investigational MUC1 antigen-specific
cancer vaccine L-BLP25 in patients with
unresectable, locally-advanced Stage III non-
small cell lung cancer (NSCLC). Tecemotide
80
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
company must demonstrate that its devices
provide a reasonable assurance of safety
Market
and effectiveness. Special agencies are
responsible for regulation and supervision
Approvals
of these processes. We analyzed information
related to stem cell, gene therapies, and
Market approval allows high-risk medicine or
tissue engineering approval by the following
intervention to be involved in marketing. To
organizations:
receive such an approval, the manufacturing
Food And Drug Administration (USA)
International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH)
National Health Surveillance Agency (Brazil)
Marketed Health Products Directorate (Canada)
European Medicines Agency (EU)
Pharmaceuticals and Medical Devices Agency (Japan)
Federal Commission for the Protection Against Sanitary Risk (Mexico)
Medicines and Healthcare Products Regulatory Agency (UK)
Australian Therapeutic Drug Administration (Australia) ANZTPA
Drug Controller General of India
In 2013, the FDA approved two biological
FDA
interventions and one tissue-engineered
implant:
Approvals
HPC, Cord Blood;
FDA regulates market approval of new drugs
Allocord;
in the USA. Cell, gene therapy, and tissue
engineering are classified as “biologics” by the
Juvéderm Voluma XC - P11003
FDA.
81
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Name
Description
Indication
Manufacturer
Country
hematopoietic
Cord blood, allogeneic cord blood
LifeSouth Community Blood Centers,
HPC, Cord Blood
and immunologic
USA
hematopoietic progenitor cell therapy
Inc.
reconstitution
hematopoietic
Cord blood, allogeneic cord blood
SSM Cardinal Glennon Children’s
Allocord
and immunologic
USA
hematopoietic progenitor cell therapy
Medical Center
reconstitution
Sterile, biodegradable, viscoelastic
Juvéderm Voluma XC -
gel implant. It consists of crosslinked
Cosmetic surgery, age-
Juvéderm Voluma
Allergan
P110033
hyaluronic acid produced by
related skin changes
XC
Streptococcus equi bacteria
(URL Ref. 69)
(URL Ref. 70)
European Medicines Agency Approvals
The European Medicines Agency evaluates new drugs for market approval in the European Union.
Gene-therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and
combined advanced-therapy medicines are classified as “advanced therapies” by this agency.
Name
Description
Indication
Manufacturer
Country
PROVENGE® (SIPULEUCEL-T) cellular immunotherapy
Asymptomatic or minimally
made by autologous immune cells with a recombinant
symptomatic
Provenge
Dendrion
USA
prostate-specific antigen PAP-GM-CSF. It activates T
metastatic castrate-resistant
cells to target and attack prostate cancer cells.
prostate cancer in male adults
MACI (“Matrix-induced
Tissue-engineered product made of matrix-induced
Sanofi Biosurgery,
autologous chondrocyte
autologous chondrocytes. Matrix is formed of porcine
Repair of damaged cartilage
USA
Genzyme
implantation)
collagen.
(URL Ref. 71)
(URL Ref. 72)
82
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Notable
Public Companies
8
BioTime, Inc.
Ticker symbol: BTX
Year of foundation: 1990
Address: 1301 Harbor Bay Parkway, Suite 100, Alameda, CA 94502, United States
Phone number: +1-510-521-3390
Fax number: +1-510-521-3389
Web-site: http://www.biotimeinc.com/
Profile: BioTime is an internationally operating biotechnology company focused on the emerging
field of regenerative medicine. Leading products of BioTime include blood plasma volume
expander Hextend, PureStem™ cell lines, HyStem® hydrogels, culture media, and differentiation
kits.
Through its specialized subsidiaries, the company develops and markets products based on
human embryonic stem cell and induced pluripotent stem cell technology. BioTime’s subsidiary
Cell Cure Neurosciences Ltd. is involved with the development of products derived from stem
cells for the treatment of retinal and neural degenerative diseases. OrthoCyte Corporation is a
BioTime subsidiary, developing stem cell based therapeutic solutions to treat orthopedic diseases
and injuries. Another subsidiary, OncoCyte Corporation, focuses on the diagnostic and therapeutic
applications of stem cell technology in cancer and includes the diagnostic product PanC-Dx™,
currently being developed for the detection of cancer in blood samples.
One of the major BioTime subsidiaries, ReCyte Therapeutics, Inc., is developing products based
on induced pluripotent stem cell technology to reverse the developmental aging of human cells
and to treat cardiovascular and blood cell diseases. ReCyte Therapeutics owns the license to use
ACTCellerate technology, developed by Advanced Cell Technology, Inc. (ACT,) to produce and
market its human embryonic progenitor cells (hEPCs), called PureStem cell lines. Commercial
distribution of PureStem hEPCs is realized through LifeMap Sciences, Inc. (LifeMap Sciences).
LifeMap Sciences, Inc. also markets GeneCards, the leading human gene database and
MalaCards, the human disease database.
Another subsidiary, ES Cell International
Pte. Ltd (ESI), has developed and markets
hES cell lines. ESI has agreements with
the California Institute of Regenerative
Medicine (CIRM) and the University of
California to distribute its hES cell lines to
research institutes in California.
