3. 1
Letter from the Chairman
2014: What a year to be in the Regenerative Medicine
space. The field has matured and we believe is now
“ready for prime time.” From the wide variety of
companies developing innovative medicines and the
creation of numerous support and services companies,
to the range of indications being researched, to the
number of IPOs and major investments in the past
12 months, it is clear that at this point regenerative
medicine has reached a level of critical mass.
Every year we see compounded successes in the
field, and the Alliance for Regenerative Medicine’s
(ARM) Industry Annual Report covers many of these
accomplishments. This year will see some exciting
developments for the field, a few of which I’d like to
highlight here. ARM is actively tracking more than 400 of
these companies and many are featured in this Report.
It’s estimated that there are now more than 700
companies worldwide with a tangible regenerative
medicine focus, ranging from divisions of multinational
corporations, to smaller firms focused on niche
products or platform technologies.
Cell-based therapies represent the most mature
sub-sector of regenerative medicine, and at this
point, hundreds of thousands of patients around the
world have been treated with these therapies. As
the standard-of-care has now evolved to include FDA-
approved cell therapies, new frontiers are also opening.
Exciting breakthroughs in cell-based immune therapy
and gene therapy have opened new avenues to
transform patient care.
2014 is also a big year for regenerative medicine clinical
milestones. Starting on page 9, this report highlights the
major anticipated clinical events of this year.
ARM has also surveyed our colleagues in the
pharmaceutical industry, to gauge the level of interest
and support Big Pharma has for supporting and
developing regenerative medicines. We are pleased
to feature the results of ARM’s Pharma Survey,
demonstrating the increasing level of investment and
activity, starting on page 24.
In March, we were thrilled to see the culmination of
many years of effort, when U.S. Senators Barbara Boxer
(D-CA) and Mark Kirk (R-IL) introduced the Regenerative
Medicine Promotion Act to help accelerate the discovery
and development of new regenerative medicines.
Government regulation can play an important role
in either fostering or impairing innovation. We need
to promote a rigorous, yet efficient and transparent,
CBER regulatory process for cell-based therapies. We
also need to advocate for value-based health policy;
otherwise we will likely see short-sighted decisions
based only around cost controls vs. value creation.
The promise of our field is to deliver cost-effective, life-
saving or life-enhancing medicines which target the
underlying disease, rather than the symptoms. We must
ensure that healthcare reform prizes proven innovation,
and ultimately changes patients’ lives.
This Report is a terrific resource for those who would
like to explain our field in more detail. So let’s dive in to
2014 and learn more about what is on the horizon.
Geoff MacKay
Chairman, Alliance for Regenerative Medicine
President and CEO, Organogenesis Inc.
4. 268
North
America
100
Europe
39
Asia
11
Australia &
New Zealand
Global Breakdown of
418 Leading Companies
2
ARM’s Definition of Regenerative Medicine
Regenerative medicine research translates fundamental knowledge in biology,
chemistry and physics into materials, devices, systems and a variety of therapeutic
strategies, which augment, repair, replace or regenerate organs and tissue.
These therapies represents a new paradigm in human health with the potential to
resolve unmet medical needs through technologies that are specifically developed
to modify diseases and enable tissue regeneration or replacement. This includes
cells, biologics, genes or drugs controlling pathways related to disease causation in
addition to regulating tissue regeneration, as well as synthetic or natural scaffolds for
tissue engineering.
Regenerative Medicine Industry 2014
It’s estimated that there are more than 700 companies worldwide with a regenerative
medicine focus ranging from divisions of multinational corporations to smaller firms
focused on niche products or platform technologies. The Alliance for Regenerative
Medicine (ARM) is actively tracking 418 of these leading companies. This report covers
the clinical activity and trends of 247 therapeutically-focused regenerative medicine
and advanced therapy companies developing cell therapies, gene therapies and gene-
modified cellular therapies.
5. Cell Therapies
Primary cell-based therapies represent the most mature sub-sector of
regenerative medicine. These therapies are composed of terminally
differentiated adult cells isolated directly from human tissue including
fibroblasts, keratinocytes, chondrocytes, osteoblasts, myocytes, hepatocytes,
leukocytes, lymphocytes and endothelial cells, to name a few.
Stem cell and progenitor cell therapies represent the largest therapeutic
sub-sector of the regenerative medicine industry. These therapies are based
on a variety of different stem cell types including hematopoietic stem cells,
mesechymal stem cells, neural stem cells, epithelial stem cells, embryonic
stem cells and more recently, induced pluripotent stem cells.
First generation cell-based immunotherapy products are based on interleukins,
cytokines, chemokines, etc., but an emerging class are cell-based immuno
therapies that employ lymphocytes, macrophages, dendritic cells, T-cells, natural
killer cells and cytotoxic T lymphocytes. Some are autologous, while others
are allogeneic, and many are being genetically modified to induce the desired
immune response.
Gene Therapies
Gene therapies address defective or mutated genes needing either correction or
improved regulation through the insertion of properly functioning or genetically
altered genes into a patient’s cells. The largest segment of gene therapies
targets cancer, however regenerative-focused gene therapies are being
developed for HIV and other infectious diseases, ocular disease, cardiovascular
disease as well as several monogenic diseases.
56%
Therapeutics
& Devices
19%
Tools
13%
Banks
12%
Services
3
The majority of regenerative medicine companies are therapeutically focused and
developing a variety of technologies including cell-based therapies, small molecule
and biologic based therapies, gene therapies, tissue-engineered biomaterials
and scaffolds and implantable devices. The second largest group of regenerative
medicine companies are developing tools such as stem cells for drug discovery
and toxicity testing, as well as clinical tools, bioprocessing tools and platforms
that include equipment, consumables, reagents and storage systems to support
commercialization and clinical applications. The field also incorporates a variety
of service companies specializing in clinical trial management, manufacturing,
characterization, engineering and quality control, among others. For the purpose
of this report we will concentrate on two therapeutic pillars where the majority of
clinical activity is occurring—cell and gene therapies.
Company Breakdown by Industry Sectors
7. Other
Respiratory
Hematology
Genitourinary Disorders
Immunology
Inflammation
Gastroenterology
Infectious Disease
Ophthalmology
Endocrine,
Metabolic Genetic
Musculoskeletal
Central
Nervous
System
Dermatology
Cardiovascular
Oncology64
63
18
101
32
36
35
14
23
27
9
13
9
14
67
38
23
19
19
16
15
14
9
7
5
5
2
2
Approved/Marketed Products
38%
Dermatology
30%
Musculoskeletal
4% Oncology
4% Cardiovascular
4% Ophthalmology
8%
Immunology
Inflammation
12%
Other
Preclinical Phase I
Number of Industry-
Sponsored Trials by Phase
Phase II III
5
Regenerative Medicine and Advanced Therapy
Clinical Breakdown by Therapeutic Areas
8. 45
Companies
70
Unique
Products
17
Marketed
Products
Primary Cell-Based
Therapeutic Companies
Ophthalmology
Hematology
Ear Diseases
Central Nervous System
Respiratory
Dental
Genitourinary Disorders
Gastroenterology
Cardiovascular
Oncology
Musculoskeletal
Endocrine, Metabolic Genetic Disorders
Dermatology8
2
6
2
13
1
1
0
0
10
1
1
1
18
7
6
5
3
3
3
2
1
0
0
0
0
Preclinical Phase I
Number of Industry-
Sponsored Trials by Phase
Phase II III
6
35
35
14
10
PRECLINICAL
PHASE I
PHASE II
PHASE III
94
Trials
9. Company Product Indication
Avita Medical ReCell Dermatology
BioD BioDFence Surgical Protection
BioD BioDFactor Wound Healing
Educell d.o.o. UroArt Vesicoureteral Reflux
Fibrocell Science azficel-T Dermatology
Genzyme, a Sanofi Company Carticel, Carticel Plus Cartilage Defects
Genzyme, a Sanofi Company Epicel Burns
MacroCure CureXcell Wound Healing
MiMedx Group, Inc. EpiFix Wound Healing
Organogenesis Inc. Dermagraft Diabetic Foot Ulcer
Organogenesis Inc. Gintuit Mucogingival Conditions
Organogenesis Inc. Apligraf Diabetic Foot Ulcer
Orthofix Trinity ELITE/Trinity Evolution Musculoskeletal Defects
Osiris Therapeutics Grafix Wound Healing
TETEC Tissue Engineering
Technologies
Novocart Inject, Novocart 3D,
Novocart Disc
Cartilage Defects
TiGenix NV ChondroCelect Cartilage Defects
A Sampling of Commercial Primary Cell Therapy
and Allograft Products
Therapeutic Breakdown of Commercially Available Primary
Cell Therapies and Allograft Products
40%
Dermatology
28%
Musculoskeletal 16%
Surgical
Dental
Other
8%
8%
7
10. 91
Companies
154
Unique
Products
9
Marketed
Products
Stem and Progenitor Cell-Based
Companies and Products
65%
Allogeneic
35%
Autologous
Percent of autologous vs.
