Antibody-Drug Conjugates 2011 - Real Breakthrough Still To Come. A Technology, Stakeholder and R&D Pipeline Analysis





  

This report “Antibody-Drug Conjugates 2011 – Real Breakthrough Still To Come: A Technology, Stakeholder and R&D Pipeline Analysis” published in September 2011 provides the most complete compilation of information about antibody-drug conjugate (ADC) companies, technologies and products in R&D. A comprehensive analysis of the state of the art and key trends guides the reader through this complex subject. Stakeholders in the field of antibody-drug conjugates are analysed and their contribution to the growth ADC technology and products is assessed. A critical appraisal of the clinical results of active and discontinued ADC projects and products is provided. ADC technologies and products are challenged for their commercial value and growth potential. 

Scope of the report
•Drugs and Linkers Used in Antibody-Drug Conjugates
•Antibodies Used in Antibody-Drug Conjugates
•Analysis of Stakeholders in Antibody-Drug Conjugates
•Clinical Value of Antibody-Drug Conjugates
•R&D Pipeline Analysis of Antibody-Drug Conjugates
•Commercial Values of Antibody-Drug Conjugates
•Company Profiles
•Executive ADC Profiles
The recent approval of Seattle Genetics’ antibody-drug conjugate Adcetris has raised great enthusiasm among stakeholders in this field. Accelerated approval was based on stunning tumor response rates in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Analysts expect strong sales of the expensive therapy. However, the FDA request post-approval studies showing that the high response rates translate into improved survival and that the clinical benefit seen in a small study population of 160 patients can be confirmed in a larger population. Although these data do not have to delivered before 2018, Genentech will be the next company after Wyeth (now Pfizer) to come up with survival data of its solid tumor ADC trastuzumab emtansine expected for 2012-2014. So far, only two controlled studies with ADC compounds have been published: one with Mylotarg failed to show a survival benefit, but t-DM1 pleased with an improved safety profile versus the combination of naked antibody with systemic chemotherapy
 

Results of early stage clinical trials of a number of ADC projects promise anti-tumor activity in hematologic malignancies as well as in solid tumors, but also dose-limiting toxicities which still narrow the therapeutic window for the currently used drugs and linkers. Nevertheless, about half of the currently clinical stage ADC projects entered clinical development within the last year indicating a high interest in the industry which also is reflected by the numerous licensing deals of the technology providers with pharmaceutical and biotech companies. The attrition rate of ADC development projects so far is well within the rate in oncology, or even better. However, ADC technologies still can be improved and candidates are emerging but need more time for validation and maturation. 

Features and Benefits
•Understand available drug-linker technologies
•Identify key trends of novel ADC concepts and drug-linker technologies
•Understand the complexity of the chemistry, manufacturing and control of ADC products and which approaches can taken to reduce it
•Perceive a realistic target profile of current ADC compounds and how it can be improved;
•Understand which tumor antigens are targeted by ADCs and their role
•See which companies can provide solutions
•Understand the commercial value of ADC technologies and ADC products
 

  

  

  

  

1. Abbreviations 6 

2. Overview 7 

3. Executive Summary 8 

4. Drugs and Linkers Used in Antibody-Drug Conjugates 9 

5. Antibodies Used in Antibody-Drug Conjugates 20 

6. Analysis of Stakeholders in Antibody-Drug Conjugates 24 

7. Clinical Value of Antibody-Drug Conjugates 30 

8. R&D Pipeline Analysis of Antibody-Drug Conjugates 35 

9. Commercial Values of Antibody-Drug Conjugates 38 

10. Company Profiles 40 

Abbott 40
Aeterna Zentaris 40
Allozyne 42
Alpha Cancer Technologies 43
Ambrx 43
Amgen 43
Amunix 45
Anaphore 46
Astellas Pharma (Agensys) 46
AstraZeneca (MedImmune) 49
Bayer Healthcare Pharmaceuticals 50
Biogen Idec 52
Biotest 53
Bristol-Myers Squibb (Medarex) 54
Celldex Therapeutics 57
Centrose 60
Daiichi Sankyo 61
Genmab 62
GlaxoSmithKline 62
ImmunoGen 63
Immunomedics 75
Merrimack Pharmaceuticals 79
Mersana Therapeutics 80
Millennium: The Takeda Oncology Company 82
Nerviano Medical Sciences 84
Novartis 84
Pfizer (Wyeth) 85
PharmaMar 91
Philogen 92
Progenics Pharmaceuticals 92
Roche (Genentech) 94
Sanofi 103
Seattle Genetics 107
Spirogen 116
Sutro Biopharma 117
Synthon (Syntarga) 118
Tactic Pharma (Attenuon) 119
Wilex (Heidelberg Pharma) 120
References 123
 