In September 2012, BioTime established
Asterias Biotherapeutics, Inc. (formerly
known as BioTime Acquisition Corporation
(“BAC”), a subsidiary created to acquire
Source: Yahoo Finance
the stem cell assets of Geron Corporation
(NASDAQ: GERN). In October and
November 2012, Asterias Biotherapeutics,
84
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Inc. approached Geron with two consecutive proposals, and in July 2013, Asterias Biotherapeutics,
Inc. entered into a definitive Asset Contribution Agreement with Geron to acquire the intellectual
property, including over 400 hES-related patents and patent applications; biological materials
and reagents; lab equipment, and other assets related to Geron’s human embryonic stem
(hES) cell programs, including the Phase I clinical trial of human embryonic stem (hES) cell-
derived oligodendrocytes in patients with acute spinal cord injury, and an autologous cellular
immunotherapy program and the Phase II trial of the therapy in acute myeloid leukemia (as well
as the related INDs for both).
Geron will own 21.4% of Asterias Biotherapeutics, Inc. (BioTime owns the majority, 71.6%, and
a private investor, the rest) will receive a 4% royalty. Separately, BioTime is contributing to
Asterias Biotherapeutics, Inc. $5mm in cash, 8.9mm of its common stock (valued at $30mm),
five-year warrants to buy 8mm shares for $5, rights to use certain clinical-grade hES cell lines,
a nonexclusive global sublicense on stem cell differentiation patents, and minority stakes,
10% and 6%, in two of its subsidiaries, OrthoCyte and Cell Cure Neurosciences, respectively.
Asterias Biotherapeutics, Inc. also received $5mm from the private investor. The company
has a commercial license and option agreement with Wisconsin Alumni Research Foundation
(WARF) to use 140 patents and patent pending technology belonging to WARF, as well as certain
stem cell materials. The company also has a license agreement with Cornell University for
the worldwide development and commercialization of technology developed at Weill Cornell
Medical College for the differentiation of hES cells into vascular endothelial cells.
At the moment, the company owns or licenses more than 400 US patents and US patent
applications. The major customers of BioTime, Inc. are Hospira, Inc.; CJ CheilJedang Corp.; and
Summit Pharmaceuticals International Corporation.
Top management:
Hal Sternberg, PhD, VP, Research
Michael D West, PhD, Pres. & CEO
William. P. Tew, PhD, VP, Bus. Dev. & Chief
Commercial Officer
Robert W Peabody, SVP, COO & CFO
Biotime, Inc. ARMIF
85
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Osiris Therapeutics, Inc.
Ticker symbol: OSIR
Year of foundation: 1990
Address: 7015 Albert Einstein Drive, Columbia, MD 21046-1707, United States
Phone number: +1-510-521-3390
Fax number: +1-510-521-3389
Web-site: http://www.osiris.com/
Profile:
Osiris Therapeutics is a biotechnology company that develops and commercializes products to
treat medical conditions in inflammatory, cardiovascular, orthopedic, and wound healing markets.
Osiris operates in two main segments: therapeutics and biosurgery. The therapeutics segment
offers biologic stem cell drug candidates from bone marrow derived MSCs.
Osiris Therapeutics was the first company to receive marketing clearance for its stem cell drug
Prochymal for the treatment of acute
graft-vs.-host disease (GvHD) in children.
It was the world’s first regulatory approval
of a manufactured stem cell product,
and the first therapy approved for GvHD.
Osiris partnered with the Juvenile Diabetes
Research Foundation (JDRF) for the
development of Prochymal as a treatment
for patients with newly diagnosed type
1 diabetes mellitus. and also joined JCR
Pharmaceutical Corporation to produce
and market Prochymal in Japan. Another
product in the therapeutic segment is called
Source: Yahoo Finance
Chondrogen and is aimed at osteoarthritis
and cartilage protection.
The biosurgery segment develops, manufactures, and markets products for orthopedic, wound
healing, and surgical procedures. The three-dimensional cellular repair matrix Grafix was
developed for the treatment of acute and chronic wounds, including diabetic foot ulcers and
burns. It demonstrated a very high efficacy in the recent multicenter, randomized, controlled
clinical trial comparing the safety and effectiveness of Grafix to the standard of care in patients
with chronic diabetic foot ulcers.
Another product manufactured in this segment, named Ovation, is a cellular repair matrix
designed for bone repair.
In October 2013, Mesoblast LTD acquired Osiris’ culture-expanded mesenchymal stem
cell (ceMSC) business, including Prochymal, in a transaction worth up to $100mm in initial
consideration and milestone payments. Additionally, Osiris will receive royalty payments on sales
of Prochymal and other products utilizing the acquired ceMSC technology.
At the moment, Osiris has an extensive intellectual property portfolio, including 162 foreign
86
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
patents, 45 issued U.S. patents and 13 filed U.S.
patent applications.
Top management.
Lode Debrabandere, PhD, Pres. & CEO
Philip R Jacoby, CFO
Peter Friedli, Chairman of the Board
Michelle LeRoux Williams, PhD, CSO
Stephen W Potter, SVP, Ops. & Corp. Dev
Osiris Therapeutics, Inc. ARMIF
87
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Cytori Therapeutics, Inc.