allogeneic stem and progenitor
cell-based products
Other
Respiratory
Hematology
Genitourinary Disorders
Dermatology
Surgery
Radiation Injury
Ophthalmology
Oncology
Immunology Inflammation
Gastroenterology
Endocrine, Metabolic Genetic Disorders
Central
Nervous
System
Musculoskeletal
Cardiovascular35
15
61
21
12
10
10
17
6
0
4
4
4
6
5
25
13
9
6
6
5
4
3
2
2
1
1
1
1
0
Preclinical Phase I
Number of Industry-
Sponsored Trials by Phase
Phase II III
8
177
69
PRECLINICAL
PHASE I 32
PHASE II
PHASE III: 11
289
Trials
11. Company Product Indication
Expected
Filing Date
NeoStem VSELs Periodontitis 2Q14
ViaCyte, Inc. VC-01 Insulin-Dependent Diabetes Mellitus 3Q14
ReNeuron Group plc ReN003 Retinitis Pigmentosa 3Q14
International Stem Cell
Corporation
human parthenogenetic
stem cells
Parkinson's Disease 3Q14
NeoStem AMR-001 Congestive Heart Failure 4Q14
Q Therapeutics Q-Cells Amyotrophic Lateral Sclerosis 4Q14
A Sampling of IND Filings Expected in 2014
9
A Sampling of Trials with Expected 2014 Clinical Readouts
Company Product Indication Milestone
Estimated
Date
Athersys, Inc. MultiStem Ulcerative Colitis Phase II trial result 2Q14
Athersys, Inc. MultiStem Ischemic Stroke Preliminary Phase II trial result 2Q14
Cytomedix ALD-401 Ischemic Stroke Phase II trial result 2Q14
Cytori Therapeutics, Inc. ADRCs Ischemia Phase II trial result 2Q14
Kiadis Pharma ATIR
Hematological
Malignancies
Phase II trial result 2Q14
Neuralstem Inc. NSI-566
Amyotrophic Lateral
Sclerosis
Phase II trial result 2Q14
NeoStem AMR-001 Myocardial Infarction Phase II trial result 3Q14
StemCells, Inc. HuCNS-SC Spinal Cord Injuries Additional Phase I/II trial result 3Q14
ReNeuron Group plc ReN009 Critical Limb Ischemia Phase I trial result 4Q14
StemCells, Inc. HuCNS-SC
Dry Age-Related
Macular Degeneration
Preliminary Phase I/II trial result 4Q14
Tengion, Inc.
Neo-Kidney
Augment
Chronic Kidney Failure Preliminary Phase I trial result 4Q14
TiGenix NV Cx601 Perianal Fistula Final Phase III trial result 4Q14
12. 10
42
Companies
137
Unique
Products
1
Marketed
Products
Cell-Based Immunotherapy
Companies
Company Product Indication Milestone
Estimated
Date
Prima BioMed CVac-CAN-003 Ovarian Cancer Final Phase II trial analysis 2Q14
Northwest
Biotherapeutics, Inc.
DCVax-Direct Solid Tumors Phase I/II trial result 2Q14
Immunocellular
Therapeutics, Ltd.
ICT-107
Glioblastoma
Multiforme
Additional Phase II trial result 3Q14
Argos Therapeutics, Inc. AGS-004
Human
Immunodeficiency
Virus Infection
Phase IIb trial result 3Q14
Northwest
Biotherapeutics, Inc.
DCVax-L
Glioblastoma
Multiforme
Phase III trial result 4Q14
Adaptimmune Limited NY-ESO-1/LAGE-1 Multiple Myeloma Final Phase I/II trial analysis 4Q14
A Sampling of Trials with Expected 2014 Clinical Readouts
77
54
PRECLINICAL
PHASE I
PHASE II
PHASEIII
30
12
173
Trials
Endocrine, Metabolic Genetic Disorders
Central Nervous System
Immunology Inflammation
Gastroenterology
Infectious Diseases
Oncology72
10
9
12
2
2
56
5
2
2
1
0
Preclinical Phase I
Number of Industry-
Sponsored Trials by Phase
Phase II III
13. Company Product Indication Milestone
Estimated
Date
uniQure NV Glybera Hyperlipoproteinemia European Launch 3Q14
Taxus Cardium Generx Ischemic Heart Diseases Phase III trial analysis 3Q14
Juventas Therapeutics JVS-100 Cardiovascular Failure Phase II trial result 4Q14
Juventas Therapeutics JVS-100 Critical Limb Ischemia Phase II trial result 4Q14
A Sampling of Trials with Expected 2014 Clinical Readouts
11
69
Companies
105
Unique
Products
1
Approved
Product:
uniQure’s Glybera
Gene Therapy Companies
80
37
PRECLINICAL
PHASE I
PHASE II
PHASE III: 6
20
143
Trials
16
10
3
4
18
17
14
5
7
3
3
19
6
4
4
3
2
2
2
1
0
0
Immunology Inflammation
Gastroenterology
Hematology
Musculoskeletal
Endocrine, Metabolic
Genetic Disorders
Central Nervous
System
Ophthalmology
Infectious Diseases
Dermatology
Cardiovascular
Oncology
Preclinical Phase I
Number of Industry-
Sponsored Trials by Phase
Phase II III
14. 12
Regenerative Medicine and Advanced Therapy
Clinical Trial Breakdown by
Therapeutic Catagory
Company Product / Indication Phase I Phase II Phase III
Musculoskeletal
Bone Therapeutics SA PREOB / Avascular Necrosis, Bone Fracture
CellCoTec INSTRUCT / Articular Cartilage Lesion of the Knee
Cellular Biomedicine Group ReJoin / Osteoarthritis
Co.don AG
co.don chondrosphere /
Articular Cartilage Lesion of the Femoral Condyle
Cytori Therapeutics, Inc. ADRCs / Hamstring Injury
DePuy Mitek, Inc. CAIS / Defect of Articular Cartilage
Histogenics NeoCart / Articular Cartilage Damage
ISTO Technologies DeNovoET / Articular Cartilage Damage
ISTO Technologies NuQu / Degenerative Disc Disease
Mesoblast Ltd. MPCs / Spinal Fusion
Mesoblast Ltd. MPCs / Intervertebral Disc Repair
Pluristem Therapeutics Inc. PLX-PAD / Muscle Injury
RepliCel RCT01 / Achilles Tendonitis
Tissue Engineering
Technologies AG
Novocart Disc Plus /
Lumbar Degenerative Disc Disease
TissueGene, Inc. TissueGene-C / Degenerative Arthritis
TissueGene, Inc. TissueGene-C / Knee Osteoarthritis
A sampling of cell and gene therapy companies in clinical stages of development
Musculoskeletal-related conditions in the U.S. account for
132 million visits to physicians’ offices, 29 million visits to emergency rooms,
15 million hospital outpatient visits and cost over $850 billion each year.
