Targeted Protein Degradation by Proteasomal, Lysosomal & Autophagy Pathways 2022: an industry landscape analysis of stakeholders, technologies, pipeline, partnering and financing
Targeted Protein Degradation by Proteasomal, Lysosomal & Autophagy Pathways 2022:
an industry landscape analysis of stakeholders, technologies, pipeline, partnering and financing
This report describes and analyzes the field of Targeted Protein Degradation (TPD) from an industry perspective as of March 2022.
The report provides essential information about and analysis of
- Pure-play TPD technology companies (molecular glues, heterobifunctional degraders, lysosomal and autophagic pathway degraders);
- Diversified technology companies with a TPD platform;
- Major pharma companies with a stake in TPD (in-house, partnering, licensing, acquisition);
- Proteasomal protein degrader technologies (heterobifunctional, molecular glue, monovalent degrader);
- Rational approaches for monofunctional molecular glue discovery at industry scale;
- Lysosomal and autophagy pathway degrader technologies (LYTACs, AUTOTACs, ATTECs etc);
- Clinical and preclinical experience with molecular glues and PROTACs;
- Profiles of TPD Drug Candidates;
- TPD Pipeline Analysis;
- Preferred Targets of TPDs;
- Preferred E3 ligases and their binders;
- Technologies for discovery of binders to proteins-of-interest and E3 ligases;
- Venture capital financing of TPD technology companies;
- Financing by IPO and follow-on public offerings;
- Revenues from TPD discovery and licensing deals.
Targeted protein degradation is a strongly and rapidly emerging new therapeutic modality based on the promise to overcome limitations of traditional small molecule drug modalities, such as limited access to difficult-to-drug targets and development of drug resistance. TPD technology is being adopted by most major pharmaceutical companies as it is regarded as a key technology platform. Pure-play TPD technology companies make progress by advancing their drug candidates into clinical studies. Many biotech companies are diversifying their platforms by adding TPD technology.
Investors welcome companies with TPD technologies as evidenced by the continuous flow of money to foster development of TPD technology and TPD drug candidates. Since April of 2020, five pure-play TPD technology companies went public and successfully raised a total of US$ 2.14 bln. The average market capitalization of five NASDAQ listed TPD technology companies was US$ 1.5 bln as of March 4, 2022. Series A-E financing rounds of 23 pure-play TPD technology companies brought in a total of US$ 1,778 mln of venture capital and equity investment. Partnering revenues are another important source of funding. As the TPD pipeline is maturing with favorable clinical outcomes, a recent licensing deal for a clinical phase II estrogen receptor PROTAC justified up-front payment and equity investment of US$ 1 bln.
This report describes and analyzes the industry landscape of targeted protein degradation by proteasomal-, lysosomal- and autophagy-targeted technologies. The report is based on information retrieved from 69 technology companies, 23 pharmaceutical companies and three academic institutions with publicly known industry ties.
The report includes Tables which summarize specific information to allow comprehensive comparisons. Illustrations are used to explain the mechanism of action of the various TPD technologies, pharmacologic effects and molecular structures.
Whenever possible, the profiles of TPD technology companies address the following aspects:
- General overview (founders, foundation year, technology source, location, number of employees), non-TPD technologies if applicable;
- Financial situation and funding history;
- Technology overview;
- Partnering;
- Pipeline.
Description of pharmaceutical companies generally is limited to activities with respect to TPD for publicly known in-house activities, for R&D collaboration and licensing and for acquisitions (Merck, Bayer, Amgen and Bristol Myers Squib).
The heterogenous profiles of the 69 technology companies demands assignation to “clusters” of companies with similar characteristics to allow a systematic comparison of 33 pure-play TPD technology companies focused on proteasomal pathway or non-proteasomal pathway technologies; 26 technologically diversified companies with TPD technologies; and the remainder of 10 companies.
Specific profiles are provided for 31 TPD technologies, separately for proteasomal molecular glue/monovalent degrader; proteasomal heterobifunctional degraders, lysosomal & autophagy pathway degraders and the remainder.
Specific profiles are provided for 48 TPD drug candidates, separately for the same four TPD modalities as for TPD technologies.