Ticker symbol: CYTX
Year of foundation: 1996
Address: 3020 Callan Road, San Diego, CA
92121, United States
Phone: +1-858-4580900
Fax: +1-858-4580994
Web-site: http://www.cytori.com/
Profile:
Cytori Therapeutics, Inc. is an internationally
operating biotechnology company
that develops and commercializes cell
therapies based on autologous adipose-
Source: Yahoo Finance
derived stem and regenerative cells to
treat cardiovascular disease and repair soft
tissue injuries.
Cytori has developed the Celution(R) System device technology for processing a mixture of
adult stem cells from adipose tissue. In the U.S., the company focuses on developing therapeutic
applications for the treatment of refractory heart failure and thermal/radiation injuries.
In Japan, Cytori sells its products mainly to researchers at hospitals and medical institutes.
In September 2012, Cytori signed a contract with the Biomedical Advanced Research and
Development Authority (BARDA), a segment of the U.S. Department of Health & Human Services,
to develop cellular therapies for the treatment of thermal and radiation-induced wounds.
The company is currently conducting several clinical trials, including a U.S. safety and feasibility
trial of ATHENA for refractory heart failure treatment and a European trial, ADVANCE, for acute
myocardial infarction.
Cytori has completed enrollment and reported data from two European safety and feasibility
trials, the APOLLO and PRECISE trials, in the areas of acute heart attack and chronic myocardial
ischemia, respectively. The company also has completed the RESTORE 2 trial using autologous
fat grafts enriched with the patient’s own adipose-derived stem and regenerative cells (ADRCs)
in partial mastectomy patients. In February 2013, Cytori received CE Mark approval in Europe for
Intravase, a reagent designed to be used with Cytori’s Celution System for preparing safe and
optimized adipose-derived stem and regenerative cells (ADRCs) for intravascular delivery into the
same patient.
88
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
The company’s intellectual portfolio consists of
over 100 U.S. and internationally issued patents and
patent applications.
Top management:
Christopher J. Calhoun, CEO, Director
Mark E. Saad, CFO
David M. Rickey, Independent Chairman of the Board
Marc H. Hedrick M.D., President, Director
Seijiro N. Shirahama, President , Asia Pacific
Clyde W. Shores, EVP - Marketing & Sales
Cytori Therapeutics, Inc. ARMIF
89
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Mesoblast, Ltd.
Ticker symbol: MBLTY
Year of foundation: 2004
Address: 55 Collins St., Level 39, Melbourne, Victoria 3000, Australia
Phone number: +61-3-9639-6036
Fax number: +61-3-9639-6030
Web-site: http://www.mesoblast.com
Profile:
Mesoblast Ltd. is a biotechnology company
developing stem cell based technologies
for various medical conditions. Mesoblast’s
cell-based core technologies include its
lead Mesenchymal Precursor Cell (MPC)
technology platform, currently used to
develop products derived from bone
marrow and adipose tissue sources, its
Dental Pulp Stem Cells (DPSCs), and
expanded Hematopoietic Stem Cells (HSCs).
Source: Yahoo Finance
The Company’s MPC products are currently
being evaluated in patients with congestive
heart failure, acute myocardial infarction, type 2 diabetes and kidney disease, rheumatoid arthritis,
inflammatory lung diseases, and intervertebral disc disease. In addition, Mesoblast is developing
certain biotherapeutics based on protein factors derived from its proprietary cellular platforms.
The Company operates through its wholly owned subsidiaries Mesoblast, Inc., Mesoblast
International SA, Mesoblast Australia Pty Ltd., and Mesoblast UK Limited. In December 2010,
Mesoblast partnered with Teva Pharmaceutical Industries Ltd. for the development and
commercialization of its Mesenchymal Precursor Cell (MPC) products in a number of fields,
including cardiovascular diseases (in particular, congestive heart failure) and neurologic
conditions.
This strategic partnership provides Mesoblast with a partner who has Phase 3 clinical and
regulatory expertise, proven capability to bring products to market, and global distribution
strength.
In September 2011, Mesoblast and Lonza Group (SWS: LONN), a world leader in biologic
manufacturing, entered into a strategic alliance for clinical and long-term commercial production
of Mesoblast’s off-the-shelf (allogeneic) adult stem cell products. Other commercial benefits
include the ability to reduce cost of goods (COGS) and to provide research support for optimized
second generation products.
This alliance provides Mesoblast with significant commercial advantages, including certainty of
90
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
capacity to meet long-term global supply of its proprietary MPC products, exclusive access to
Lonza’s cell therapy facilities in Singapore, and the potential for a purpose-built manufacturing
facility to be built by Lonza to meet Mesoblast’s long-term commercial objectives. In March
2013, Mesoblast raised $174mm by selling 27mm shares at $A6.30, a 3% discount, to first-time
US inventors and global institutional funds (including M&G Investment Management and Capital
Research) and returning institutional buyers.
The money will be used for a Phase III trial of NeoFuse (consisting of allogeneic mesenchymal
precursor cells (MPCs) in minimally invasive lumbar spinal fusion surgery; Phase II studies of
IV formulations of MPCs for systemic inflammatory indications; optimizing MPC manufacturing
methods and increasing inventory; and for hiring more employees.
In October 2013, Mesoblast LTD acquired Osiris’ culture-expanded mesenchymal stem
cell (ceMSC) business, including Prochymal, in a transaction worth up to $100mm in initial
consideration and milestone payments. Additionally, Osiris will receive royalty payments on sales
of Prochymal and other products utilizing the acquired ceMSC technology.
