TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016: Convergence of technologies opens business opportunities beyond CD19 CARTs
TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016:
Convergence of technologies opens business opportunities beyond CD19 CARTs
The report TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016: Convergence of technologies opens business opportunities beyond CD19 CARTs“ describes and analyzes the status of the adoptive cell therapy industry as of August 2016. The report covers autologous and allogeneic engineered chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapy candidates as well as natural killer (NK) cell and CAR engineered NK cells in research and development by biopharmaceutical companies. Cytotoxic lymphocytes (CTLs), donor lymphocyte infusions (TILs) and tumor infiltrating lymphocytes (TILs) complement the spectrum of the report.
The report highlights and discusses
However, clinical experience with CD19 CAR T-cells and other CAR T-cells for hematologic and solid tumors has revealed quite a number of hurdles. Part of them have to be addressed by protocol issues, such as the pre-conditioning chemotherapy problem, or clinical combination studies with checkpoint inhibitors to modulate the tumor micro-environment. But technological solutions are far more required to improve safety and efficacy as well as convenience and manufacturing of CAR T-cell therapies. Another big issue is the lack of strictly tumor-specific targets.
Among the key technologies are gene editing and TCR target discovery. Companies with such capabilities will have a strong position in financing, partnering and corporate development. This report describes the key players in the field and companies with complementary technologies ideal for joint ventures, or better, mergers.
The analytical evaluation in this report is based on retrieval of information about and detailed description of the profiles of 67 companies and 67 cell therapy product candidates. Information was obtained from 193 scientific references (abstracts, full papers, reviews), press releases, financial information, annual reports, presentations and webcasts. All information sources are fully referenced, either as scientific references or by hyperlinks embedded on the source description for online access to the source.
Who will benefit from this report?
Convergence of technologies opens business opportunities beyond CD19 CARTs
The report TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016: Convergence of technologies opens business opportunities beyond CD19 CARTs“ describes and analyzes the status of the adoptive cell therapy industry as of August 2016. The report covers autologous and allogeneic engineered chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapy candidates as well as natural killer (NK) cell and CAR engineered NK cells in research and development by biopharmaceutical companies. Cytotoxic lymphocytes (CTLs), donor lymphocyte infusions (TILs) and tumor infiltrating lymphocytes (TILs) complement the spectrum of the report.
The report highlights and discusses
- Company financing;
- Business development & financing;
- Improvements of CAR T-cell therapy incl. gene editing and universal CARTs;
- Engineered TCR T-cells, including TCR target discovery;
- The current status of DLIs, CTLs and TILs;
- Manufacturing of T-cells for adoptive cell therapy;
- NK cells and CAR engineered NK cells;
- International perspective on TCR & CAR T-cell and NK cell therapy; and
- Key success factors & convergence of technologies.
However, clinical experience with CD19 CAR T-cells and other CAR T-cells for hematologic and solid tumors has revealed quite a number of hurdles. Part of them have to be addressed by protocol issues, such as the pre-conditioning chemotherapy problem, or clinical combination studies with checkpoint inhibitors to modulate the tumor micro-environment. But technological solutions are far more required to improve safety and efficacy as well as convenience and manufacturing of CAR T-cell therapies. Another big issue is the lack of strictly tumor-specific targets.
Among the key technologies are gene editing and TCR target discovery. Companies with such capabilities will have a strong position in financing, partnering and corporate development. This report describes the key players in the field and companies with complementary technologies ideal for joint ventures, or better, mergers.
The analytical evaluation in this report is based on retrieval of information about and detailed description of the profiles of 67 companies and 67 cell therapy product candidates. Information was obtained from 193 scientific references (abstracts, full papers, reviews), press releases, financial information, annual reports, presentations and webcasts. All information sources are fully referenced, either as scientific references or by hyperlinks embedded on the source description for online access to the source.
Who will benefit from this report?