All information in the three chapters of Company Profiles, Technology Profiles and Drug Candidate Profiles are fully referenced with 117 scientific references, in most cases with hyperlinks with immediate online access to the source of information (abstracts, Poster, Presentations). Non-scientific references, such as press releases, annual reports or company presentations, are disclosed within the text with an embedded hyperlink leading to the source of information. Details about R&D strategy, collaboration and licensing agreements, acquisitions, financing rounds and sources are described in the company profiles.
What will you find in the report?
- Profiles of pure-play and diversified Targeted Protein Degrader (TPD technology companies;
- Description of Big Pharma’s role in the field (in-house R&D, partnering, acqusition and investing);
- Comprehensive description and analysis of emerging proteasomal and lysosomal/autophagic TPD technologies;
- TPD Technology selection and preferences of major pharma;
- Analysis of TPD technologies;
- Technologies for discovery of molecular glues, difficult to drug targets and E3 ligase binders;
- Pharmacologic profiles of Targeted Protein Degraders (TPD);
- Target selection, pipeline analysis and competition of drug candidates;
- Description and analysis of financing rounds (capital raised, investors);
- Economic terms of collaboration and licensing deals;
- Sources of financing.
Who will benefit from the report?
- Venture capital, private equity and investment managers;
- Managers of Big Pharma venture capital firms;
- Financial analysts;
- Business development and licensing (BDL) specialists;
- CEO, COO and managing directors;
- Corporate strategy analysts and managers;
- Chief Technology Officer;
- R&D Portfolio, Technology and Strategy Management;
- Clinical and preclinical development specialists.
Table of Contents
Abbreviations
1 Executive Summary
2 Introduction, Overview & Methodology
3 Analysis of TPD Stakeholders
3.1 Targeted Protein Degradation (TPD) Technology Companies
3.1.1 Overview
3.1.2 Pure-Play TPD Companies Focused on Molecular Glue & Monovalent Proteasomal Degraders
3.1.3 Pure-Play TPD Companies Focused on Heterobifunctional Proteasomal Degraders
3.1.4 Pure-Play TPD Companies Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders
3.1.5 Pure-Play TPD Companies Focused on Lysosomal & Autophagic (Non-Proteasomal) Degradation Technologies
3.1.6 Diversified Technology Companies with One Focus on Heterobifunctional Proteasomal Degraders
3.1.7 Diversified Technology Companies with Various TPD Technology Profiles
3.1.8 Remainder of Technology Companies with Various TPD Technology Profiles
3.2 Pharmaceutical Companies with TPD Interests
3.2.1 Overview of Major Pharma Companies as Stakeholders in TPD
3.2.2 Profile of Major Pharma’s Interest in Targeted Protein Degradation (TPD) R&D
3.2.3 Scope of Major Pharma‘s Partnering Activities in Targeted Protein Degradation (TPD)
4 Analysis of TPD Technologies
4.1 Analysis of Molecular Glue & Monovalent Proteasomal TPD Technologies
4.2 Analysis of Heterobifunctional Proteasomal TPD Technologies
4.3 Analysis of Lysosomal & Autophagy Pathway TPD Technologies
5 Analysis of TPD Pipeline, Targets and Product Candidates
5.1 Molecular Glue & Monovalent Proteasomal Targeted Protein Degraders
5.1.1 Clinical & Non-Clinical Development Pipeline of Molecular Glue Degraders: Targets and Experience