The company’s intellectual property portfolio comprises around 20 US and international patents
and patent applications.
Top management:
Silviu Itescu, CEO
Jenni Pilcher, CFO
James T Ryaby, PhD, VP, Rsch. & Clinical Affairs
Mesoblast, Ltd. ARMIF
91
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Neostem, Inc.
Ticker symbol: NBS
Year of foundation: 2006
Address: 405 Eagleview Boulevard, Exton, PA 19341, United States
Phone number: +1-212-5844180
Fax number: +1-646-5147787
Web-site: http://www.neostem.com
Profile:
Neostem, Inc. is an internationally operating biopharmaceutical company focused on developing
cell therapy products. The company’s business model includes the development of novel
proprietary cell therapy products, as well as operating a contract development and manufacturing
organization (CDMO) providing services to others in the regenerative medicine industry. Since
2007, NeoStem has been engaged in research and development of new therapies and adult stem
cell technology based on human very small embryonic-like stem cells, or VSELTM Technology,
with the University of Louisville Research Foundation and other academic partners. In October
2011, Neostem acquired Amorcyte, LLC (Amorcyte), a development stage cell therapy company
focusing on novel treatments for cardiovascular disease.
Currently, the company is in a phase 2 of the PreSERVE clinical trial Amorcyte’s proprietary
chemotactic hematopoietic stem cell product AMR-001 is being evaluated for the preservation of
heart function after a severe heart attack.
Neostem’s wholly-owned subsidiary, Progenitor Cell Therapy, LLC (PCT), was acquired in
January 2011 and is a CDMO in the cellular therapy industry with manufacturing, regulatory, and
commercialization expertise for therapeutics
development.
In January 2011, Neostem acquired an
80% ownership of Athelos, a company
developing a T-cell therapeutic with
potential for a range of auto-immune
conditions including graft vs. host disease,
type 1 diabetes, steroid resistant asthma,
lupus, multiple sclerosis, and solid organ
transplant rejection. Neostem’s intellectual
portfolio includes 31 US and internationally
issued patents and 54 pending patent
applications, including composition of
Source: Yahoo Finance
92
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
matter and method claims, and a geographic
breadth of filings.
Top management:
Robin L Smith, MD, Chmn. & CEO
Larry A May, CFO
Martin E Schmieg, VP, Corp. Dev.
Andrew L Pecora, MD, CMO
Neostem, Inc. ARMIF
93
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Advanced Cell Technology, Inc.
Ticker symbol: ACTC
Year of foundation: 1994
Address: 149 Commonwealth Dr., Menlo Park, CA 94025, United States
Phone number: +1-508-756-1212
Fax number: +1-508-229-2333
Web-site: http://www.advancedcell.com
Profile:
Advanced Cell Technology is a
biotechnology company operating in the
United States and internationally. It develops
and commercializes products and services
based on the human embrionic, induced
pluripotent and adult stem technology.
The company focuses on the development
of proprietary methods to generate new cells
to replace malfunctioning or damaged cells.
Being focused on clinical-staged
technologies, the company owns or
Source: Yahoo Finance
licenses more than 200 patents and patent
applications in the field of regenerative
medicine and stem cell therapy. Currently,
the company’s patent portfolio covers broad intellectual property (IP) holdings around its embryo-
safe single-cell blastomere technique and a variety of applications including stem cell-based
methods for production of retinal pigment epithelium (RPE) cells, myoblast stem cells, and
hemangioblasts.
94
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
To fine tune the manufacturing process of human
embryonic stem cell lines using it’s embryo-safe
single-cell blastomere technique, in 2011 ACT
established a partnership with Roslin Cells LTD of
Scotland.
Top management:
Michael T. Heffernan, Chmn.
Edward H. Myles CPA, Interim Pres., CFO, EVP -
Corporate Development
Eddy Anglade M.D., EVP - Clinical Development
Robert P. Lanza M.D., CSO
Advanced Cell Technology, Inc. ARMIF
95
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Organovo, Inc.
Ticker symbol: ONVO
Year of foundation: 2007
Address: 6275 Nancy Ridge Drive, Suite 110, San Diego, CA 92121, United States
Phone number: +1-858-550-9994
Web-site: http://www.organovo.com/
Profile:
Organovo Holdings, Inc. develops and commercializes functional, three-dimensional human
tissues for medical research and therapeutic applications.
The main focus of the company lies on the
development of three-dimensional models
of human tissue for regenerative medicine
solutions (i.e. bio-printed blood vessels
and nerve grafts), drug discovery, and
development.
The company designed the NovoGen MMX
Bioprinter to create 3D tissue constructs
using cellular bio-ink, biocompatible
hydrogel, or a mixture of the two. These
technologies enable the fabrication of
various tissue architectures.
Source: Yahoo Finance
In April 2013, Organovo announced the
production of the first fully cellular 3D bioprinted liver tissue. To manufacture its NovoGen MMX
Bioprinter, Organovo partnered with a third party manufacturer, Invetech Pty., of Melbourne,
Australia.
The company actively collaborates with several major companies and institutes. In 2010,
Organovo Holdings established a collaborative research agreement with Pfizer, Inc. to develop
tissue based drug discovery assays utilizing its NovoGen MMX Bioprinter technology. In 2011, the
company entered into a research agreement with United Therapeutics Corporation to conduct a
research program to discover treatments for pulmonary hypertension. In January 2013, Organovo
and OHSU Knight Cancer Institute established a collaboration for cancer research.
