Claudin 18.2-Targeted Immunotherapy: a landscape analysis of stakeholders, drug modalities, pipeline and business opportunities from an industry perspective
Claudin 18.2-Targeted Immunotherapy: a landscape analysis of stakeholders, drug modalities, pipeline and business opportunities from an industry perspective
This report provides you with a landscape description and analysis of discovery and development of claudin 18.2 (CLDN18.2)-targeted antibody and cell therapy candidates from an industry perspective as of August 2023. CLDN18.2 is transmembrane protein selectively expressed on the cancer cell surface of gastric epithelial cells.
The report brings you up-to-date with information about and analysis of
- Claudin 18.2 target identification and validation;
- Differential expression profile of claudin 18.2 in health and tumor tissues;
- Incidence of cancers with significant expression of claudin 18.2 in major countries;
- Scope and economic terms of licensing agreements for anti-CLDN18.2 immunotherapy candidates and discovery technologies;
- Stakeholders in the field: major pharma and biotech, ex-China biotech companies; Chinese major pharma and Chinese emerging biopharma companies;
- Specific company profiles, especially of Chinese, including financial situation;
- Pipeline description and analysis regarding drug modalities, indications, territories (global vs regional), R&D stage;
- Preclinical and clinical experience with CLDN18.2 immunotherapy candidates;
- Specific profiles of anti-CLDN18.2 immunotherapy candidates.
The naked monoclonal antibody zolbetuximab has become the current gold standard and benchmark for all follow-on anti-CLDN18.2 immunotherapy candidates as zolbetuximab is the only candidate that has been evaluated in controlled pivotal clinical studies. Regulatory agencies in the US, the European Union, Japan and China have accepted license applications for zolbetuximab in June/July 2023 and potential approvals and market launches are expected during the course of 2024.
The clinical profile of zolbetuximab showed statistically significant and clinically relevant improvements in progression free survival by 1.94 or 1.41 months and in overall survival of 2.69 or 2.23 in the SPOTLIGHT or GLOW phase III trials, respectively. Major adverse events were gastrointestinal symptoms nausea, vomiting and decreased appetite. Furthermore, only 39.1% of gastric cancer patients were eligible to treatment with zolbetuximab. One of the inclusion criteria was expression of CLDN18.2 in tumor tissue defined by moderate to strong staining in ≥75% of cancer cells.
This product profile leaves sufficient space for improvements in efficacy, safety and patient eligibility by next generation anti-CLDN18.2 immunotherapy candidates. To generate more effective and safe CLDN18.2-targeted antibody and cell therapy candidates, several drug modalities with potential for enhanced effector function, increased safety and broader patient population have applied:
- Naked monoclonal antibodies (mAbs) with enhanced target affinity and increased ADCC, CDC & ADCP;
- Antibody-drug conjugates (ADCs) with improved linker & conjugation technology and payloads;
- Chimeric antigen receptor (CAR) T-Cells (CAR-T) with improved constructs (signalling domains, armored, modular design);
- Anti-CLDN18.2 Bispecific T-Cell Engaging (BiTE or TCE) Antibodies for recruitment of cytotoxic T-cells;
- 2-Targeted Bispecific Immuno-Oncology (I-O) Antibodies for checkpoint blockade or immune stimulation.
This report evaluates the industry landscape of claudin18.2-targeted novel antibody and cell therapy candidates. The report is based on the identification and description of 48 companies with research and development activities in the field and 68 distinct product candidates.
For each company, a profile has been elaborated providing information about the company background/history, the financial situation, relevant technology, partnering deals and CLDN18.2-specific pipeline overview.
Specific profiles of 56 anti-CLDN18.2 immunotherapy candidates have been prepared to describe design and construct of the candidate, applied technologies, the preclinical in vitro and in vivo profile and clinical experience, if available. All information is fully referenced, either with 107 scientific references (conference abstracts, Posters, presentations, full paper) or hyperlinks leading to the source of corporate information, such as press releases, corporate presentations, annual reports, SEC disclosures and homepage content.