Further, musculoskeletal injuries in the U.S. cause workers to miss more than
440 million days of work annually.
Source: Penn Center for Musculoskeletal Disorders, Overview of the Penn Center for Musculoskeletal Disorders,
Perelman School of Medicine website, http://www.med.upenn.edu/pcmd/overview.shtml
15. 13
Company Product / Indication Phase I Phase II Phase III
Amorcyte/NeoStem AMR001 / Myocardial Infarction
Athersys, Inc. MultiStem / Myocardial Infarction
Bioheart, Inc. LipiCell / Congestive Heart Failure
Bioheart, Inc. MyoCell / Congestive Heart Failure
Capricor Therapeutics, Inc. CAP1002 / Myocardial Infarction
Capricor Therapeutics, Inc. CAP1001 / Myocardial Infarction
Cardio3 BioSciences C3BS-CQR-1 / Heart Failure
Celgene Corporation PDA002 / Peripheral Arterial Disease
Cytomedix ALD201 / Ischemic Heart Diseases
Cytomedix ALD301 / Critical Limb Ischemia
Cytomedix ALD301 / Intermittent Claudication
Cytori Therapeutics, Inc. ADRCs / Myocardial Infarction
Cytori Therapeutics, Inc. ADRCs / Ischemia
Harvest Technologies Corp. BMAC / Critical Limb Ischemia
Juventas Therapeutics JVS100 / Congestive Heart Failure
Juventas Therapeutics JVS100 / Crititcal Limb Ischemia
Mesoblast Ltd. Revascor / Congestive Heart Failure
Mesoblast Ltd. Revascor / Myocardial Infarction
Mesoblast Ltd. Autologous MPCs / Ischemia
Pharmicell Hearticellgram-AMI / Acute Myocardial Infarction
Pluristem Therapeutics Inc. PLX-PAD / Intermittent Claudication
Pluristem Therapeutics Inc. PLX-PAD / Critical Limb Ischemia
Stemedica Cell
Technologies, Inc.
Allogeneic Mesenchymal Bone Marrow Cells /
Myocardial Infarction
TotipotentRX/Cesca
Therapeutics
Autologous bone marrow derived stem cells /
Critical Limb Ischemia
TotipotentRX/Cesca
Therapeutics
Autologous bone marrow derived stem cells /
Myocardial Infarction
Cardiovascular/Vascular Disease
Between 2012 and 2030, total stroke-related costs are projected to triple,
from $71.6 billion to $184.1 billion.
Source: American Heart Association, Heart Disease and Stroke Statistics—2014 Update,
http://circ.ahajournals.org/content/129/3/e28.full#ref-726
16. 14
Company Product / Indication Phase I Phase II Phase III
Adaptimmune Limited
Autologous Genetically modified T cells /
Multiple Myeloma
Adaptimmune Limited
NY-ESO-1/LAGE-1 / Metastatic Melanoma,
Multiple Myeloma, Ovarian Cancer
Aduro Biotech
GVAX Leukemia Vaccine /
Acute Myeloid Leukemia, Chronic Myeloid Leukemia
Aduro Biotech GVAX Pancreatic Cancer Vaccine / Pancreatic Cancer
Advantagene, Inc.
AdVtk Therapy / Colon Cancer, Malignant Pleural
Effusion, Mesothelioma, Ovarian Cancer
Advantagene, Inc. AdVtk Therapy / Glioma
Advantagene, Inc. ProstAtak / Local Prostate Cancer
Advantagene, Inc. PancAtak / Locally Advanced Pancreatic Cancer
Argos Therapeutics, Inc. AGS003 / Metastatic Renal Cell Carcinoma
Argos Therapeutics, Inc. AGS005 / Chronic Lymphoid Leukemia
Argos Therapeutics, Inc. RNA-Loaded Dendritic Cell Vaccine / Melanoma
Bellicum Pharmaceuticals, Inc.
BPX101 with AP1903 /
Hormone Refractory Metastatic Prostate Cancer
Bellicum Pharmaceuticals, Inc. BPX501 / Hematological Malignancies
California Stem Cell/NeoStem
Tumor Stem Cell Specific Dendritic Cell Therapy /
Renal Cell Carcinoma
Cellerant Therapeutics, Inc. CLT008 / Cancer Chemotherapy Induced Neutropenia
Coronado Biosciences CNDO109 / Acute Myeloid Leukemia
DCPrime B.V. DCP001 / Acute Myeloid Leukemia
Dendreon Corporation Provenge / Local Prostate Cancer
Dendreon Corporation Provenge / Prostate Cancer
Erytech Pharma GRASPA / Acute Myeloid Leukemia
Fate Therapeutics ProHema / Hematological Malignancies
Gamida Cell NiCord / Hematological Malignancies
Gamida Cell StemEx / Hematological Malignancies
Glycostem Natural Killer Cells / Acute Myeloid Leukemia
Immunocellular Therapeutics, Ltd. ICT121 / Glioblastoma Multiforme
Kite Pharma
Engineered Adoptive Cell Therapy /
Non-Hodgkin’s Lymphoma
Lentigen Corporation LG723 / Melanoma
Lentigen Corporation LG740 / Hematological Malignancies
Oncology
17. 15
Company Product / Indication Phase I Phase II Phase III
Lion Biotechnologies
Contego / Breast Cancer, Colorectal Cancer,
Metastatic Melanoma, Ovarian Cancer
MolMed S.p.A. HSV-TK / Hematological Malignancies
NewLink Genetics, Inc. HyperAcute Melanoma Immunotherapy / Melanoma
NewLink Genetics, Inc.
HyperAcute Prostate Cancer Vaccine /
Hormone Refractory Prostate Cancer
NewLink Genetics, Inc.
HyperAcute Prostate Cancer Vaccine /
Metastatic Renal Cell Carcinoma
NewLink Genetics, Inc.
HyperAcute Pancreatic Cancer Vaccine /
Pancreatic Cancer
NewLink Genetics, Inc.
HyperAcute Lung Immunotherapy /
Non-small Cell Lung Cancer
Northwest Biotherapeutics, Inc. DCVax-L / Brain Cancer
Northwest Biotherapeutics, Inc. DCVax Direct / Solid Tumors
Northwest Biotherapeutics, Inc. DCVax Direct / Metastatic Colon Cancer
Northwest Biotherapeutics, Inc. DCVax L Ovarian / Metastatic Ovarian Cancer
Northwest Biotherapeutics, Inc. DCVax Prostate / Hormone Refractory Prostate Cancer
Oxford BioMedica
MetXia with Cyclophosphamide /
Breast Cancer, Melanoma, Pancreatic Cancer
Oxford BioMedica
TroVax / Colorectal Cancer, Hormone Refractory
Prostate Cancer, Mesothelioma
Oxford BioMedica TroVax / Metastatic Renal Cell Carcinoma
Sangamo BioSciences SB313 / Glioblastoma Multiforme
SOTIO
Dcvac/Pca / Hormone Refractory Metastatic Prostate
Cancer, Local Prostate Cancer, Metastatic Prostate Cancer
Tengion, Inc. Neo-Urinary Conduit / Bladder Cancer
Vical, Inc. Leuvectin / Metastatic Melanoma, Sarcomas
Oncology continued
Company Product / Indication Phase I Phase II Phase III
Infectious Diseases
Argos Therapeutics, Inc. AGS004
Calimmune Cal-1
Cell Medica Cytovir ADV
Cell Medica Cytovir CMV
Sangamo BioSciences SB-728
18. 16
Cytomedix ALD601 / Lysosomal Storage Disorders
Living Cell Technologies Limited DIABECELL / Type 1 Diabetes
Mesoblast Ltd. MPCs / Diabetic Nephropathy
Mesoblast Ltd. MPCs / Non-Insulin-Dependent Diabetes Mellitus
NeoStem Treg Program / Insulin-Dependent Diabetes Mellitus
Oxford BioMedica UshStat / Usher syndrome type 1B
Promethera Hepastem / Metabolic Disorders
Promethera Hepastem / Urea Cycle Disorder
t2cure t2c002/t2c003 / Diabetic Neuropathy
Company Product / Indication Phase I Phase II Phase III
Endocrine, Metabolic and Genetic Disorders
Diabetes affects 25.8 million people or 8.3% of the U.S. population.