In August 2013, Organovo netted $43.8mm through the public sale of 10.4mm common shares
(including the overallotment) at $4.50. In September 2013, Organovo Holdings, Inc. has entered
into an agreement with The Michael J. Fox Foundation for Parkinson’s Research to develop tissues
for drug discovery. Organovo Holdings, Inc. was founded in 2007 with an IP portfolio obtained
96
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
from the University of Missouri and Clemson
University. To date, Organovo Holdings, Inc. has filed
8 U.S. and foreign patent applications.
Top management:
Keith Murphy, CEO, Chmn., Pres.
Barry D. Michaels, CFO, Corporate Secretary
Sharon Collins Presnell Ph.D., EVP - Research and
Development, Chief Technology Officer
Michael Renard, EVP - Commercial Operations
Eric Michael David Ph.D., Chief Strategy Officer
Richard Heyman Ph.D., Director
Organovo, Inc. ARMIF
97
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
ReNeuron Group also works as a supplier, by
Reneuron Group, Plc.
marketing its proprietary neural stem cell lines
such as ReNcell VM and ReNcell CX.
Ticker symbol: RENE.L
Top management:
Year of foundation: 1997
Address: 10 Nugent Rd, Surrey Research Park,
Bryan Morton, Non-Executive Chmn.
Guildford, Surrey, GU2 7AF, UK
Michael Hunt, CEO
Phone number: +44-0-1483-302560
Fax number: +44-0-1483-534864
John Sinden Ph.D, CSO
Web-site: http://www.reneuron.com
Profile:
ReNeuron Group, Plc. Develops and
commercializes stem cell-based therapies
for a range of neurodegenerative diseases,
Type 1 diabetes, Parkinson’s disease, and
various ocular diseases.
The company’s therapeutic product
pipeline includes ReN001, a pre-clinical
development stage therapy for disabled
stroke patients. The company’s other
therapeutic and non-therapeutic programs
in pre-clinical trials comprise ReN002 for
diabetes, ReN003 for retinal diseases,
ReN004 for Parkinson’s disease, and
Source: Yahoo Finance
ReN005 for Huntington’s disease.
Reneuron Group, Plc. ARMIF
98
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Stem Cells, Inc.
Ticker symbol: STEM
Year of foundation: 1994
Address: 7707 Gateway Blvd., Suite 140 Newark, CA 94560, United States
Phone number: +1-510-456-4000
Fax number: +1-510-456-4001
Web-site: http://www.stemcellsciences.
com
Profile:
StemCells, Inc. is a clinical-stage
biotechnology company focused
on the discovery, development, and
commercialization of cell-based
therapeutics to treat diseases of the central
nervous system and liver. They seek to
Source: Yahoo Finance
address unmet medical needs through the
development of stem cells as therapeutic agents to treat damage or degeneration of major organ
systems. Stem Cells, Inc. product development programs seek to repair or repopulate CNS and
liver tissue that has been damaged or lost as a result of disease or injury.
Stem Cells, Inc. has pioneered the discovery and development of HuCNS-SC® cells, its highly
purified, expandable population of human neural stem cells. Stem Cells has completed a six
patient Phase I clinical trial of its proprietary HuCNS-SC product candidate as a treatment for
neuronal ceroid lipofuscinosis (NCL), a rare and fatal neurodegenerative disease that affects
infants and young children.
Stem Cells has also received approval from the U.S. Food and Drug Administration (FDA) to
initiate a Phase I clinical trial of the HuCNS-SC cells to treat Pelizaeus-Merzbacher Disease (PMD),
also a rare and fatal brain disorder that mainly affects young children. Stem Cells, Inc. owns
or has exclusive rights to approximately 50 issued or allowed U.S. patents and more than 150
granted or allowed non-U.S. patents. Stem Cells Sciences, Plc was acquired by Stem Cells, Inc
in 2009. As a result, StemCells has acquired proprietary cell technologies relating to embryonic
stem cells, induced pluripotent stem (iPS) cells, and tissue-derived (adult) stem cells; expertise
and infrastructure for providing cell-based assays for drug discovery; the SC Proven® media
formulation and reagent business; an intellectual property portfolio with claims relevant to cell
processing, reprogramming, and manipulation, as well as to gene targeting and insertion; and
existing business and license relationships with several major life science companies, such as
Merck and Millipore.
99
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Top management:
John J. Schwartz Ph.D., Indep. Chmn.
Martin M. McGlynn, CEO, Pres., Director
Gregory T. Schiffman, CFO, EVP - Finance
Stewart Craig Ph.D., EVP - Development /
Operations
Ann Tsukamoto Ph.D., EVP - Scientific and
Strategic Alliances
Stem Cells, Inc. ARMIF
100
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
REFERENCES
* Government funding for research projects with certain term mentioned in the abstract or title
according to http://fundingtrends.com/.
American Technion Society (2012, August 14). Engineered pancreatic tissues could lead to
better transplants for diabetics. ScienceDaily. Retrieved November 14, 2013, from http://www.
sciencedaily.com¬ /releases/2012/08/120814110751.htm.
Bao, X., Zhu, X., Liao, B., Benda, C., Zhuang, Q., Pei, D., et al. (2013). MicroRNAs in somatic cell
reprogramming. Curr Opin Cell Biol., 25, 208-14. doi: 10.1016/j.ceb.2012.12.004.