- Technology Officers
- Corporate Development
- Strategic Planning
- Business Development & Licensing
- Corporate Finance
- Portfolio Management
- Investors & Analysts
- Clinical Development
- Research & Development
1 Executive Summary
2 INTRODUCTION
3 COMPANY FINANCING
3.1 Stock Market
3.2 Partnering Deals
3.3 Early Stage Financing (VC, PE & Other Seed Money)
3.4 Summary & Conclusions
4 BUSINESS DEVELOPMENT & LICENSING
4.1 „Public-Private Partnerships“ between Academia and Industry
4.2 Corporate Alliances & Out-Licensing to Major Pharma & Biotech
4.3 In-Licensing from Pharma & Biotech
4.4 Collaborations & Joint Ventures
4.5 Corporate & Asset Acquisitions
5 IMPROVEMENT OF CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY
5.1 Improvement of Safety
5.1.1 Role of pre-conditioning regimen
5.1.2 Suicide genes as safety switch
5.1.3 Elimination genes as safety switches
5.1.4 Activation genes as safety switches
5.1.5 Safety knock-out
5.1.6 Tumor-specific activation
5.1.7 Prodrug approach
5.1.8 Safer T-cell signaling & activation
5.1.9 Transient CAR expression
5.1.10 Target selectivity & intratumoral delivery
5.2 Gene Editing
5.3 Improvement of Efficacy
5.3.1 T-cell subsets
5.3.2 Genetic modification of T-cells
5.3.3 T-Cell activation & expansion
5.3.4 CAR design: antigen-binding domain
5.3.5 CAR design: linker/spacer and transmembrane domain
5.3.6 CAR design: intracellular signaling domains
5.3.7 CAR design: armored CARs against tumor microenvironment
5.3.8 Immune checkpoint inhibition
5.3.9 T-cell auto-antigen knock-out
5.3.10 Target heterogeneity & target loss
5.4 Universal CAR T-Cells
5.5 Allogeneic CAR T-cells
6 COMPETITIVE CAR T-CELL PIPELINE ANALYSIS
6.1 CD19 CAR T-Cells
6.2 CD19 CART Pivotal Studies
6.3 CD19 CART Developments by Chinese Companies
6.4 Further CAR T-Cells against Hematologic Malignancies
6.5 CAR T-Cells against Solid Tumors
6.6 CAR T-Cell Developments in China
6.7 Access to CAR Targets & CAR Target Discovery
7 ENGINEERED TCR T-CELLS
7.1 TCR T-Cell Pipeline
7.2 TCR Target Discovery
7.2.1 SPEAR T-Cell Technology
7.2.2 Naturally Selected TCRs (BioNTech)
7.2.3 XPRESIDENT
7.2.4 TCR-GENErator
7.2.5 Single-Cell Sequencing (Juno)
7.2.6 Natural, High Affinity TCRs (Bellicum)
7.2.7 Sleeping Beauty Electroporation of TCRs
7.2.8 Combinatorial T Cell Receptor Exchange (CTE)
7.2.9 Tumor-Specific TCR Library (Medigene)
7.2.10 Phagemers (Nextera)
7.2.11 ALPHA Phage Display (Eureka)
7.2.12 Epitarget (AIT)
8 DONOR LYMPHOCYTE INFUSIONS (DLI)
9 CYTOTOXIC T-LYMPHOCYTES (CTL)
10 TUMOR INFILTRATING LYMPHOCYTES (TIL)
11 MANUFACTURING OF T-CELLS FOR ADOPTIVE CELL THERAPY
11.1 In-House Manufacturing
11.2 Manufacturing Time
12 NATURAL KILLER (NK) CELLS
