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Regenerative MedicineRegenerative MedicineALLIANCEfor
Regenerative Medicine Annual Industry Report2014
Table of Contents
Letter from the Chairman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Regenerative Medicine 2014Geographic Breakdown . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Industry Sector Breakdown . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
ClinicalRegenerative Medicine and Advanced Therapy Clinical Overview . . . . . . 4
Primary Cell-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Stem and Progenitor Cell-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Cell-Based Immunotherapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Gene Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Clinical Breakdown by Therapeutic Category . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Finance Regenerative Medicine Cell and Gene Therapy Financial Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Noteworthy Deals and Acquisitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Noteworthy Financings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Pharma and Large-Cap Biotech Survey The Pharmaceutical and Large-Cap Biotech Perspective on Regenerative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Where is Pharma Investing? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Autologous vs. Allogeneic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
How Pharma and Large-Cap Biotechs are Organized to Pursue Regenerative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Where Pharma Sees Major Therapeutic Opportunities . . . . . . . . . . . . . . . . . 30
Where Pharma Sees the Major Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
ARM Membership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Information in this report is from March 2013 through March 2014.
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.
268North
America
100Europe
56%Therapeutics
& Devices 19%Tools
13%Banks
12%Services
39Asia
11Australia &
New Zealand
Global Breakdown of 418 Leading Companies
2
ARM’s Definition of Regenerative MedicineRegenerative 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.
Cell TherapiesPrimary 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 TherapiesGene 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.
268North
America
100Europe
56%Therapeutics
& Devices 19%Tools
13%Banks
12%Services
39Asia
11Australia &
New Zealand
Global Breakdown of 418 Leading Companies
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
Cell-Based Immunotherapies
Primary Cell-Based Therapeutics
Stem Cell and Progenitor Cell-Based Therapeutics
Gene Therapies
4
Regenerative Medicine and Advanced Therapy Overview
247Total
TherapeuticCOMPANIES
466Total UniqueTherapeuticPRODUCTS
699Total Preclinical & Clinical Stage
TRIALS
91Companies
69 Companies
45 Companies
42 Companies
154 Unique Products
105 Unique Products
70 Unique Products
137 Unique Products
9 Marketed Products
1 Approved Product
17 Marketed Products
1 Marketed Product
289Trials
143Trials
94Trials
173Trials
uniQure’s Glybera
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% Oncology4% Cardiovascular4% 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
45Companies
70Unique
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 III94Trials
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
91Companies
154Unique
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
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
10
42Companies
137Unique
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-004Human 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
PHASE III
30
12173
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
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
69Companies
105Unique
Products
1 Approved
Product:uniQure’s Glybera
Gene Therapy Companies
80
37
PRECLINICAL
PHASE I
PHASE II
PHASE III: 6
20
143Trials
16
10
3
4
18
17
14
5
7
3
3
19
6
4
4
3
2
2
2
1
0
0Immunology & 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
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 AGco.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
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
14
Company Product / Indication Phase I Phase II Phase III
Adaptimmune LimitedAutologous Genetically modified T cells / Multiple Myeloma
Adaptimmune LimitedNY-ESO-1/LAGE-1 / Metastatic Melanoma, Multiple Myeloma, Ovarian Cancer
Aduro BiotechGVAX 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/NeoStemTumor 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 PharmaEngineered Adoptive Cell Therapy / Non-Hodgkin’s Lymphoma
Lentigen Corporation LG723 / Melanoma
Lentigen Corporation LG740 / Hematological Malignancies
Oncology
15
Company Product / Indication Phase I Phase II Phase III
Lion BiotechnologiesContego / 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 BioMedicaMetXia with Cyclophosphamide / Breast Cancer, Melanoma, Pancreatic Cancer
Oxford BioMedicaTroVax / Colorectal Cancer, Hormone Refractory Prostate Cancer, Mesothelioma
Oxford BioMedica TroVax / Metastatic Renal Cell Carcinoma
Sangamo BioSciences SB313 / Glioblastoma Multiforme
SOTIODcvac/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
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
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
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
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
IntercytexVavelta / 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
20
Regenerative Medicine Cell and Gene Therapy Financial Performance
$4.74Billion
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
$437.9Million
Primary Cell Therapy
$11.3
0
$0.3
$347.2
$79.1 Public Offerings
Partnerships
Grants
PIPES
Venture Capital and Private Equity
Dollars Raised
$1.872Billion
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.
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 / J&J $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
$580.7Million
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
$1.85Billion
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
22
01/13/13Juno Therapeutics, Inc. raises
$145M in a Series A round
02/12/13Voyager Therapeutics
raises $45M in Series A round
03/14/13Mesoblast Ltd. raises $175.3M
in private placement
05/28/2013Jennerex
Biotherapeutics, Inc. raises $21.6M in
private placement
06/24/2013bluebird bio closes
$116.1M IPO
08/12/2013Fate Therapeutics raises $20M in private offering
10/08/2013StemCells, Inc. raises $18.6M
in public offering
10/09/2013NeoStem raises
$40.3M in public offering
11/20/2013TiGenix NV raises
$16.2 million in private placement
10/22/13Spark Therapeutics launches with $50M capital commitment
12/13/2013Stem Cell
Therapeutics raises $31.13
in private placement
07/04/13Cardio3 BioSciences
closes $30M IPO
02/27/13Celladon
Corporationcloses $50.6M IPO
05/15/2013Kite Phara raises $35M
in Series A round
07/01/2013Tengion, Inc. raises $18.6M
07/10/2013ViaCyte, Inc.