Burnouf, T., Goubran, H.A., Chen, T.M., Ou, K.L., El-Ekiaby, M., Radosevic, M.( 2013) Blood-derived
biomaterials and platelet growth factors in regenerative medicine. Blood Rev., 27, 77-89. doi:
10.1016/j.blre.2013.02.001.
Buzdin AA, Zhavoronkov AA, Korzinkin MB, Venkova LS, Zenin AA, Smirnov PY and Borisov NM,
“Oncofinder, a new method for the analysis of intracellular signaling pathway activation using
transcriptomic data,” Front. Genet. 5:55. doi: 10.3389/fgene.2014.00055
Cai, J., Zhang, Y., Liu, P., Chen, S., Wu, X., Sun, Y., et al. (2013). Generation of tooth-like structures
from integration-free human urine induced pluripotent stem cells. Cell Regeneration, 2:6.
Retrieved from http://www.cellregenerationjournal.com/content/2/1/6/abstract.
Cyranoski, D. (2013). Stem cells cruise to clinic. Japanese study of induced pluripotent stem cells
aims to demonstrate safety in humans. Nature. Retrieved from http://www.nature.com/news/
stem-cells-cruise-to-clinic-1.12511.
Cyranoski, D. (2013). Stem cells reprogrammed using chemicals alone. Patient-specific cells could
be made without genetic manipulation. Nature. Retrieved from http://www.nature.com/news/
stem-cells-reprogrammed-using-chemicals-alone-1.13416
Duffy, M.R., Parker, A.L., Kalkman, E.R., White, K., Kovalskyy, D., Kelly, S.M., Baker, A.H. (2013).
Identification of novel small molecule inhibitors of adenovirus gene transfer using a high
throughput screening approach. J. Control. Release, 170, 132-40. doi: 0.1016/j.jconrel.2013.05.007
Duke, C.M. & Taylor HS. (2013). Stem cells and the reproductive system: Historical perspective and
future directions. Maturitas, 76, 284-9. doi: 10.1016/j.maturitas.2013.08.012.
Falco, M. (2009). FDA approves human embryonic stem cell study. CNN. Retrieved from http://
edition.cnn.com/2009/HEALTH/01/23/stem.cell/
Ginn, S.L., Alexander, I.E., Edelstein, M.L., Abedi, M.R., Wixon, J.(2013). Gene therapy clinical trials
worldwide to 2012 - an update. J Gene Med., 15, 65-77. doi: 10.1002/jgm.2698.
Gupta, R. (2012). Cord blood stem cells: current uses and future challenges. Retrieved from http://
www.eurostemcell.org/factsheet/cord-blood-stem-cells-current-uses-and-future-challenges
Horst, M., Madduri, S., Gobet, R., Sulser, T., Milleret, V., Hall, H., et al. (2013). Engineering functional
bladder tissues. J Tissue Eng Regen Med., 7, 515-22. doi: 10.1002/term.547.
Khamsi, R. (2006). Bio-engineered bladders successful in patients. New Scientist. Retrieved from
http://www.newscientist.com/article/dn8939-bioengineered-bladders-successful-in-patients.
html#.Ulhj43yKCq4.
101
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Lo, K. W., Ashe, K.M., Kan, H. M., Laurencin, C.T. (2012). The role of small molecules in
musculoskeletal regeneration. Regenerative Medicine, 7, 535-549. doi:10.2217/rme.12.33
Maher, B. (2013). Tissue engineering: How to build a heart. With thousands of people in need of
heart transplants, researchers are trying to grow new organs. Nature. Retrieved from http://www.
nature.com/news/tissue-engineering-how-to-build-a-heart-1.13327
Mironov, V., Visconti, R.P., Kasyanov, V., Forgacs, G., Drake, C.J., Markwald, R.R. (2009). Organ
printing: tissue spheroids as building blocks. Biomaterials, 30, 2164-74. doi: 10.1016/j.
biomaterials.2008.12.084.
Perumbeti, A. (2013). Hematopoietic Stem Cell Transplantation. Retrieved from http://emedicine.
medscape.com/article/208954-overview.
Scripps Research Institute (2009, October 19). Major Step In Making Better Stem Cells From
Adult Tissue. ScienceDaily. Retrieved November 14, 2013, from http://www.sciencedaily.com¬ /
releases/2009/10/091018141615.htm
Smith, J.O., Sengers, B.G., Aarvold, A., Tayton, E.R., Dunlop, D.G., Oreffo, R.O. (2012). Tantalum
trabecular metal - addition of human skeletal cells to enhance bone implant interface strength
and clinical application. J Tissue Eng Regen Med. doi: 10.1002/term.1525.
Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., et al. (2013). Vascularized
and functional human liver from an iPSC-derived organ bud transplant. Nature, 499, 481-4. doi:
10.1038/nature12271.
Tasnim, F., Deng, R., Hu, M., Liour, S., Li, Y., Ni, M., et al. (2010). Achievements and challenges in
bioartificial kidney development. Fibrogenesis Tissue Repair, 3, 14. doi: 10.1186/1755-1536-3-14.