13 INTERNATIONAL PERSPECTIVE ON TCR & CAR T-CELL THERAPY
14 KEY SUCCESS FACTORS & CONVERGENCE OF TECHNOLOGIES
15 COMPANY PROFILES
15.1 Major pharma & biotech companies
15.1.1 Amgen
15.1.2 Celgene
15.1.3 Eli Lilly
15.1.4 GlaxoSmithKline
15.1.5 Janssen
15.1.6 Merck KGaA
15.1.6 Novartis
15.1.7 ONO Pharmaceutical Co
15.1.8 Pfizer
15.1.9 Servier
15.1.10 Shire (Baxalta)
15.2 USA & Canada: technology and development companies
15.2.1 Atara Biotherapeutics
15.2.2 Aurora Biopharma
15.2.3 Bellicum Pharmaceuticals
15.2.4 Bluebird bio
15.2.5 CytomX Therapeutics
15.2.6 Eureka Therapeutics
15.2.7 Formula Pharmaceuticals
15.2.8 iCell Gene Therapeutics
15.2.9 Intrexon
15.2.10 Juno Therapeutics
15.2.11 Kite Pharma
15.2.12 Lion Biotechnologies
15.2.13 MaxCyte
15.2.14 Mustang Bio
15.2.15 Nantkwest
15.2.16 Poseida Therapeutics
15.2.17 Precision BioSciences
15.2.18 Sorrento Therapeutics
15.2.19 TNK Therapeutics
15.2.20 Triumvira Immunologics
15.2.21 Unum Therapeutics
15.2.22 Vor Biopharma
15.2.23 ZIOPHARM Oncology
15.3 Europe: technology & development companies
United Kingdom:
15.3.1 Adaptimmune Therapeutics
15.3.2 Autolus
15.3.3 Catapult Therapy TCR
15.3.4 Cell Medica
15.3.5 Chimeric Therapeutics
15.3.6 Leucid Bio
15.3.7 Oxford BioMedica
15.3.8 The Cell & Gene Therapy Catapult
France, Belgium & Italy
15.3.9 Cellectis
15.3.10 Celyad
15.3.11 MolMed
15.3.12 Theravectys
Germany
15.3.13 BioNTech
15.3.14 CPT - Cellex Patient Treatment & GEMoaB Monoclonals
15.3.15 Immatics
15.3.16 Medigene
15.3.17 Miltenyi Biotec
The Netherlands, Norway & Finland
15.3.18 Gadeta
15.3.19 Nextera
15.3.20 TILT Biotherapeutics
15.4 Asia
Japan & Korea
15.4.1 Green Cross Lab Cell
15.4.2 Takara Bio
China
15.4.3 American Yuva Biomed
15.4.4 Beijing Doing Biomedical
15.4.5 CARsgen Therapeutics
15.4.6 Cellular Biomedicine Group
15.4.7 Immune Therapeutics
15.4.8 Innovative Cellular Therapeutics
15.4.9 JW Biotechnology
15.4.10 PersonGen BioTherapeutics
15.4.11 Shanghai GeneChem
15.4.12 Shenyang Sunshine Pharmaceutical
15.4.13 Sinobioway Cell Therapy
16 CELL THERAPY PROFILES
16.1 CD19-targeted CAR T-cell therapeutics:
16.1.1 4SCAR19
16.1.2 BPX-401
16.1.3 CBM-CD19.1
16.1.4 CD19 CAR T-Cells (1st generation ZIOPHARM)
16.1.5 CD19 CAR T-Cells (2nd generation ZIOPHARM)
16.1.6 CTL019
16.1.7 CTL119
16.1.8 Fully human anti-CD19 CAR T (NCI & Kite)
16.1.9 JCAR014
16.1.10 JCAR015
16.1.11 JCAR017
16.1.12 KTE-C19
16.1.13 UCART19
16.2 CD123-targeted CAR T-cell therapeutics:
16.2.1 CART123
16.2.2 MB-102
16.2.3 UCART123
16.3 BCMA-targeted CAR T-cell therapeutics:
16.3.1 bb2121
16.3.2 CART-BCMA
16.4 Fc-targeted CAR T-cell therapeutics:
16.4.1 ACTR087
16.4.2 ATTCK20
16.5 IL-13R?2-targeted CAR T-cell therapeutics:
16.5.1 Anti-IL-13R? IgCD28TCR