5.1.2 Preclinical R&D Pipeline & Targets of Molecular Glue & Monovalent Protein Degraders
5.2 Heterobifunctional Proteasomal Targeted Protein Degraders
5.2.1 Clinical & Non-Clinical Development Pipeline of Heterobifunctional Degraders
5.2.2 Preclinical R&D Pipeline of Heterobifunctional Degraders
5.2.3 Protein-of-Interest Targets and E3 Ligases Addressed by Heterobifunctional Proteasomal Degraders
5.2.4 E3 Ligases and Binders
5.3 Lysosomal & Autophagy Pathway Protein Degraders
5.4 Remainder of Targeted Protein Degraders
6 Business, Financing & Partnering
7 Profiles of Stakeholders in Targeted Protein Degradation (TPD)
7.1 Pure-Play TPD Companies Focused on Molecular Glue & Monovalent Proteasomal Degraders
7.1.1 Coho Therapeutics
7.1.2 Degron Therapeutics
7.1.3 Dunad Therapeutics
7.1.4 f5 Therapeutics
7.1.5 Monte Rosa Therapeutics
7.1.6 Neomorph
7.1.7 Plexium
7.1.8 Proxygen
7.1.9 Seed Therapeutics
7.1.10 Venquis Therapeutics
7.2 Pure-Play TPD Companies Focused on Heterobifunctional Proteasomal Degraders
7.2.1 Amphista Therapeutics
7.2.2 Arvinas
7.2.3 Cullgen
7.2.4 Dialectic Therapeutics
7.2.5 FIMECS
7.2.6 Orum Therapeutics
7.2.7 PolyProx Therapeutics
7.2.8 Ranok Therapeutics
7.2.9 Ubix Therapeutics
7.3 Pure-Play TPD Companies Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders
7.3.1 AnHorn Medicines
7.3.2 C4 Therapeutics
7.3.3 Captor Therapeutics
7.3.4 Celeris Therapeutics
7.3.5 Kymera Therapeutics
7.3.6 Pin Therapeutics
7.3.7 ProteoVant Therapeutics
7.3.8 Uppthera
7.4 Pure-Play TPD Companies Focused on Lysosomal & Autophagic (Non-Proteasomal) Degraders
7.4.1 Lycia Therapeutics
7.4.2 AUTOTAC Bio
7.4.3 Calporta Therapeutics (acquired by Merck)
7.4.4 Caraway Therapeutics
7.4.5 Casma Therapeutics
7.4.6 PAQ Therapeutics
7.5 Diversified Technology Companies with One Focus on Heterobifunctional Proteasomal Degraders
7.5.1 Accutar Biotechnology
7.5.2 Aurigene Discovery Technologies
7.5.3 BeiGene
7.5.4 Foghorn Therapeutics
7.5.5 Frontier Medicines
7.5.6 Haisco Pharmaceutical Group
7.5.7 Hinova Pharmaceuticals
7.5.8 Jing Medicine Technology
7.5.9 Kintor Pharmaceuticals
7.5.10 Nurix Therapeutics
7.5.11 Polymed Biopharma
7.5.12 Progenra
7.5.13 Ribon Therapeutics
7.5.14 Ryvu Therapeutics
7.5.15 VectorY
7.5.16 Voronoi (B2S Bio)
7.5.17 XPose Therapeutics
7.6 Diversified Technology Companies with Various TPD Technology Profiles
7.6.1 Orionis Therapeutics
7.6.2 Kangpu Biopharmaceutical Co.
7.6.3 BioTheryX
7.6.4 Biohaven
7.6.5 Vividion Therapeutics (acquired by Bayer)
7.6.6 Phoremost
7.6.7 Origami Therapeutics
7.6.8 Prazer Therapeutics
7.6.9 Prelude Therapeutics
7.7 Remainder of Techology Companies with Various TPD Technology Profiles
7.7.1 Ascentage Pharmaceuticals
7.7.2 Cullinan Oncology
7.7.3 Janpix – Centessa Pharmaceuticals
7.7.4 JW Pharmaceuticals
7.7.5 NeoImmuneTech
7.7.6 Salarius Pharmaceuticals
7.7.7 HB Therapeutics
7.7.8 Isoprene Pharmaceuticals
7.7.9 Ligature Therapeutics
7.7.10 Trilo Therapeutics
7.8 Pharmaceutical Companies with Stakes in Targeted Protein Degradation
7.8.1 AbbVie
7.8.2 Almirall
7.8.3 Amgen
7.8.4 Bayer
7.8.5 Biogen
7.8.6 Boehringer Ingelheim
7.8.7 Bristol Myers Squibb
7.8.8 Calico
7.8.9 Debiopharm
7.8.10 Eisai
7.8.11 Eli Lilly
7.8.12 Fosun Pharma
7.8.13 Gilead Sciences
7.8.14 GlaxoSmithKline
7.8.15 Janssen
7.8.16 Merck & Co
7.8.17 Merck KGaA
7.8.18 Novartis
7.8.19 Pfizer
7.8.20 Roche
7.8.21 Sanofi
7.8.22 SK Holdings
7.8.23 Vertex Pharmaceuticals