raises $10.6M in private equity
08/26/2013Argos
Therapeutics, Inc. raises $42.5M in a Series E round
08/13/2013Opexa Therapeutics, Inc.
raises $19.3M in public offering
09/04/2013 iPierian
secures $30M in venture financing
06/04/2013StemCells, Inc. secures $30M
07/30/2013Cellular Dynamics
International closes $46.1M IPO
09/23/2013Sangamo
BioSciences raises $74.2M in public offering
11/25/13Editas Medicine raises
$43M in a Series A round
10/04/13Fate Therapeutics closes $46M IPO
11/06/2013Lion Biotechnologies
raises $23.3M in private placement
03/19/2014Sangamo
BioSciences raises $100M in public offering
02/10/2014uniQure NV closes
$91.8M IPO
01/10/2014AGTC closed $50M IPO
12/12/13MiMedix raises $34M in public
offering
01/10/2014Athersys, Inc. raises
$20.5M in direct offering
11/25/2013Northwest Biotherapeutics, Inc.
raises $27M in public offering
02/20/2014Argos Therapeutics, Inc.
closes $45M IPO
01/04/14Bellicum
Pharmaceuticals, Inc. raises $14.7M in Series B Round
March2013
April2013
May2013
June2013
July2013
August2013
September2013
October2013
November2013
December2013
January2014
February2014
March2014
A Sampling of Noteworthy FinancingsMarch 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.”
23
01/13/13Juno Therapeutics, Inc. raises
$145M in a Series A round
02/12/13Voyager Therapeutics
raises $45M in Series A round
03/14/13Mesoblast Ltd. raises $175.3M
in private placement
05/28/2013Jennerex
Biotherapeutics, Inc. raises $21.6M in
private placement
06/24/2013bluebird bio closes
$116.1M IPO
08/12/2013Fate Therapeutics raises $20M in private offering
10/08/2013StemCells, Inc. raises $18.6M
in public offering
10/09/2013NeoStem raises
$40.3M in public offering
11/20/2013TiGenix NV raises
$16.2 million in private placement
10/22/13Spark Therapeutics launches with $50M capital commitment
12/13/2013Stem Cell
Therapeutics raises $31.13
in private placement
07/04/13Cardio3 BioSciences
closes $30M IPO
02/27/13Celladon
Corporationcloses $50.6M IPO
05/15/2013Kite Phara raises $35M
in Series A round
07/01/2013Tengion, Inc. raises $18.6M
07/10/2013ViaCyte, Inc.
raises $10.6M in private equity
08/26/2013Argos
Therapeutics, Inc. raises $42.5M in a Series E round
08/13/2013Opexa Therapeutics, Inc.
raises $19.3M in public offering
09/04/2013 iPierian
secures $30M in venture financing
06/04/2013StemCells, Inc. secures $30M
07/30/2013Cellular Dynamics
International closes $46.1M IPO
09/23/2013Sangamo
BioSciences raises $74.2M in public offering
11/25/13Editas Medicine raises
$43M in a Series A round
10/04/13Fate Therapeutics closes $46M IPO
11/06/2013Lion Biotechnologies
raises $23.3M in private placement
03/19/2014Sangamo
BioSciences raises $100M in public offering
02/10/2014uniQure NV closes
$91.8M IPO
01/10/2014AGTC closed $50M IPO
12/12/13MiMedix raises $34M in public
offering
01/10/2014Athersys, Inc. raises
$20.5M in direct offering
11/25/2013Northwest Biotherapeutics, Inc.
raises $27M in public offering
02/20/2014Argos Therapeutics, Inc.
closes $45M IPO
01/04/14Bellicum
Pharmaceuticals, Inc. raises $14.7M in Series B Round
March2013
April2013
May2013
June2013
July2013
August2013
September2013
October2013
November2013
December2013
January2014
February2014
March2014
24
The Alliance for Regenerative Medicine’s Science and Technology Committee began a project in the summer of 2013 to survey the R&D, 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 RespondentsAllergan, 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
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
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 R&D 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.
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%SomewhatImportant
6%Not at allImportant
6%N/A
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%
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 R&D 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
30
Where Pharma Sees Major Therapeutic Opportunities
Here and Now OpportunitiesThe 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 OpportunitiesIn 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 OpportunitiesNeurodegenerative 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.”
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
32
Where Pharma Sees Major Challenges
Lack of Predictable and Clear Regulatory GuidanceOf 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-UpThe 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.”
33
Uncertain Financing EnvironmentDespite 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 EnvironmentThroughout 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.”
34
Potency Assay ValidationThe 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 GoodsAfter 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.”
35
Product Consistency and StandardsResults 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 ExpertiseSixty-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 LogisticsSupply 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.”
36
MembershipRegenerative MedicineRegenerative MedicineALLIANCEfor
CompaniesAastrom 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
37
TissueGene, Inc.
Tissue Genesis, Inc.
TrakCel Ltd.
Vet-Stem, Inc.
ViaCyte, Inc.
InvestorsAsset Management Ventures
Kentucky Seed Capital Fund
Novitas Capital
Toucan Capital
Triathlon Medical Ventures
Patient Advocates/Foundations/AssociationsAssociation 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 InstitutionsCleveland 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
AffiliatesAlphaMed Press
European AffiliatesAndalusian 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
Regenerative MedicineRegenerative MedicineALLIANCEfor
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