Tables 159 

Table 1 Characterization of Antibody-Drug Conjugates 159
Table 2 Drugs in Use for Antibody-Drug Conjugates 159
Table 3 Seattle Genetics ADC Technology Licensing Agreements 10
Table 4 Immunogen ADC Technology Licensing Agreement 162
Table 5 Antibody-Drug Conjugates in IND and Clinical Stages 164
Table 6 Linkers in Use for Clinical-Stage Antibody-Drug Conjugates 166
Table 7 Advantages and Disadvantages of Linkers and Cytotoxic Drugs 12
Table 8 Companies Active in R&D of New Cytotoxic Drugs for ADCs 14
Table 9 Companies Active in R&D of New Linkers for ADCs 15
Table 10 Immunogenicity of Antibody-Drug Conjugates 20
Table 11 Number of drug molecules per antibody 21
Table 12 Activities of Companies in the ADC Field 24
Table 13 Strengths & Weaknesses of Integrated ADC Technology & Product Companies 25
Table 14 Emerging ADC Technology Companies 27
Table 15 Immunoconjugate & Alternative ADC Companies 28
Table 16 Reasons for Discontinuation of Clinical Stage Antibody-Drug Conjugates 30
Table 21 Main Clinical Trials with T-DM1 in Metastatic Breast Cancer 171
Table 18 Clinical Results of phase I/II stage Antibody-Drug Conjugates 34
Table 19 Antibody-Drug Conjugates in Non-Clinical Development and Preclinical R&D 172
Table 20 Antibody-Drug Conjugates Discontinued in Clinical Stages 179
Table 21 Targets of Antibody-Drug Conjugates 36
Table 22 Immunoconjugates with Non-Antibody Targeting Moiety 181
 

Executive ADC Profiles 182 

AEZS-108 182
AGS-16M8F 185
ASG-5ME 186
ASG-22ME 188
BAY 79-4620 189
BAY 94-9343 191
BIIB015 192
BT-062 195
CR011-vcMMAE 199
CR014-vcMAE 202
hRS7-SN-38 203
IMGN388 205
IMGN529 207
IMGN853 210
IMGN901 212
Inotuzumab ozogamicin 219
Labetuzumab-SN-38 225
LIV-1 ADC 227
MDX-1203 228
MDX-1204 230
MEDI-547 231
Milatuzumab-doxorubicin 233
MM-302 236
PSMA-ADC 238
RG7596 241
SAR3419 244
SAR566658 247
SGN-19A 249
SGN-35 250
SGN-75 261
Trastuzumab-DM1 264
Related CompaniesAbbott
Aeterna Zentaris
Allozyne
Alpha Cancer Technologies
Ambrx
Amgen
Amunix
Anaphore
Astellas Pharma (Agensys)
AstraZeneca (MedImmune)
Bayer Healthcare Pharmaceuticals
Biogen Idec
Biotest
Bristol-Myers Squibb (Medarex)
Celldex Therapeutics
Centrose
Daiichi Sankyo
Genmab
GlaxoSmithKline
ImmunoGen
Immunomedics
Merrimack Pharmaceuticals
Mersana Therapeutics
Millennium: The Takeda Oncology Company
Nerviano Medical Sciences
Novartis
Pfizer (Wyeth)
PharmaMar
Philogen
Progenics Pharmaceuticals
Roche (Genentech)
Sanofi
Seattle Genetics
Spirogen
Sutro Biopharma
Synthon (Syntarga)
Tactic Pharma (Attenuon)
Wilex (Heidelberg Pharma)