7.9 Academia with TPD Industry Partnerships
7.9.1 Center for Protein Degradation (CPD) at Dana-Farber Cancer Institute
7.9.2 Centre for Targeted Protein Degradation (CeTPD) at University of Dundee
7.9.3 Targeted Protein Degradation and Drug Discovery Laboratory at IRB Barcelona
8 Profiles of Targeted Protein Degradation (TPD) Technologies
8.1 Profiles of Molecular Glue & Monovalent TPD Technologies
8.1.1 Allo-Glue Platform – Orionis
8.1.2 DELPhe Technology Platform – Plexium
8.1.3 Monovalent TPD Technology – Dunad
8.1.4 NExMods Platform – f5 Therapeutics
8.1.5 Optigrade Technology Platform – Captor
8.1.6 Protein Homeostatic Modulators (PHM) – BioTheryX
8.1.7 QuEEN Platform – Monte Rosa
8.1.8 TORPEDO Platform – C4 Therapeutics
8.2 Profiles of Heterobifunctional Proteasomal TPD Technologies
8.2.1 ACCU-Degron Technology Platform – Accutar
8.2.2 AIMCADD Platform for Discovery of BIGPRO Protein Degraders – AnHorn
8.2.3 ALMOND Technology – Aurigene
8.2.4 Amphista Degrader Technology – Amphista
8.2.5 Antibody neoDegrader Conjugate (AnDC) Technology – Orum
8.2.6 CDAC Technology – BeiGene
8.2.7 Chaperone-Mediated Protein Degradation (CHAMP) Technology – Ranok
8.2.8 Degraducer Technology – Ubix
8.2.9 DELigase Technology Platform – Nurix
8.2.10 “Drug the Undruggable Targets” Discovery Platform – Frontier
8.2.11 Pegasus Drug Discovery Platform – Kymera
8.2.12 PROTAC Discovery Engine – Arvinas
8.2.13 RaPPIDS Technology Platform – FIMECS
8.2.14 SITESEEKER Target Discovery Platform – PhoreMost
8.2.15 uSMITE Technology – Cullgen
8.3 Profiles of Lysosomal & Autophagy Pathway TPD Technologies
8.3.1 ATTEC Technology – PAQ
8.3.2 Autophagy Degrader Platform (ADP) – Casma
8.3.3 AUTOTAC Technology – AUTOTAC
8.3.4 Lysosomal Drug Discovery Platform – Caraway
8.3.5 LYTAC Technology Platform – Lycia
8.3.6 Molecular Degrader of Extracellular Protein (MoDE) Platform – Biohaven
8.4 Other TPD-Related Technologies
8.4.1 Chemoproteomics Platform for Discovery of E3 Ligands – Vividion
8.4.2 ORICISION Technology Platform – Origami
9 Profiles of TPD Product Candidates
9.1 Molecular Glue & Monovalent Protein Degraders
9.1.1 AMG-193
9.1.2 BRD4 Monovalent Degrader
9.1.3 BTX-1188
9.1.4 CC-90009; Eragidomide
9.1.5 CC-91633; BMS-986397
9.1.6 CC-92480
9.1.7 CC-99282
9.1.8 CFT7455
9.1.9 Iberdomide (CC-220)
9.1.10 JPX-1188
9.1.11 KPG-121
9.1.12 KPG-818
9.1.13 MRT-2359
9.1.14 SP-3164
9.2 Heterobifunctional Proteasomal Targeted Protein Degraders
9.2.1 AC-176
9.2.2 AC0682
9.2.3 APG-265
9.2.4 ARD-1671
9.2.5 ARV-471
9.2.6 ARV-766
9.2.7 AU-19820
9.2.8 Bavdegalutamide; ARV-110
9.2.9 BCL6 PROTAC
9.2.10 BGB-16673
9.2.11 CC-94676
9.2.12 CFT1946
9.2.13 CFT8634
9.2.14 CFT8919
9.2.15 CT-03
9.2.16 DT2216
9.2.17 FHD-609
9.2.18 FIM-01
9.2.19 GT-19506
9.2.20 GT-20029
9.2.21 HP518
9.2.22 KT-253
9.2.23 KT-333
9.2.24 KT-413
9.2.25 KT-474; SAR444656
9.2.26 NX-2127
9.2.27 NX-5948
9.2.28 RBN012811
9.2.29 RNK05047
9.2.30 SD-436
9.2.31 UBX-303
9.3 Lysosomal & Autophagy Pathway Protein Degraders
9.3.1 TMEM175 Program
9.3.2 TRPML1 Modulators
9.4 Remainder of Targeted Protein Degraders – Not Defined
9.4.1 HB-007
9.4.2 Mnk1/2 Degraders
9.4.3 PRT-SCA2
10 References
ADDENDUM: Competitor Analysis
Add 1 Molecular Glue & Monovalent Small Molecule Proteasomal Targeted Protein Degradation
Add 2 Heterobifunctional Proteasomal Targeted Protein Degradation
Add 3 Lysosomal & Autophagy Pathway Targeted Protein Degradation
Add 4 Remainder of Targeted Protein Degradation