Total direct and indirect medical cost for diabetes care in the U.S. as of 2007
equaled $174 billion—$116 billion of that was direct medical costs.
Source: Centers for Disease Control and Prevention, 2011 National Diabetes Fact Sheet,
Diabetes Public Health Resource, http://www.cdc.gov/diabetes/pubs/factsheet11/fastfacts.htm
Athersys, Inc. MultiStem / Ulcerative Colitis
Celgene Corporation PDA001 / Crohn’s Disease
Innovacell Biotechnologie AG ICEF15 / Fecal Incontinence
Mesoblast Ltd. Prochymal / Crohn’s Disease
TiGenix NV Cx601 / Perianal Fistula
TxCell SA OvaSave / Crohn’s Disease
Company Product / Indication Phase I Phase II Phase III
Gastroenterology
Company Product / Indication Phase I Phase II Phase III
Genitourinary Disorders
AlloCure AC607 / Acute Kidney Failure
Cook Myosite AMDC / Stress Urinary Incontinence
Cytonet Group HHLivC / Urea Cycle Disorders
Innovacell Biotechnologie AG ICES13 / Stress Urinary Incontinence
Tengion, Inc. Neo-Kidney Augment / Chronic Kidney Failure
uniQure NV/Digna Biotech AAV5-PB6D / Acute Intermittent Porphyria
19. 17
Athersys, Inc. MultiStem / Ischemic Stroke
bluebird bio Lenti-D / Adrenoleukodystrophy
BrainStorm Cell Therapeutics SC Therapy / Amyotrophic Lateral Sclerosis
Cytomedix ALD401 / Ischemic Stroke
MEDIPOST Neurostem / Alzheimer’s Disease
Neuralstem Inc. NSI567 / Spinal Cord Injuries
Neuralstem Inc. NSI566 / Amyotrophic Lateral Sclerosis
Neuralstem Inc. NSI566 / Ischemic Stroke
NsGene A/S NsG0202 / Alzheimer’s Disease
Oxford BioMedica Prosavin / Idiopathic Parkinson’s Disease
REGENX Biosciences CLN2 Gene Therapy / Batten Disease
ReNeuron Group plc ReN001 / Cerebral Ischemia
SanBio, Inc. SB623 / Ischemic Stroke
Sangamo BioSciences CERE-110 / Alzheimer’s Disease
StemCells, Inc. HuCNS-SC / Batten Disease
StemCells, Inc. HuCNS-SC / Pelizaeus-Merzbacher Disease
StemCells, Inc. HuCNS-SC / Spinal Cord Injuries
uniQure NV AAV2-GDNF / Parkinson’s Disease
Company Product / Indication Phase I Phase II Phase III
Central Nervous System
In 2012, Americans spent and estimated $200 billion
to care for those with Alzheimer’s, including $140 billion
to Medicare and Medicaid.
Unless something is done, the costs of Alzheimer’s in 2050
are estimated to total $1.1 trillion (in today’s dollars).
Costs to Medicare and Medicaid will increase nearly 500%.
Source: Alzheimer’s Association, March 2012 Fact Sheet,
https://www.alz.org/documents_custom/2012_facts_figures_fact_sheet.pdf
20. 18
Advanced Cell Technology
Retinal Pigmented Epithelial therapy /
Stargardt’s Disease
AGTC AAV2-sFLT01 / Wet Age-Related Macular Degeneration
AGTC AAVRPE65 / Leber’s Congenital Amaurosis
Avalanche Biotech AVA101 / Wet Age-Related Macular Degeneration
Neurotech NT-501 / Retinitis Pigmentosa
NightstaRx Limited AAV.REP1 / Choroideremia
Oxford BioMedica RetinoStat / Wet Age-Related Macular Degeneration
Oxford BioMedica StarGen / Stargardt’s Disease
StemCells, Inc. HuCNS-SC / Dry Age-Related Macular Degeneration
Company Product / Indication Phase I Phase II Phase III
Ophthalmology
The estimated annual total financial burden to the U.S. economy of four
major adult vision problems (AMD, cataract, diabetic retinopathy and
glaucoma), refractive errors, visual impairment and blindness is $35.4 billion.
Source: The Economic Impact of Vision Problems: The Toll of Major Adult Eye Disorders, Visual Impairment and Blindness on the
U.S. Economy, http://www.preventblindness.net/site/DocServer/Impact_of_Vision_Problems.pdf?docID=1321
(published by Prevent Blindness America, 2007)
bluebird bio LentiGlobin / Beta Thalassemia
bluebird bio LentiGlobin / Sickle Cell Anemia
Cell Medica Cytorex EBV / Lymphoma
Gamida Cell NiCord / Sickle Cell Anemia
REGENX Biosciences Factor IX Gene therapy / Hemophilia B
uniQure NV AMT060 / Hemophilia B
uniQure NV/Digna AMT021 / Acute Intermittent Porphyria
Company Product / Indication Phase I Phase II Phase III
Hematology
21. 19
Avita Medical ReCell / Burn Scar
Avita Medical ReCell / Hypertrophic Scar
Celgene Corporation PDA002 / Diabetic Foot Ulcer
Fibrocell Science azficel-T / Burn Scar
Histogen Inc. Regenica / Androgenetic Alopecia
Intercytex ProtoDerm / Skin Ulcers
Intercytex
Vavelta / Burns, Acne Scars, Contracture Scar,
Epidermolysis Bullosa, Wrinkles
Juventas Therapeutics JVS100 / Surgical Wound
MacroCure CureXcell / Diabetic Foot Ulcer
NeoStem VSELs / Wound
Stratatech Corporation StrataGraft / Burns
Taxus Cardium Genedexa / Diabetic Foot Ulcer
Company Product / Indication Phase I Phase II Phase III
Dermatology
Acorda Therapeutics Ampydin / Guillain-Barre Syndrome
Argos Therapeutics, Inc. AGS009 / Systemic Lupus Erythematosus
Athersys, Inc. MultiStem / Bone Marrow Transplantation
Athersys, Inc. MultiStem / Liver Transplantation
Cellerant Therapeutics, Inc. CLT008 / Cord Blood Transplants
Kiadis Pharma Reviroc / Bone Marrow Transplantation
Kiadis Pharma Rhitol / Graft-Versus-Host Disease
MEDIPOST Promostem / Graft-Versus-Host Disease
Mesoblast Ltd. Revascor / Bone Marrow Transplantation
Opexa Therapeutics, Inc. Tcelna / Secondary Progressive Multiple Sclerosis
Pluristem Therapeutics Inc. PLX-BMT / Bone Marrow Transplantation
TiGenix NV Cx611 / Rheumatoid Arthritis
Company Product / Indication Phase I Phase II Phase III
Immunology and Inflammation
22. 20
Regenerative Medicine Cell and Gene Therapy
Financial Performance
$4.74
Billion
Combined
Regenerative
Medicine Field
Acquisitions
Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity$737.7
$530.9
$103.2
$1,954.7
$1,116.2
$297.3
$181.3 Up Front
Dollars Raised
$437.9
Million
Primary Cell
Therapy
$11.3
0
$0.3
$347.2
$79.1 Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity
Dollars Raised
$1.872
Billion
Stem Cell and
Progenitor Cell
Therapy
$81.4
$367.3
$80.7
$855.9
$352.4
$133.8
$57.4 Up Front
Acquisitions
Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity
Dollars Raised
Financings from March 2013 to March 2014.