Transparency Market Research “Stem Cells Market (Adult, Human Embryonic, Induced
Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture)
- Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 - 2018” 2013. http://
www.transparencymarketresearch.com/stem-cells-market.html
Uygun, B.E. and Yarmush, M.L. (2013). Engineered liver for transplantation. Curr Opin Biotechnol,
24, 893-9. doi: 10.1016/j.copbio.2013.05.008.
Wu, P., Wu, X., Jiang, T.X., Elsey, R.M., Temple, B.L., Divers, S.J., et al. (2013). Specialized stem cell
niche enables repetitive renewal of alligator teeth. Proc Natl Acad Sci U S A, 110, E2009-18. doi:
10.1073/pnas.1213202110.
Yong, E. (2013). Lab-grown kidneys transplanted into rats. Engineered organs produce urine,
though not as efficiently as natural ones. Nature. Retrieved from http://www.nature.com/news/
lab-grown-kidneys-transplanted-into-rats-1.12791.
Zhavoronkov A., Litovchenko M., “Biomedical Progress Rates as New Parameters for Models of
Economic Growth in Developed Countries,” International Journal of Environmental Research and
Public Health. 2013; 10(11):5936-5952.
Zhavoronkov, A., Debonneuil, E., Mirza, N., & Artyuhov, I., “Evaluating the impact of recent advances
in biomedical sciences and the possible mortality decreases on the future of health care and
Social Security in the United States,” Pensions: An International Journal. 2012; 17(4), 241-251.
Zhavoronkov A., Cantor CR., “From Personalized Medicine to Personalized Science: uniting science
and medicine for patient-driven, goal-oriented research,” Rejuvenation Research. 2014; 16(5), 414-
418. doi:10.1089/rej.2013.1471
102
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Zhavoronkov A, Buzdin AA, Garazha AV, Borissov NM and Moskalev AA (2014), “Signaling pathway
cloud regulation for in silico screening and ranking of the potential geroprotective drugs,” Front.
Genet. 5:49. doi: 10.3389/fgene.2014.00049.
URL References
URL Ref. 1: http://alliancerm.org/
URL Ref. 2: http://www.ibisworld.com/industry/contract-research-organizations.html
URL Ref. 3: http://www.anikatherapeutics.com/products/dermal/index.html
URL Ref. 4: http://www.olympusamerica.com/seg_section/seg_presscenter_headline.
asp?pressNo=750
URL Ref. 5: http://www.genetherapynet.com/clinical-trials.html
URL Ref. 6: http://history.nih.gov/exhibits/genetics/sect4.htm
URL Ref. 7: http://www.fundingtrends.org/?keywords=gene+therapy
URL Ref. 8: http://www.fundingtrends.org/?keywords=+growth+factors%2c+small+molecules
URL Ref. 9: http://www.fundingtrends.org/?keywords=embryonic+stem+cells
URL Ref. 10: http://www.who.int/cardiovascular_diseases/en/
URL Ref. 11: http://alliamcerm.org/disease/cardiovascualr-and-regenerative=medicine
URL Ref. 12: http://www.tengion.com/pipeline/kidneys.cfm
URL Ref. 13: http://www.ipscell.com/
URL Ref. 14: http://www.hw.ac.uk/news-events/news/printed-human-organs-testing-
transplantation-11075.htm
URL Ref. 15: http://www.nydailynews.com/life-style/health/lifelike-ears-created-3d-printing-
article-11270161#ixzz2ip1ENiCk
URL Ref. 16: www.wakehealth.edu/Research/WFIRM/Research/Military-Applications/Printing-
Skin-Cells-On-Burn-Wounds.htm
URL Ref. 17: http://www.chinadaily.com.cn/business/2013-08/15/content_16895070.htm
URL Ref. 18: http://www.theguardian.com/technology/2013/jul/17/3d-printed-organs-money
URL Ref. 19: http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-
cost-of-inventing-new-drugs/
URL Ref. 20: http://www.fool.com/investing/general/2013/10/24/organovos-3-biggest-
opportunities-in-3-d-bioprinti.aspx
URL Ref. 21: http://www.houstonsportsdoctor.com/blog/wp-content/uploads/2013/12/165967.
pdf
URL Ref. 22: http://m.ajs.sagepub.com/content/early/2013/07/03/0363546513494359.abstract
URL Ref. 23: http://www.ncbi.nlm.nih.gov/pubmed/23327604
103
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
URL Ref. 24: http://www.stratatechcorp.com/news/20130116.php
URL Ref. 25: http://www.gamida-cell.com/press_item.asp?ID=54&t=Gamida-Cell%E2%80%99s-
NiCord%C2%AE-Demonstrates-Successful-Engraftment-in-Patients-with-Hematological-
Malignancies-in-Phase-I/II-Study
URL Ref. 26: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1795147&highlight
URL Ref. 27: http://www.brainstorm-cell.com/index.php/news-a-events/company-news/249-
march-21-2013
URL Ref. 28: http://www.reneuron.com/the-pisces-clinical-trial-in-disabled-stroke-patients
URL Ref. 29: http://finance.yahoo.com/news/dcprime-phase-iia-trial-dendritic-085100142.html
URL Ref. 30: http://www.stempeutics.com/pdf/Gupta.pdf
URL Ref. 31: http://www.citospin.com/news/News_index.html
URL Ref. 32: http://www.tianhecell.com/uploads/BMCMedicineT2DM.pdf
URL Ref. 33: http://www.stemedica.com/info/allogeneic-adult-stem-cells/stem-cell-
clinical-trials/2013-07-10-Stemedica-Advances-To-Phase-II-Stroke-Trial-With-Lead-Product-
Stemedyne-MSC.asp
URL Ref. 34: http://www.kiadis.com/news_1109201301.html
URL Ref. 35: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1856196&highlight
URL Ref. 36: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1798657&highlight
URL Ref. 37: http://ir.cytori.com/investor-relations/News/news-details/2012/Investigator-
Sponsored-Cell-Therapy-Clinical-Study-for-Scleroderma-Initiated-in-France1131556/default.aspx
URL Ref. 38: http://www.bioheartinc.com/assets/press/ANGELTRIALphaseIpreliminaryresults.
