Intracellular Targets Made Druggable by TCR-like Antibodies, TCR Fusion Proteins & Cell-Penetrating Biologics 2018: An Industry Analysis of Technologies, Stakeholders, Deals & Trends

It is estimated that there are 3-4 times more intracellular targets than surface protein targets. However, these intracellular cancer targets are not accessible to traditional monoclonal antibody (mAb) therapies. Since many of these targets are not enzymes or surface receptors with readily druggable pockets, these important oncogenic proteins cannot be easily inhibited with small molecules. Thus, intracellular cancer-specific proteins, such as mutated oncogene products, transcription factors, protein adapters, and other nontraditional targets, remain inaccessible to current technologies used for FDA-approved drugs.

Therefore, novel technologies are needed to address historically undruggable targets and complex mechanisms, such as intracellular protein-protein interactions like p53 or Ras, ß-catenin and Myc.

Presentation of Target

On cell surface as peptide-MHC class I complex

Intracellular;
Intranuclear
Protein-protein interaction (PPI)

Target Examples

Neoantigens
Gp100; NY-ESO-1; MAGE-A, PRAME; WT1; MART-1

Beta-catenin; Myc; Ras

Therapeutic Modality

TCR fusion protein
TCR-like antibody

Cell penetrating peptide, miniprotein or antibody incl. shuttle

Effector Function

Fc-enhanced
Bispecific (T-cell recruiting)
Drug Conjugate

Inhibition

This report `Intracellular Targets made druggable by TCR-like Antibodies, TCR Fusion Proteins & Cell-Penetrating Biologics 2018: an industry analysis of technologies, stakeholders, deals & trends` brings you up-to-date regarding key technologies:

For identification and validation of intracellular targets,
For generation of T-cell receptors (TCR) and TCR fusion proteins,
For discovery of TCR-like antibodies, and
For construction of cell-penetrating peptides, proteins and antibodies.

The report furthermore describes the profiles of leading product candidates created by these technologies. The technology companies are presented and analyzed. Deals between Big Pharma and technology companies as well as collaboration and licensing deals between technology companies are highlighted. The value of technologies and product candidates are discussed regarding company acquisition prices, economic deal terms and financing rounds.

What will you find in the report?

Description and comparison of technologies for:

Discovery and validation of intracellular targets;
Discovery and optimization of T-Cell Receptors (TCRs);
Generation of TCR-like or TCR-mimic antibodies;
Generation of TCR fusion proteins
Generation of cell-penetrating peptides, proteins and antibodies.

Presentation and discussion of profiles of selected product candidates:

TCRL antibodies and TCR fusion proteins; and
Cell-penetrating peptides, miniproteins and single domain and Ig antibodies

Stakeholder analysis based on profiles of 45 companies active in the field
Analysis of partnering deals and financing rounds

1 Executive Summary2 Introduction & Overview3 Background

4 Technology Profiles

4.1 Overview & Discussion
4.1.1 Intracellular Target Discovery
4.1.2 TCR Discovery Technologies
4.1.3 Generation of TCR-like Antibodies
4.1.4 Generation of TCR Fusion Proteins against Intracellular Targets
4.1.5 Generation of Cell Penetrating Biologics against Intracellular Targets
4.2 Technologies for Discovery of Intracellular Targets
4.2.1 XPRESIDENT
4.2.2 Targets for TCRs (Immunocore)
4.2.3 Phosphopeptide Library
4.2.4 HTS Platform for Neoantigen Identification
4.2.5 ECLIPSE Platform
4.2.6 EpiTarget Platform
4.2.7 Soluble HLA (sHLA) Molecules
4.2.8 Phagemers & SSIp display
4.2.9 Peptide/MHC Complexes
4.2.10 TCR Target Discovery
4.3 Technologies for Discovery of TCRs
4.3.1 Naturally Selected TCRs
4.3.2 TCRs by ImmTAC Technology
4.3.3 HTS for TUMAP-Restricted TCRs
4.3.4 Natural TCR Library
4.3.5 Sleeping-Beauty Expression System
4.3.6 TCR-GENerator
4.3.7 T-Rx Mammalian TCR Display
4.3.8 Single Cell Sequencing Platform
4.3.9 Immune Repertoire Capture
4.3.10 Combinatorial TCR Exchange (CTE)
4.3.11 VelociT for T-Cell Receptor Discovery
4.4 Technologies for Generation of TCRL Antibodies
4.4.1 TandAb
4.4.2 BiTE
4.4.3 E-Alpha Phage Display
4.4.4 HuTARG Protein Engineering
4.4.5 MAR & TriTE
4.4.6 TCRL Antibodies
4.4.7 TCRm Antibodies
4.4.8 Ylanthia Fab library
4.4.9 TCRL ADCs
4.5 Technologies for Generation of TCR Fusion Proteins
4.5.1 ImmTAC
4.5.2 TCR Bispecifics
4.5.3 STAR
4.6 Technologies for Generation of Cell Penetrating Biologics
4.6.1 Cell-Penetrating alpha Bodies
4.6.2 Anti-DNA Autoantibodies
4.6.3 Cell Penetrating Mini Proteins (CPMP)
4.6.4 Feldan Shuttle
4.6.5 Shark VNARs
4.6.6 iMab
4.6.7 iTABs
4.6.8 Stapled Peptides
4.6.9 Single Domain Antibodies