23. 21
Deal Type Company(s)
Total Deal
Value
Upfront
Payment
Date
Collaboration Tengion / Celgene $15M $15M 7/1/13
Merger Capricor / Nile Therapeutics NA - 7/8/13
Commercialization Agreement
uniQure NV /
Chiesi Farmaceutici
$39.8M $39.8M 7/9/13
Collaboration Stratatech / BARDA Contract $47.2M - 7/31/13
Acquisition
Mesoblast / Osiris Stem Cell
Therapeutic Business
$100M $50M 10/11/13
Licensing Deal
Cytori Therapeutics, Inc. /
Lorem Vascular
$500M $24M 11/4/13
Licensing Deal Pluristem / CHA Biotech $10.4M $10.4M 12/17/13
Acquisition Intrexon / Medistem $26M - 12/20/13
Collaboration/Licensing Deal Capricor / JJ $325M $12.5M 1/6/14
Collaboration Sangamo / Biogen Idec $320M $20M 1/9/14
Acquisition of Dermagraft Organogenesis Inc. / Shire $300M 0 1/17/14
Acquisition SillaJen / Jennerex $150M - 3/17/14
$580.7
Million
Cell-Based
Immunotherapy
$249.8
$102.4
$4.9
$110.6
$99.5
$13.5
$7.9 Up Front
Acquisitions
Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity
Dollars Raised
Noteworthy Deals and Acquisitions
$1.85
Billion
Gene
Therapy
$395.2
$61.2
$17.3
$641.0
$585.2
$150.0
$116 Up Front
Acquisitions
Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity
Dollars Raised
24. 22
03/14/13
Mesoblast Ltd.
raises $175.3M
in private
placement
05/28/2013
Jennerex
Biotherapeutics, Inc.
raises $21.6M in
private placement
06/24/2013
bluebird bio closes
$116.1M IPO
08/12/2013
Fate Therapeutics raises
$20M in private offering
07/04/13
Cardio3 BioSciences
closes $30M IPO
05/15/2013
Kite Phara raises $35M
in Series A round
07/01/2013
Tengion, Inc.
raises $18.6M
07/10/2013
ViaCyte, Inc.
raises $10.6M in
private equity
08/26/2013
Argos
Therapeutics, Inc.
raises $42.5M in
a Series E round
08/13/2013
Opexa Therapeutics, Inc.
raises $19.3M
in public offering
09/04/2013
iPierian
secures $30M
in venture
financing
06/04/2013
StemCells, Inc.
secures $30M
07/30/2013
Cellular Dynamics
International
closes $46.1M IPO
09/23/2013
Sangamo
BioSciences
raises $74.2M in
public offering
March
2013
April
2013
May
2013
June
2013
July
2013
August
2013
September
2013
A Sampling of Noteworthy Financings
March 2013 through March 2014
“We believe that regenerative
medicine is at a critical juncture—
similar to the position of monoclonal
antibodies in the mid to late 90s.”
25. 23
01/13/13
Juno Therapeutics, Inc. raises
$145M in a Series A round
02/12/13
Voyager Therapeutics
raises $45M
in Series A round
10/08/2013
StemCells, Inc.
raises $18.6M
in public
offering
10/09/2013
NeoStem raises
$40.3M in
public offering
11/20/2013
TiGenix NV raises
$16.2 million in
private placement
10/22/13
Spark Therapeutics
launches with $50M
capital commitment
12/13/2013
Stem Cell
Therapeutics
raises $31.13
in private
placement
02/27/13
Celladon
Corporation
closes $50.6M IPO
11/25/13
Editas Medicine raises
$43M in a Series A round
10/04/13
Fate Therapeutics
closes $46M IPO
11/06/2013
Lion Biotechnologies
raises $23.3M in
private placement
03/19/2014
Sangamo
BioSciences
raises $100M in
public offering
02/10/2014
uniQure NV closes
$91.8M IPO
01/10/2014
AGTC closed $50M IPO
12/12/13
MiMedix raises
$34M in public
offering
01/10/2014
Athersys, Inc. raises
$20.5M in direct offering
11/25/2013
Northwest Biotherapeutics, Inc.
raises $27M in public offering
02/20/2014
Argos Therapeutics, Inc.
closes $45M IPO
01/04/14
Bellicum
Pharmaceuticals, Inc.
raises $14.7M in
Series B Round
October
2013
November
2013
December
2013
January
2014
February
2014
March
2014
26. 24
The Alliance for Regenerative Medicine’s Science and
Technology Committee began a project in the summer
of 2013 to survey the RD, product development
and business development leadership in top pharma
and biotech companies regarding their strategic
perspectives of regenerative medicine. The primary
objective of the survey was to engage pharma and
biotech executives to speak candidly and openly about
their views of the sector—highlighting opportunities
and the therapeutic potential of the technologies while
also addressing concerns regarding major regulatory
and commercial hurdles yet to be overcome. The
summary that is provided herein is a compilation of their
responses that provides an unprecedented look into the
thought process used by large companies to evaluate
regenerative medicine opportunities.
Survey Respondents
Allergan, Amgen, Baxter, Biogen Idec, Boehringer
Ingelheim, Celgene, Eli Lilly, GSK, Johnson Johnson,
Merck Serono, Novartis, Novo Nordisk, Pfizer, Roche,
Sanofi-Genzyme, Shire
Pharmaceutical and Large-Cap
Biotechnology Survey
“Our working definition of regenerative
medicine includes a broad range of products
that leverage the body’s intrinsic abilities to
heal itself.”
“Regenerative medicine is the use of cells or
entities that stimulate cells to repair or replace
damaged tissues.”
“We define regenerative medicine broadly.
We include all technologies that are
regenerative including cells, antibodies,
gene therapies, small molecules, biologics,
biomaterials, etc. Our company also considers
stem cells for drug screening and safety
toxicology testing as regenerative medicine.
Immunotherapy is not positioned within our
regenerative medicine group.”
How Pharmaceutical and Large-Cap Biotech Companies
Define Regenerative Medicine
“Our team views ‘cell-based immunotherapy’
as regenerative medicine with a large focus
on oncology.”
“Regenerative medicine means any therapy
that will repair or restore cells and physiology
leading to improved function.”
“We view the field of regenerative medicine
in the same way ARM does. In fact, our group
was part of the team that came up with ARM’s
definition of regenerative medicine.”
“Within our venture group we don’t have a
specific definition, but from our understanding
it can include a range of technologies including
small molecules, biomaterials, cell-based
therapies and stem cells. We would also
include gene therapy.”
re•gen•er•a•tive med•i•cine
27. 25
Pharmaceutical and Large-Cap
Biotechnology Survey
The Pharmaceutical and Large-Cap Biotech
Perspective on Regenerative Medicine
“We are actively looking for a partner in the cell therapy business
and are open to any relationship from partnership to divestiture.”
“We realize it’s a frontier technology beyond a five year time horizon and
we don’t want to miss the boat. Our company is engaged in various levels and
resources are internally devoted.”
“We are engaged in the Alliance for Regenerative Medicine because we want
expertise, we want to be at the right place at the right time.”
Of the 16 pharmaceutical and large-cap biotech
companies interviewed, the detailed discussions
revealed each of them is investing in some aspect
of regenerative medicine and view the sector as
a potential paradigm shift in the development of
breakthrough medicines. One hundred percent of
the companies interviewed also indicated that they
are closely monitoring both preclinical and clinical
stage technologies and 40% of these companies are in
active pursuit of therapeutic opportunities. In addition
to having some level of investment in the industry,
a recurring message that echoed throughout each
interview is that pharma does not want to miss this
opportunity; they are monitoring the space diligently
and methodically assessing the key questions to
commercialize and bring these products to market.