Figures & Tables
Table 1 Assignation to Clusters of Technology Companies Active in the TPD Field
Table 2 Overview of Pure-Play, Cluster 1 Companies – Focused on Molecular Glue & Monovalent Proteasomal Degraders
Table 3 Overview of Pure-Play, Cluster 2 Companies – Focused on Heterobifunctional Proteasomal Degraders
Table 4 Overview of Pure Play, Cluster 3 Companies – Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders
Table 5 Overview of Pure Play, Cluster 4 Companies – Focused on Lysosomal & Autophagy (Non-Proteasomal) Degraders
Table 6 Overview of Diversified Cluster 5 Companies – with One Focus on Heterobifunctional Proteasomal Degraders
Table 7 Overview of Diversified Cluster 6 Companies with Various TPD Technology Profiles
Table 8 Overview of Cluster 7 Companies with Various TPD Technology Profiles
Table 9 Overview of Major Pharma Stakes in TPD
Table 10 Profile of Major Pharma‘s Interests in Targeted Protein Degradation (TPD) R&D
Table 11 Scope of Major Pharma‘s Partnering Activities in Targeted Protein Degradation (TPD)
Table 12 Overview of Molecular Glue & Monovalent Proteasomal Protein Degrader Discovery Technologies
Table 13 Overview of Heterobifunctional Proteasomal Protein Degrader Discovery Technologies
Table 14 Overview of Lysosomal & Autophagic Pathway TPD Discovery Technologies
Table 15 Overview of Remainder of TPD Discovery Technologies
Table 16 Overview of Targeted Protein Degrader (TPD) Pipeline
Table 17 Pipeline of Clinical & Non-Clinical Development Stage Molecular Glue & Monovalent Protein Degraders
Table 18 Preclinical Pipeline and Targets of Molecular Glue & Monovalent Protein Degraders
Table 19 Pipeline of Clinical & Non-Clinical Development Stage Heterobifunctional Proteasomal Protein Degraders
Table 20 Preclinical Pipeline of Heterobifunctional Proteasomal Protein Degraders
Table 21 Overview of Proteins-of-Interest for Heterobifunctional Proteasomal Degraders
Table 22 Lysosomal Pathway Targeted Protein Degraders
Table 23 Autophagy Pathway Protein Degraders
Table 24 Remainder of Targeted Protein Degraders
Table 25 Sources of Financing for TPD Technology Companies
Table 26 Investors of TPD Technology Companies
Table 27 Partnering Terms of Agreements between TPD Technology Companies and Major Pharmaceutical Companies
Table 28 Molecular Glue Degrader Pipeline of Monte Rosa Therapeutics
Table 29 Discovery Pipeline of Plexium’s DELPhe-Derived Targeted Protein Degraders
Table 30 Overview of Arvinas’ Partnerships for Targeted Protein Degradation
Table 31 Arvinas’ PROTAC Degrader Pipeline
Table 32 C4 Therapeutics’ Proprietary MonoDAC & BiDAC Pipeline
Table 33 Targeted Protein Degrader Pipeline of Captor Therapeutics
Table 34 Kymera Therapeutics’ Pipeline of Targeted Protein Degraders
Table 35 Targeted Protein Degrader Pipeline of Proteoant Therapeutics
Table 36 AUTOTAC Discovery Programs of AUTOTAC Bio
Table 37 Accutar Biotechnology’s Pipeline of Small Molecule Chimeric Degraders
Table 38 Targeted Protein Degrader Pipeline of Aurigene Discovery Technologies
Table 39 Foghorn Therapeutics’ Targeted Protein Degrader Pipeline
Table 40 Nurix Therapeutics’ Pipeline of Protein Degradation Chimeric Targeting Molecules (CTMs)
Table 41 Kangpu Biopharmaceuticals’ Pipeline of Cereblon Modulators
Table 42 Discovery of SPiDEM Molecules for Targeted Protein Degradation by Prazer Therapeutics
Table 43 CELMoD R&D Pipeline of Bristol Myers Squibb