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

Table of Contents

            Abbreviations

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-13Rα2-targeted CAR T-cell therapeutics:
16.5.1  Anti-IL-13Rα IgCD28TCR
16.5.2  MB-101

16.6     Other solid tumor-targeted CAR T-cell therap

TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016:
Convergence of technologies opens business opportunities beyond CD19 CARTs

Tables in the Text:

Table 1 Company Financing by Public Offerings
Table 2 Company Financing by Partnering Deals
Table 3 Company Financing by Venture Capital, Private Equity & Other Seed Money
Table 4 Investors in Early Stage T-Cell & NK Cell Technology Companies
Table 5 Total Amount of Money Globally Raised in 2015/16
Table 6 Total Amount of Money Raised in 2015/16 in Europe ONLY
Table 7 North America: Partnering with & In-Licensing from Academia
Table 8 Europe: Partnering with & In-Licensing from Academia
Table 9 Asia: Partnering with & In-Licensing from Academia
Table 10 Corporate Alliances & Out-Licensing to Major Pharma & Biotech
Table 11 In-Licensing from Pharma & Biotech
Table 12 Collaborations & Joint Ventures
Table 13 Corporate & Asset Acquisitions
Table 14 Gene Editing Technologies for Engineering of T-Cells
Table 15 Overview of Corporate Allogeneic CAR T-cell Developments
Table 16 Molecular & Cellular Characteristics of anti-CD19 CAR T-Cell Therapies under Corporate Development outside of China
Table 17 Competing anti-CD19 CARTs in Pivotal Studies
Table 18 Molecular & Cellular Characteristics of anti-CD19 CAR T-Cell Therapies under Corporate Development outside of China
Table 19 Molecular & Cellular Characteristics of Further CAR T-Cell Therapies against Hematologic Malignancies under Corporate Development outside of China
Table 20 Molecular & Cellular Characteristics of CAR T-Cell Therapies against Solid Tumors under Corporate Development outside of China
Table 21 Molecular & Cellular Characteristics of Further CAR T-Cell Therapies against Hematologic Malignancies under Corporate Development in China
Table 22 Molecular & Cellular Characteristics of CAR T-Cell Therapies against Solid Tumors under Corporate Development in China
Table 23 Pipeline of TCR T-Cell Therapy Candidates in Development with Company Participation
Table 24 Technologies for TCR Target Discovery and TCR T-Cell Generation
Table 25 Contract Manufacturing Organizations for T-cells
Table 26 Manufacturing Time of Selected TCR & CAR T-Cells and CTLs
Table 27 Bellicum’s Switch and Costimulation Technologies
Table 28 Composition of Bellicum’s T-Cell Product Candidates
Table 29 Bellicum’s Pipeline of T-Cell Product Candidates
Table 30 Overview of Kite Pharma’s Access to Technologies
Table 31 Overview of the Characteristics of Juno’s CD19-Targeted CAR T-Cell Product Candidates
Table 32 Juno’s Development Program of CD19 CAR-Ts
Table 33: Overview of the Characteristics of Juno’s Further TCR & CAR T-Cell Product Candidates
Table 34 Juno’s Clinical Development Program of Further TCR & CAR T-Cell Product Candidates
Table 35 Overview of Kite Pharma’s Access to Technologies
Table 36 NCI-Initiated Clinical Studies of CAR & TCR T-Cell Product Candidates
Table 37 Overview of ZIOPHARM’s R&D Pipeline
Table 38 Molecular & Cellular Characteristics of Cellectis‘ Allogeneic CAR T-Cells
Table 39 Early Clinical Trials with Autologous CAR T Cells from CBMG
Table 40: Early Clinical Trials of Sinobioway’s CAR T-Cells
Table 41 Clinical Trials with CTL019
Table 42 Clinical Development Program of KTE-C19 CAR
Table 43 Early Clinical Trials with Adaptimmune’s NY-ESOc259T

TCR & CAR Engineered T-Cell and NK Cell Therapeutics 2016:
Convergence of technologies opens business opportunities beyond CD19 CARTs

Companies mentioned in the report

Adaptimmune
Adicet Bio
American Yuva Biomed
Amgen
Astellas Pharma
Atara Biotherapeutics
Aurora Biopharma
Autolus
Beijing Doing Biomedical
Bellicum Pharmaceuticals
BioNTech
BioVec
Bluebird bio
CARSgen Therapeutics
Catapult Therapy TCR
Celgene
Cell Medica
Cellectis
CellforCURE
Cellular Biomedicine Group
Cellular Therapeutics
Celyad
Chimeric Therapeutics
CPT – Cell Processing Therapy & GEMoab Monoclonals
CytomX Therapeutics
Eli Lilly
EUFETS
Eureka Therapeutics
Five Prime
Formula Pharmaceuticals
Gadeta
GlaxoSmithKline
Green Cross LabCell
iCell Gene Therapeutics
Immatics US
Immune Therapeutics
Innovative Cellular Therapeutics
Intrexon
Janssen
Juno Therapeutics
JW Biotechnology
Kite Pharma
Leucid Bio
Lion Biotechnologies
Lonza Wakersville
MaSTherCell
MaxCyte
Medigene
Merck KGaA
Miltenyi Biotec
MolMed
Mustang Bio
Nantkwest
Nextera
Novartis
ONO Pharmaceutical Co
Oxford BioMedica
Persongen Biomedicine
Pfizer
Poseida Therapeutics
Precision BioSciences
Progenitor Cell Therapy (PCT)
Regeneron Pharmaceuticals
Seattle Genetics
Servier
Shanghai GeneChem
Shenyang Sunshine Pharmaceutical
Shire (Baxalta)
Sinbioway Cell Therapy
Sorrento Therapeutics
Takara Bio
The Cell and Gene Therapy Catapult
Theravectys
ThermoFisher
TILT Biotherapeutics
TNK Therapeutics
Triumvira Immunologics
Universal Cells
Unum Therapeutics
ViroMed
Vor Biopharma
WuXi AppTec
ZIOPHARM Oncology