Lastly, not one company representative stated that
they were not interested in this burgeoning field.
100%
Investing With
Programs Underway
100%
Monitoring
44%
Actively Pursuing
Opportunities
0%
Not Interested
Pharma and Large-Cap Biotechs
Engagement in Regenerative Medicine
28. 26
Where is Pharma Investing?
“We’re just beginning to understand the
potential for regeneration. As this unfolds the
potential for endogenous repair is
going to accelerate.”
“We are not currently interested in devices
alone. Combination products are a future
area of interest.”
“We would like to invest early, close to proof
of concept. We will continue to invest in the
areas of stem cells, gene therapy and other
regenerative medicine venture investments.”
“Our internal investment in regenerative
medicine is probably upward of
10% of the overall RD budget.”
69%
64%
56%
31%
31%
Endogenous Activation
Beyond cell-based therapies, the interviews revealed a core group of pharma and large-cap biotechs, especially
those focusing on specific neurodegerative disease indications, to have teams of cellular biologists in place studying
endogenous stem cell microenvironments. The common goal of these groups is to discover small molecules and/or
biologics that can activate dormant cells and down regulated cellular pathways, thus restoring the body’s natural ability
to regenerate certain tissues.
Gene and Gene-Modified Cell Therapies
As previously mentioned, 31% of the pharma companies interviewed expressed moderate to significant interest in gene
therapies and gene-modified cell therapies for a variety of disease indications. The highest level of interest was in the
area of monogenic disease. The companies focused on these indications saw potential for these therapies since the
mechanism of action is clear—a single nucleotide mutation resulting in the manifestation of the disease.
Cell Therapies
On the cell-based therapeutic front, 69% of the companies have already invested in cellular-based regenerative
medicine products outside their company and 31% of them had made, or were making, investments in gene-modified
cell therapy programs.
Drug Discovery
Of the interviewed companies, 88% considered the use of stem cells for disease modeling, drug discovery and
toxicology testing as regenerative medicine, and of those companies, 64% are actively working with stem cells as
key drug discovery tools. Furthermore, several of those companies mentioned that stem cells represent a paradigm
shift in drug discovery.
Combination Products
Fifty-six percent of the companies’ surveyed expressed moderate to significant interest in combination products that
include a tissue engineered scaffold/device component.
29. 27
“We view iPSCs as very important tools for
modeling monogenic diseases.”
“iPSCs for drug discovery, toxicology and
modeling is our core focus in regenerative
medicine. This technology not only enhances
drug discovery, it is a paradigm shift
in drug discovery.”
“We’re getting more used to using stem cells
for modeling and discovery. We have a group
that’s very focused on genetics and genetic
variants that cause disease. For this group
cellular models make a lot of sense.”
“Stem cells are a tremendous resource for
high-throughput screening and toxicology
testing, they allow for efficient screening and
it gets around animal models.”
“Our team is a major proponent of stem cells
for drug discovery, modeling and
toxicology studies.”
“We use iPSCs and embryonic stem cells for
modeling disease. High throughput screening
is also fantastic use for these cells.”
Pharma and Large-Cap Biotechs’ Level of Interest in Stem Cells
for Drug Discovery, Modeling and Toxicology Testing
50%
Very Important
19%
Important
13%
Neutral
6%
Somewhat
Important
6%
Not at all
Important
6%
N/A
30. 28
“The most successful products to date
have been autologous and though they
are very challenging, manufacturing costs
amongst other challenges, we think they
are very promising.”
“The most promising cell types are
allogeneic MSCs and ESCs.”
“Autologous versus allogeneic is a tough
question…historically there has been concerns
around using non-autologous systems but
proof is in the data—relatively agnostic.
Unmet medical needs are wide open for
autologous products.”
“We are working with both autologous and
allogeneic stem cells—clinical data will be
what’s most important.”
“Autologous is difficult because of logistical
challenges but at the end of the day it’s all
manageable if it can impact patients.”
“We have some concerns about autologous
therapies because of manufacturing
and logistics. But there is also concern
about allogeneic as there could be an
immune response—this seems to be
getting less risky. We will certainly look at
all different approaches.”
Autologous vs. Allogeneic Cells
as Therapeutic Modalities
The responses from the interviews were diverse and
open-minded around autologous and allogeneic cell
therapies. Very few of the companies interviewed had
a strong preference toward one model versus the other,
despite the logistical challenges and potentially higher
costs linked to patient-specific or autologous cellular
therapeutics. Of the 16 companies interviewed, 50% of
them are already investing in patient-specific autologous
cellular therapies. Investment in off-the-shelf allogeneic
cell therapies was virtually the same with 56% of the
participants declaring projects and investments under
way. The findings clearly illustrate that, for the most part,
pharma does not believe there is a dominant technology.
This was evident as 50% of the participants stated
that their company remains agnostic toward the two
therapeutic modalities.
Percent of Companies Focused on Investing or
Developing Autologous and Allogeneic Cell Therapies
Allogeneic
Autologous
Agnostic
58%
50%
50%
31. 29
“In the next 5-10 years a lot will be done here
through external partnerships. Our expertise
is regulatory, manufacturing
and commercialization, the rest will be
done with partners.”
“We have several validated programs
with academic labs. It’s important for an
independent entity to look at the data.”
“Our company is tracking stem cell
partnerships through science focus groups
and companies in areas of interest. We’ve
also in-licensed technology from universities
and we’re funding research projects at several
external academic partner laboratories.”
“Most of our effort in regenerative medicine
would be through partnerships…we want to
be working with the experts.”
How Pharma and Large-Cap Biotech
Companies Are Organized to Pursue
Regenerative Medicine
Of the four major group types, the most common
organizational structure was through vertically
integrated regenerative medicine RD units. The
interviews revealed that 69% of the companies already
have regenerative medicine focused teams established,
each with unique strategies and therapeutic targets.
External regenerative medicine partnerships were also
highly common among the participating companies.
Several of them considered partnerships a critical
component of success within the regenerative medicine
industry. Pharma generally agreed that they are not
experts in cell-based therapies and must rely on the
experts in industry and academia to successfully
co- develop regenerative medicine products.
The common message that resonated through the
majority of interviews was that pharma cannot do
this alone and will need to rely on a variety of
external partners to advance their regenerative
medicine programs.
Focused Research Development Units
Disease Teams or Therapeutic Divisions
Business Development Teams
Venture Groups
69%
44%
44%
25%
Top Four Business Strategies
Focused on external investments outside
the company’s core areas of expertise
32. 30
Where Pharma Sees
Major Therapeutic Opportunities
Here and Now Opportunities
The majority of participants, 63%, stated that regenerative
medicine technologies for wound healing are here
now and will continue to constitute the nearest term
therapeutic opportunity. Other therapeutic areas just
over the horizon included cell-based therapies for
musculoskeletal conditions, bladder and autoimmune
disorders such as GvHD and Crohn’s Disease and adoptive
T-Cell therapies to treat hematological malignancies.
Near-Term Opportunities
In the nearest-term—within the next five years—treating
cardiovascular and ischemic-related diseases with
autologous and allogeneic stem cell based technologies
received the most comments from the participants.
Interviewees also clearly identified cell and gene-based
therapies for ocular diseases, such as age-related
macular degeneration, to be a near-term opportunity
for the field. Each of the six companies engaged in this
space considered ocular disease to be a key therapeutic
opportunity for regenerative medicine and strongly
believed that these technologies will show clear clinical
efficacy and could represent a major advancement in
standard of care.