16.5.2 MB-101
16.6 Other solid tumor-targeted CAR T-cell therapeutics:
16.6.1 Anti-CEA IgCD28TCR
16.6.2 Anti-c-Kit IgCD28TCR
16.6.3 Anti-GD3 IgCD28TCR
16.6.4 Anti-PSMA IgCD28TCR
16.6.5 AU105
16.6.6 BPX-601
16.6.7 CART-EGFRVIII
16.6.8 CBM-EGFR.1
16.6.9 CSG-GPC3
16.6.10 JCAR020
16.6.11 JCAR023
16.6.12 JCAR024
16.6.13 OXB-302
16.7 Other hematologic malignancy-targeted CAR T-cell therapeutics:
16.7.1 CAR-CD44v6
16.7.2 CBM-CD20.1
16.7.3 CBM-CD30.1
16.7.4 CD33 CAR
16.7.5 JCAR018
16.7.6 NKR-2
16.7.7 UCART38
16.7.8 UCARTCS1
16.8 MAGE (A3 / A4 / A10)-targeted TCR T-cell therapeutics:
16.8.1 MAGE A3 TCR (NCI & Kite)
16.8.2 MAGE A10c796 TCR
16.8.3 TB-1201
16.9 Alpha-Fetoprotein-targeted TCR & TCR-like T-cell therapeutics
16.9.1 AFP-TCR
16.9.2 ET1402L1
16.10 NY-ESO-1-targeted TCR T-cell therapeutics
16.10.1 NY-ESOc259; GSK9377794
16.10.2 TB-1301
16.11 WT1-targeted TCR T-cell therapeutics
16.11.1 Autologous WT1 TCR
16.11.2 JTCR016
16.12 TCR T-cell therapeutics against other targets
16.12.1 BPX-701
16.12.2 TEG
16.13 Cytotoxic T Lymphocyte (CTL) therapeutics
16.16.1 CMD-003; baltaleucel-T
16.13.2 CMV-CTL
16.13.3 Cytovir
16.13.4 EBV-CTL
16.13.5 WT1-CTL
16.14 Donor Lymphocyte Infusion (DLI) therapeutics
16.14.1 BPX-501
16.14.2 Zalmoxis
16.15 Tumor Infiltrating Lymphocyte (TIL) therapeutics
16.15.1 LN-144
16.15.2 LN-145
16.16 Natural Killer (NK) cell therapeutics
16.16.1 aNK; Neukoplast; NK-92
16.16.2 haNK; CD16-Neukoplast
16.16.3 Her2.taNK
16.16.4 MG4101
17 REFERENCES
2 INTRODUCTION
3 COMPANY FINANCING
3.1 Stock Market
3.2 Partnering Deals
3.3 Early Stage Financing (VC, PE & Other Seed Money)
3.4 Summary & Conclusions
4 BUSINESS DEVELOPMENT & LICENSING
4.1 „Public-Private Partnerships“ between Academia and Industry
4.2 Corporate Alliances & Out-Licensing to Major Pharma & Biotech
4.3 In-Licensing from Pharma & Biotech
4.4 Collaborations & Joint Ventures
4.5 Corporate & Asset Acquisitions
5 IMPROVEMENT OF CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY
5.1 Improvement of Safety
5.1.1 Role of pre-conditioning regimen
5.1.2 Suicide genes as safety switch
5.1.3 Elimination genes as safety switches
5.1.4 Activation genes as safety switches
5.1.5 Safety knock-out
5.1.6 Tumor-specific activation
5.1.7 Prodrug approach
5.1.8 Safer T-cell signaling & activation
5.1.9 Transient CAR expression
5.1.10 Target selectivity & intratumoral delivery
5.2 Gene Editing
5.3 Improvement of Efficacy
5.3.1 T-cell subsets
5.3.2 Genetic modification of T-cells
5.3.3 T-Cell activation & expansion
5.3.4 CAR design: antigen-binding domain
5.3.5 CAR design: linker/spacer and transmembrane domain
5.3.6 CAR design: intracellular signaling domains
5.3.7 CAR design: armored CARs against tumor microenvironment