pdf
URL Ref. 39: http://www.celladon.net/media-center/press-release/113-press-release-
sep-26-2013
URL Ref. 40: http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-
newsArticle&ID=1866312&highlight
URL Ref. 41: http://newsroom.tissueregenix.com/tissue-regenix-announces-publication-of-
results-of-dermapure-human-decellularised-dermis-uk-trial-in-leading-wound-care/
URL Ref. 42: http://www.lctglobal.com/html/blob.php/131101%20%20DIA09%20results%20Final.
pdf?attach=0&documentCode=5175&elementId=20084
URL Ref. 43: http://www.cellbiomedgroup.com/news-details.php?nid=29
URL Ref. 44: http://www.biomup.com/file/0315/biom-up-221113-cova-card-dr-henaine-en.pdf
URL Ref. 45: http://ir.ziopharm.com/releasedetail.cfm?ReleaseID=768480
104
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
URL Ref. 46: http://ir.ziopharm.com/releasedetail.cfm?ReleaseID=812377
URL Ref. 47: http://www.mologen.com/en/detailansicht/article/mologen-ag-treatment-phase-
of-safety-trial-with-mgn1703-in-the-us-completed.html
URL Ref. 48: http://targazyme.com/america-stem-cell-inc-changes-its-name-to-targazyme-inc/
URL Ref. 49: http://www.californiastemcell.com/releases/california-stem-cell-announces-
completion-of-phase-i-cancer-stem-cell-clinical-trial-for-hepatocellular-carcinoma/
URL Ref. 50: http://ir.mesoblast.com/FormBuilder/_Resource/_module/
XOtYkoS3aU6NfWr9KEt3hw/file/Mesoblast-Corporate-Summary_Nov_2013.pdf
URL Ref. 51: http://finance.yahoo.com/news/biolinerx-enrolls-first-patient-phase-110000987.html
URL Ref. 52: http://www.transgene.fr/index.php?option=com_press_release&task=download&id=2
27&l=en
URL Ref. 53: http://link.springer.com/article/10.1007%2Fs00262-013-1457-z
URL Ref. 54: http://www.oxfordbiomedica.co.uk/press-releases/oxford-biomedica-announces-
publication-of-trovax-r-phase-ii-analyses-in-peer-reviewed-medical-journal/
URL Ref. 55: http://www.transgene.fr/index.php?option=com_press_release&task=download&id=2
36&l=en
URL Ref. 56: http://www.biocardia.com/news/pr_11_18_13.shtml
URL Ref. 57: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1878025&highlight
URL Ref. 58: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1856792&highlight
URL Ref. 59: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1839488&highlight
URL Ref. 60: http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-
newsArticle&ID=1832118&highlight
URL Ref. 61: http://www.mesoblast.com
URL Ref. 62: http://globenewswire.com/news-release/2013/12/12/596473/10061202/en/
Integra-LifeSciences-Announces-NeuraGen-R-Clinical-Study-Published-in-Journal-of-Hand-
Surgery.html?f=22&fvtc=7
URL Ref. 63: http://www.osiris.com/pdf/2013-12-18_OWM%20Publication.pdf
URL Ref. 64: http://www.gamida-cell.com/press_item.asp?ID=55&t=Gamida-Cell-Reports-
StemEx%C2%AE-Phase-II/III-Study-Safety-and-Efficacy-Data-
URL Ref. 65: http://www.gamida-cell.com/press_item.asp?ID=53&t=Gamida-Cell%E2%80%99s-
StemEx%C2%AE-Achieves-Primary-Endpoint-in-Phase-II/III-Clinical-Study
URL Ref. 66: http://news.merck.de/N/0/D5B1D4EBB19B1A78C1257B6C004F8BB3/$File/
AscoStartSeronoEnglish.pdf
URL Ref. 67: http://www.oncothyreon.com/clinical/Tecemotide.html
105
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
URL Ref. 68: http://www.gsk.com/media/press-releases/2013/gsk-and-prosensa-announce-
primary-endpoint-not-met-in-phase-iii-.html
URL Ref. 69: http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/
BiologicalApprovalsbyYear/ucm338259.htm
URL Ref. 70: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/
DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm374231.htm
URL Ref. 71: http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/
general_content_000504.jsp&mid=WC0b01ac058050f347
URL Ref. 72: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/
human/002513/WC500144937.pdf
106
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5
Investing in
Regenerative Medicine:
Technology Analysis and
Market Outlook
2014 Report #1
www.aginganalytics.com
107
Investing in Regenerative Medicine: Technology Analysis and Market Outlook 2014 Report ISBN # 978-0-9912902-1-5