Another disease area that garnered interest of big
pharma is the monogenic disease space. Of the three
pharma companies that expressed significant interest in
monogenic disease, they each believed that this area of
regenerative medicine is a wide-open opportunity and
achievable in the near term.
Long-Term Opportunities
Neurodegenerative diseases were viewed as the greatest
longer-term opportunity for regenerative medicine,
especially as several of these indications affect millions
and treatment options are highly limited.
The 25% of companies that viewed diabetes as a major
opportunity for regenerative medicine were extremely
passionate about their reply and highly committed to the
therapeutic area. The companies interested in targeting
diabetes also stated that despite the difficulty in under-
standing the science behind the disease, they believe
that there will be a major breakthrough within the next
10 years and the opportunities to treat the disease with
regenerative therapies for beta cell replacement and
other insulin regulating mechanisms will be tremendous.
The dominant technology strategy for each of the four
companies was predominantly cell-based, testing a
variety of multipotent and pluripotent cell types, both
patient specific and off-the-shelf cell. Additionally, there
was interest expressed in regenerative gene therapies
for diabetes.
“Most promising areas of regenerative
medicine include the ischemic space/
cardiovascular, autoimmune/UC/IB/GVHD,
skin and musculoskeletal related injury
and disease.”
“In the next five years we will see progress in
the areas of oncology and cardiovascular.
The cardio space will see the most progress
in the next 10 years.”
“The disease area that holds the greatest
promise is the monogenic disease space.”
“The most promising areas for regenerative
medicine in the next 5-10 years include
cardiovascular, ischemia and immunology.”
33. 31
“We have a large effort currently taking place in gene-modified HSCs for several rare diseases.
Focusing on rare diseases allows us to test transformative platforms on small patient groups
with lower regulatory boundaries.”
“We believe that monogenic disease is where you can focus and be successful because there’s
no other therapeutic option. We can also be successful in this area because the MOA is 100%
clear. Large indications are tough because we don’t really understand the disease.”
“Mesenchymal stem cell trials for GvHD, cardiovascular and other indications will read out—
potentially transformative one way or the other. Regardless, they will definitely be safe and find
their place in medicine. The skin is where cell-based therapy is now.”
63%
56%
44%
38%
37%
32%
25%
25%
25%
19%
19%
13%
13%
Spinal Cord Injury
Stroke
Monogenic Disease
Vascular Disease
Oncology
Diabetes
Metabolic Disorders
Musculoskeletal
Cardiovascular Disease
Ocular Disease
Autoimmune
Neurodegenerative
Wound Burns
Percent of Companies that Consider the Therapeutic Area
as Highly Opportunistic for Regenerative Medicine
34. 32
Where Pharma Sees
Major Challenges
Lack of Predictable and
Clear Regulatory Guidance
Of the 10 areas of challenge examined, the lack of
predictable and clear regulatory guidance received
the lowest amount of concern from the participants—
indicating that these companies feel that regenerative
medicine products have the ability to succeed within
current regulatory constructs.
15%
8%
77%
Lack of Predictable and
Clear Regulatory Guidance
No Concern
Marginal/Moderate Concern
Significant/High Concern
“Cost of goods is a very low concern. Scientific
and technical challenges must be determined
up-front. Safety and efficacy defines the risk
benefit. Regulatory pathway defines if the
technology can be successful.”
“The key questions we’re considering are
mostly centric around business models and
regulatory pathways.”
“Disagreement amongst regulatory agencies
adds to the challenge.”
“Lack of geographic harmonization
is not a unique issue and true of all
drug development.”
Manufacturing and Scale-Up
The common message from the participants around
manufacturing and scale-up was that cell-based
therapeutics, combination products and other advanced
therapies will be more complex in manufacturing
design than current drugs, and therefore will confront
significant development challenges. However, these are
engineering questions that companies will undoubtedly
solve; similar to the way manufacturing and scale-up
challenges were solved for biotechnology products such
as proteins and antibodies in the early- to mid-1990s.
8%
46%
Manufacturing/scale up
No Concern
Marginal/Moderate Concern
Significant/High Concern 46%
“People over estimate CMC as an issue.
Although it is a significant hurdle, we believe
if the therapy shows a significant benefit and
the data is robust, companies will figure out
how to address CMC issues. Science is the
main challenge.”
“We manufacture all of our products on
our own, but we don’t have any cell therapy
manufacturing capabilities.”
35. 33
Uncertain Financing Environment
Despite the variation gathered from the quantitative
survey, the comments made throughout the interviews
were quite homogenous. Each of the 16 companies
interviewed mentioned that lack of access to capital is
causing companies to run scaled-down, inadequately
powered clinical trials with poorly understood end-
points—a major concern of pharma. Small-cap
companies struggling to run high quality clinical
trials due to lack of capital was the most frequently
mentioned concern. Several participants even men-
tioned that the science and technology behind many
of the regenerative medicine companies may, in fact,
be sound, but without well-designed trials generating
quality clinical data, it will be very difficult for pharma
to measure the opportunity and the clinical value of
these technologies. The bottom line message is that the
lack of access to capital may be forcing companies to
run poorly designed clinical trials, therefore resulting in
questionable clinical data—the single most influential
factor for pharmaceutical investment.
15%
54%
Uncertain financing environment
No Concern
Marginal/Moderate Concern
Significant/High Concern 31%
“We always focus on data and our strategy
evolves based on the data.”
Uncertain Reimbursement
Environment
Throughout the interviews, pharma consistently
mentioned that reimbursement is a challenge, but
not one specific to regenerative medicine. Companies
focusing on indications such as diabetes, incurable
neurological disorders, rare diseases or other indications
with a high level of unmet medical need displayed
less concern around reimbursement than companies
targeting therapeutic areas with higher product
competition, i.e., wound healing and orthopedic
conditions. Of the participants, 15% considered
reimbursement to be no concern or challenge; 23%
marginal concern or challenge; 23% moderate concern
or challenge and 39% considered this to be a significant
concern or challenge.
15%
46%
Uncertain reimbursement
environment
No Concern
Marginal/Moderate Concern
Significant/High Concern 39%
“Reimbursement would be layered in the
discussion very early, and more and more
so that is the case. Public perception is not
an issue. Scale-up and manufacturing is a
secondary situation.”
“Companies are going to reinvest once they see clinical success and marketed products.
Mechanism of action is important but not critical, we’ve had products on the market
without knowing the mechanism of action.”
“Government funding would help get small companies through some of the valleys. There are
lots of gaps in the preclinical work, early trial and experiments due to shoestring budgets.”
“The finance environment is very difficult. It’s causing companies
to run poor trials with poor clinical endpoints.”
36. 34
Potency Assay Validation
The quantitative survey revealed 43% of participants
found potency assay development to be a more
than moderate concern. Additionally, potency assay
validation was often the first challenge or concern
mentioned during the interviews. These top -of-mind
concerns may mirror where we are as an industry, and
may be especially reflective of the clinical development
challenges facing the leading companies—many of
which are now moving past safety trials and entering
later stage efficacy and dosing trials. Potency assay
validation is a here-and-now issue and something with
which pharma is grappling with. The good news is that
no companies viewed potency assay validation as a
highly significant concern and only 23% considered
this to be a significant concern. Instead, potency assay
validation is considered to be a somewhat new and
unique issue that cell-based regenerative medicine
companies are actively facing.
8%
69%
Potency assay validation
No Concern
Marginal/Moderate Concern
Significant/High Concern23%
“Potency assay development and validation
is an issue. Cell characterization on the other
hand is getting much better with a pretty
good roadmap at this time.”
Cost of Goods
After reviewing the interviews and the quantitative
results it was evident that a fair amount of disparity
existed around the level of concern regarding cost of
goods for regenerative medicine therapies. Despite the
range of concerns, 61% of the participants responded
within the no concern to moderate concern brackets—
a positive sign for the regenerative medicine industry.