5.3.8 Immune checkpoint inhibition
5.3.9 T-cell auto-antigen knock-out
5.3.10 Target heterogeneity & target loss
5.4 Universal CAR T-Cells
5.5 Allogeneic CAR T-cells
6 COMPETITIVE CAR T-CELL PIPELINE ANALYSIS
6.1 CD19 CAR T-Cells
6.2 CD19 CART Pivotal Studies
6.3 CD19 CART Developments by Chinese Companies
6.4 Further CAR T-Cells against Hematologic Malignancies
6.5 CAR T-Cells against Solid Tumors
6.6 CAR T-Cell Developments in China
6.7 Access to CAR Targets & CAR Target Discovery
7 ENGINEERED TCR T-CELLS
7.1 TCR T-Cell Pipeline
7.2 TCR Target Discovery
7.2.1 SPEAR T-Cell Technology
7.2.2 Naturally Selected TCRs (BioNTech)
7.2.3 XPRESIDENT
7.2.4 TCR-GENErator
7.2.5 Single-Cell Sequencing (Juno)
7.2.6 Natural, High Affinity TCRs (Bellicum)
7.2.7 Sleeping Beauty Electroporation of TCRs
7.2.8 Combinatorial T Cell Receptor Exchange (CTE)
7.2.9 Tumor-Specific TCR Library (Medigene)
7.2.10 Phagemers (Nextera)
7.2.11 ALPHA Phage Display (Eureka)
7.2.12 Epitarget (AIT)
8 DONOR LYMPHOCYTE INFUSIONS (DLI)
9 CYTOTOXIC T-LYMPHOCYTES (CTL)
10 TUMOR INFILTRATING LYMPHOCYTES (TIL)
11 MANUFACTURING OF T-CELLS FOR ADOPTIVE CELL THERAPY
11.1 In-House Manufacturing
11.2 Manufacturing Time
12 NATURAL KILLER (NK) CELLS
13 INTERNATIONAL PERSPECTIVE ON TCR & CAR T-CELL THERAPY
14 KEY SUCCESS FACTORS & CONVERGENCE OF TECHNOLOGIES
15 COMPANY PROFILES
15.1 Major pharma & biotech companies
15.1.1 Amgen
15.1.2 Celgene
15.1.3 Eli Lilly
15.1.4 GlaxoSmithKline
15.1.5 Janssen
15.1.6 Merck KGaA
15.1.6 Novartis
15.1.7 ONO Pharmaceutical Co
15.1.8 Pfizer
15.1.9 Servier
15.1.10 Shire (Baxalta)
15.2 USA & Canada: technology and development companies
15.2.1 Atara Biotherapeutics
15.2.2 Aurora Biopharma
15.2.3 Bellicum Pharmaceuticals
15.2.4 Bluebird bio
15.2.5 CytomX Therapeutics
15.2.6 Eureka Therapeutics
15.2.7 Formula Pharmaceuticals
15.2.8 iCell Gene Therapeutics
15.2.9 Intrexon
15.2.10 Juno Therapeutics
15.2.11 Kite Pharma
15.2.12 Lion Biotechnologies
15.2.13 MaxCyte
15.2.14 Mustang Bio
15.2.15 Nantkwest
15.2.16 Poseida Therapeutics
15.2.17 Precision BioSciences
15.2.18 Sorrento Therapeutics
15.2.19 TNK Therapeutics
15.2.20 Triumvira Immunologics
15.2.21 Unum Therapeutics
15.2.22 Vor Biopharma
15.2.23 ZIOPHARM Oncology
15.3 Europe: technology & development companies
United Kingdom:
15.3.1 Adaptimmune Therapeutics
15.3.2 Autolus
15.3.3 Catapult Therapy TCR
15.3.4 Cell Medica
15.3.5 Chimeric Therapeutics
15.3.6 Leucid Bio
15.3.7 Oxford BioMedica
15.3.8 The Cell & Gene Therapy Catapult
France, Belgium & Italy
15.3.9 Cellectis
15.3.10 Celyad
15.3.11 MolMed
15.3.12 Theravectys
Germany
15.3.13 BioNTech
15.3.14 CPT - Cellex Patient Treatment & GEMoaB Monoclonals
15.3.15 Immatics
15.3.16 Medigene