5 Pipeline Analysis and Product Profiles

5.1 Overview Product Profiles and Pipeline Discussion
5.2 Profiles of Selected TCRL Antibodies & TCR Fusion Proteins
5.2.1 IMCgp100
5.2.2 ALT-801
5.2.3 H8F4
5.2.4 MMP1-003 TandAb
5.2.5 ESK1 & ESKM
5.2.6 RL1B
5.3 Profiles of Selected Cell Penetrating Peptides, Proteins & Antibodies
5.3.1 ALRN-6924
5.3.2 Anti-Mcl-1 CPAB
5.3.3 PAT-DX1 & Other Deoxymabs
5.3.4 RT11-i
5.3.5 SBT-100

6 Stakeholder Analysis & Company Profiles

6.1 Stakeholder Analysis and Overview of Company Profiles
6.2 Profiles of Companies with Target Discovery and TCR Fusion Protein Technologies
6.2.1 Agenus
6.2.2 Atreca
6.2.3 Immatics Biotechnologies
6.2.4 Immunocore
6.2.5 Regeneron Pharmaceuticals
6.3 Profiles of Companies with Target Discovery and TCR-Like Antibody Technologies
6.3.1 AbeXXa
6.3.2 Adicet Bio
6.3.3 MD Anderson Cancer Center
6.3.4 Pure MHC
6.4 Profiles of Companies with TCR Fusion Protein and/or TCRL Antibody Technologies
6.4.1 Affimed Therapeutics
6.4.2 NantCell (Altor Bioscience)
6.4.3 Eureka Therapeutics
6.4.4 Innovative Targeting Solutions (ITS)
6.4.5 Morphosys
6.4.6 Receptor Logic (now Pure MHC)
6.4.7 Timmune Biotech
6.5 Profiles of Companies with TCR Discovery Technologies only used for T-Cell Therapy
6.5.1 BioNTech
6.5.2 Gadeta
6.5.3 Gilead Sciences (Kite Pharma)
6.5.4 Juno Therapeutics
6.5.5 Medigene
6.5.6 ZIOPHARM Oncology
6.6 Profiles of Companies with Cell Penetrating (CP) Peptide, Protein or Antibody Technologies
6.6.1 Aileron Therapeutics
6.6.2 Complix
6.6.3 Elasmogen
6.6.4 Feldan Therapeutics
6.6.5 Fog Pharmaceuticals
6.6.6 Orum Pharmaceuticals
6.6.7 Patrys
6.6.8 Singh Biotechnology
6.6.9 Sorrento Therapeutics & LA Cell
6.7 Profiles of Big Pharma & Biotech Companies Active in the Intracellular Target and TCR & Cell Penetrating Biologics Field
6.7.1 AbbVie
6.7.2 Amgen
6.7.3 Astellas Pharma
6.7.4 AstraZeneca
6.7.5 Boehringer Ingelheim
6.7.6 Eli Lilly
6.7.7 GlaxoSmith-Kline
6.7.8 Janssen Biotech
6.7.9 Merck
6.7.10 Novartis
6.7.11 Roche
6.8 Profiles of Other Companies with Stakes in the Field of Intracellular Targets and TCR & Cell Penetrating Biologics
6.8.1 Nextera
6.8.2 Xencor
6.8.3 Zymeworks

7 Deals & Financing

7.1 Partnering Deals between Big Pharma and Technology Companies
7.2 Acquisitions of Technology Companies
7.3 Collaboration and Licensing Deals between Technology Companies
7.4 Financing Sources of Technology Companies

8 Trends & Outlook9 References