The remaining 39% viewed cost of goods to be a
significant concern.
39%
15%
46%
Cost of goods
No Concern
Marginal/Moderate Concern
Significant/High Concern
“Development costs and unproven business
models are not major concerns. Areas of high
concern include lack of standards and geo
regulatory harmonization.”
“We want to use regenerative medicine
technologies where there is clear benefit over
drugs on the market.”
“Potency assay development and validation is a concern—it’s a necessity for the end-user
and of course important from a regulatory standpoint.”
“Potency assay development and validation is also very difficult as it’s hard to say
that a given marker indicates a particular clinical outcome.”
“Dosing of cell therapies is an area of concern. Cell characterization
is not as risky as cell potency as it’s more objective.”
37. 35
Product Consistency and Standards
Results from the quantitative survey and the personal
interviews revealed that product consistency and lack of
standards is possibly the single greatest challenge facing
the field. Of the companies interviewed 92% rated this
to be area of moderate-to- significant concern. The
interviews also illustrate how young the regenerative
medicine industry still is, despite the excitement and
number of companies in the space, and that time is still
needed for the industry to mature and become more
standardized. It was mentioned by several participants
however, that the issue around standards has improved
when compared to 10 or even five years ago.
8%
46%
Product consistency/standards
No Concern
Marginal/Moderate Concern
Significant/High Concern 46%
“Lack of standards has been problematic,
but the situation is improving.”
“Areas of high concern include lack of
standards and geo regulatory harmonization.”
Clinical Adoption and
Medical Expertise
Sixty-two percent of the respondents believed that
clinical adoption and medical expertise is a marginal
to moderate concern. Of the remaining survey
participants, 15% considered clinical adoption to be of
no concern while 23% considered clinical adoption to
be significant concern. Lastly, none of the participants
considered this to be a highly significant concern.
15%
62%
Clinical adoption/medical expertise
No Concern
Marginal/Moderate Concern
Significant Concern23%
Supply Chain Logistics
Supply chain logistics were not considered to be a
significant or highly significant challenge facing the field.
In fact, the majority of participants, 77%, considered
supply chain logistics to be a moderate concern or less.
A handful of participants mentioned that shipping and
storage of cell-based therapies will be significantly more
challenging than shipping and storage of chemical and
protein-based drugs. Several participants additionally
mentioned that with recent advances in quality control
systems and the available expertise from supply chain
focused service partners, supply chain and logistical
concerns will not be a major hurdle for regenerative
medicine technologies. Regardless, supply chain logistics
is something that should not be dismissed and will be a
marginal to moderate challenge facing the field.
8%
69%
Supply chain logistics
No Concern
Marginal/Moderate Concern
Significant/High Concern23%
“Cells will be the ‘easy’ part—the engineering
and delivery will be the complex part.”
“Scalability, development costs, risk of lot
failure, unproven business models and COGs
are concerns. Other logistical challenges
include shipping conditions for live cells.”
38. 36
Membership
Regenerative MedicineRegenerative Medicine
ALLIANCEfor
Companies
Aastrom Biosciences, Inc.
Abeona Therapeutics
Advanced Cell Technology
AGTC
Akron Biotechnology
AlloCure
AlloSource
Athersys, Inc.
Avita Medical
AxoGen, Inc.
Baxter
Bell BioSystems
BioLife Solutions, Inc.
Biomatrica
Biospherix, Ltd.
BioTime, Inc.
Blood Centers of America Inc.
bluebird bio
BrainStorm Cell Therapeutics
Calimmune
Capricor Therapeutics, Inc.
Celgene Corporation
Cell Cure Neurosciences Ltd.
Cell Line Genetics, Inc.
Cell Therapy Group
CellGenix GmbH
Cellular Dynamics International
Cellular Technology Limited
Celsense Inc.
Cesca Therapeutics
Circle Biologics, Inc.
Cord Blood Registry
Clinical Trial Consulting
Cynata Therapeutics Inc.
Cytomedix
Cytori Therapeutics, Inc.
DiscGenics, Inc.
Dohmen
EMD Millipore Corporation
Fate Therapeutics
Fibrocell Science
Fisher BioServices
GE Healthcare
GenVec
Global BioTherapeutics
Harvard Apparatus
Regenerative Technology
HemoGenix
Histogen Inc.
Histogenics
Humacyte, Inc.
Invetech
InvivoSciences, Inc.
iPierian Inc.
ISTO Technologies
Johnson Johnson
Juventas Therapeutics
Lonza Group Ltd.
MaxCyte, Inc.
Medpace
Mesoblast Ltd.
MiMedx Group, Inc.
Minerva Biotechnologies
Corporation
Nanofiber Solutions
NeoStem
Northwest Biotherapeutics, Inc.
Organogenesis Inc.
Organovo Holdings, Inc.
OrthoCyte Corp.
Osiris Therapeutics
Oxford BioMedica
Pfizer Inc.
Pluristem Therapeutics Inc.
Progenitor Cell Therapy
Q Therapeutics
Regeneus Ltd.
Reglera
RepliCel
RhinoCyte Inc.
Rossi Group Consulting
RxGen
Sangamo BioSciences
Sanofi-Genzyme
Sartorius AG
Shire
SironRX Therapeutics
Smith Nephew
StemBioSys
StemCells, Inc.
Tengion, Inc.
TERUMO BCT, Inc.
Thermo Fisher Scientific
Tissue Banks International
39. 37
TissueGene, Inc.
Tissue Genesis, Inc.
TrakCel Ltd.
Vet-Stem, Inc.
ViaCyte, Inc.
Investors
Asset Management Ventures
Kentucky Seed Capital Fund
Novitas Capital
Toucan Capital
Triathlon Medical Ventures
Patient Advocates/
Foundations/Associations
Association of Clinical
Research Organizations
Alpha-1 Foundation
ALS Association
American Association for
Dental Research
BioBridge Global
California Institute for
Regenerative Medicine
Californians 4 Cures
Cell Society
Centre for Commercialization
of Regenerative Medicine
Friends of Cancer Research
Genetics Policy Institute
Human Organ Project, Inc.
International Society for
Stem Cell Research
JDRF
Missouri Cures
National Disease
Research Interchange
National Multiple Sclerosis Society
National Stem Cell Foundation
Nebraska Coalition for
Lifesaving Cures
New York Stem Cell Foundation
Parkinson’s Action Network
Prevent Cancer Foundation
Stop ALD Foundation
Student Society for
Stem Cell Research
Texas Cures Education Foundation
Unite 2 Fight Paralysis
Research Institutions
Cleveland Clinic
Cornell University
Johns Hopkins Translational Tissue
Engineering Center
Neural Stem Cell Institute
Northwestern University
Comprehensive Transplant Center
Pittsburgh Tissue Engineering
Initiative
Sanford-Burnham Medical
Research Institute
Texas Heart Institute
UC San Diego Stem Cell Program
University of Maryland Center
for Stem Cell Biology and
Regenerative Medicine
University of Minnesota
Stem Cell Institute
University of Utah Cell Therapy and
Regenerative Medicine Program
Affiliates
AlphaMed Press
European Affiliates
Andalusian Initiative for
Advanced Therapies
Aposcience AG
ATMI
Cardio3 BioSciences
Cell2B
CellData Services
Cell Therapy Catapult
Chemelot Campus B.V.
DCPrime B.V.
Foundation for Biomedical
Research and Innovation
Fraunhofer Institute for
Cell Therapy and Immunology
Gri-Cel, S.A.
Kiadis Pharma
K.U. Leuven
Med Cell Europe AG
Newcastle University
Novadip Biosciences SA
PharmaCell B.V.
Promethera
ReGenesys B.V. B.A.
ReNeuron Group plc
Sistemic Scotland Limited
TiGenix NV
University College London
Center for Stem Cells and
Regenerative Medicine
Voisin Consulting