15.3.17 Miltenyi Biotec
The Netherlands, Norway & Finland
15.3.18 Gadeta
15.3.19 Nextera
15.3.20 TILT Biotherapeutics
15.4 Asia
Japan & Korea
15.4.1 Green Cross Lab Cell
15.4.2 Takara Bio
China
15.4.3 American Yuva Biomed
15.4.4 Beijing Doing Biomedical
15.4.5 CARsgen Therapeutics
15.4.6 Cellular Biomedicine Group
15.4.7 Immune Therapeutics
15.4.8 Innovative Cellular Therapeutics
15.4.9 JW Biotechnology
15.4.10 PersonGen BioTherapeutics
15.4.11 Shanghai GeneChem
15.4.12 Shenyang Sunshine Pharmaceutical
15.4.13 Sinobioway Cell Therapy
16 CELL THERAPY PROFILES
16.1 CD19-targeted CAR T-cell therapeutics:
16.1.1 4SCAR19
16.1.2 BPX-401
16.1.3 CBM-CD19.1
16.1.4 CD19 CAR T-Cells (1st generation ZIOPHARM)
16.1.5 CD19 CAR T-Cells (2nd generation ZIOPHARM)
16.1.6 CTL019
16.1.7 CTL119
16.1.8 Fully human anti-CD19 CAR T (NCI & Kite)
16.1.9 JCAR014
16.1.10 JCAR015
16.1.11 JCAR017
16.1.12 KTE-C19
16.1.13 UCART19
16.2 CD123-targeted CAR T-cell therapeutics:
16.2.1 CART123
16.2.2 MB-102
16.2.3 UCART123
16.3 BCMA-targeted CAR T-cell therapeutics:
16.3.1 bb2121
16.3.2 CART-BCMA
16.4 Fc-targeted CAR T-cell therapeutics:
16.4.1 ACTR087
16.4.2 ATTCK20
16.5 IL-13R?2-targeted CAR T-cell therapeutics:
16.5.1 Anti-IL-13R? IgCD28TCR
16.5.2 MB-101
16.6 Other solid tumor-targeted CAR T-cell therapeutics:
16.6.1 Anti-CEA IgCD28TCR
16.6.2 Anti-c-Kit IgCD28TCR
16.6.3 Anti-GD3 IgCD28TCR
16.6.4 Anti-PSMA IgCD28TCR
16.6.5 AU105
16.6.6 BPX-601
16.6.7 CART-EGFRVIII
16.6.8 CBM-EGFR.1
16.6.9 CSG-GPC3
16.6.10 JCAR020
16.6.11 JCAR023
16.6.12 JCAR024
16.6.13 OXB-302
16.7 Other hematologic malignancy-targeted CAR T-cell therapeutics:
16.7.1 CAR-CD44v6
16.7.2 CBM-CD20.1
16.7.3 CBM-CD30.1
16.7.4 CD33 CAR
16.7.5 JCAR018
16.7.6 NKR-2
16.7.7 UCART38
16.7.8 UCARTCS1
16.8 MAGE (A3 / A4 / A10)-targeted TCR T-cell therapeutics:
16.8.1 MAGE A3 TCR (NCI & Kite)
16.8.2 MAGE A10c796 TCR
16.8.3 TB-1201
16.9 Alpha-Fetoprotein-targeted TCR & TCR-like T-cell therapeutics
16.9.1 AFP-TCR
16.9.2 ET1402L1
16.10 NY-ESO-1-targeted TCR T-cell therapeutics
16.10.1 NY-ESOc259; GSK9377794
16.10.2 TB-1301
16.11 WT1-targeted TCR T-cell therapeutics
16.11.1 Autologous WT1 TCR
16.11.2 JTCR016
16.12 TCR T-cell therapeutics against other targets
16.12.1 BPX-701
16.12.2 TEG
16.13 Cytotoxic T Lymphocyte (CTL) therapeutics
16.16.1 CMD-003; baltaleucel-T
16.13.2 CMV-CTL
16.13.3 Cytovir
16.13.4 EBV-CTL
16.13.5 WT1-CTL
16.14 Donor Lymphocyte Infusion (DLI) therapeutics
16.14.1 BPX-501
16.14.2 Zalmoxis
16.15 Tumor Infiltrating Lymphocyte (TIL) therapeutics
16.15.1 LN-144
16.15.2 LN-145
16.16 Natural Killer (NK) cell therapeutics
16.16.1 aNK; Neukoplast; NK-92
16.16.2 haNK; CD16-Neukoplast
16.16.3 Her2.taNK
16.16.4 MG4101
17 REFERENCES