What will you find in the report?
- Profiles of R&D companies active in the field;
- Description of Big Pharma’s role in the field (in-house R&D, partnering and investing);
- Comprehensive description and analysis of established and emerging drug modality technologies;
- Competitor and pipeline analysis for each drug modality applied in anti-CLDN18 immunotherapy candidates;
- Territories of major competition;
- Preclinical and clinical profiles of anti-CLDN18.2 immunotherapy candidates;
- Drug modality preferences of major pharma;
- Scope and economic terms of collaboration and licensing deals.
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;
- Patent attorneys and specialists;
- CEO, COO and managing directors;
- Corporate strategy analysts and managers;
- Chief Technology & Scientific Officer;
- R&D portfolio, technology and strategy managers;
- Clinical and preclinical development specialists
Table of Contents
Frequent Abbreviations
1 Executive Summary
2 Overview and Methodology
3 Discovery, Structure and Function of Claudin 18.2
3.1 Discovery of Claudin 18.2 as a highly lineage-specific cancer target
3.2 Structure and Function of Claudin 18.2
4 Expression Profile of Claudin 18.2 in Cancer
4.1 CLDN18.2 expression in gastric and gastro-esophageal junction (GEJ) cancer
4.2 CLDN18.2 expression in gastric, GEJ, pancreatic and other cancers
4.3 Summary of CLDN18.2 Expression in Cancer
5 Incidence of gastric, esophageal and pancreatic cancer
5.1 Gastric cancer
5.2 Esophageal cancer
5.3 Pancreatic cancer
6 CLDN18.2 Licensing Agreements
7 Analysis of Claudin 18.2 Stakeholders
7.1 Major Biopharmaceutical Companies outside of China with CLDN18.2 Programs
7.2 Other Biopharmaceutical Companies outside of China with CLDN18.2 Programs
7.3 Chinese Biopharmaceutical Companies with Clinical Development of CLDN18.2 Programs outside of China
7.4 Chinese Biopharmaceutical Companies with Clinical Development of CLDN18.2 Programs inside of China
7.5 Chinese Biopharmaceutical Companies with Non-Clinical & Preclinical R&D of CLDN18.2 Programs
8 Pipeline Analysis of CLDN18.2-Targeted Immunotherapy Candidates
8.1 CLDN18.2 Drug Modalities and Development Stage
8.2 Discontinued CLDN18.2 R&D Programs
8.3 Zolbetuximab as Benchmark for CLDN18.2-Targeted Immunotherapies
8.4 CLDN18.2-Targeted Naked Monoclonal Antibodies
8.4.1 Clinical Experience with Anti-CLDN18.2 Naked Monoclonal Antibodies
8.5 CLDN18.2 Targeted Antibody-Drug Conjugates (ADCs)
8.5.1 Clinical Experience with Anti-CLDN18.2 Antibody-Drug Conjugates
8.6 CLDN18.2 Targeted Chimeric Antigen Receptor T-cells (CAR-T)
8.6.1 Clinical Experience with Anti-CLDN18.2 CAR T-Cells
8.7 CLDN18.2 Targeted Bispecific T-Cell Engaging Antibodies
8.8 CLDN18.2 Targeted Bispecific Immuno-Oncology (I-O) Antibodies
8.8.1 CLDN18.2 x 4-1BB Bispecific Antibodies
8.8.2 CLDN18.2 x CD47 / SIRPα Bispecific Antibodies
8.8.3 CLDN18.2 x PD-L1 Bispecific Antibodies
8.8.4 CLDN18.2 x CD8 Bispecific Antibodies
9 Company Profiles
9.1 Major Biopharmaceutical Companies outside of China
9.1.1 Astellas Pharma
9.1.2 AstraZeneca
9.1.3 BioNTech
9.1.4 Bristol Myers Squibb
9.1.5 Merck
9.1.6 Roche
9.2 Other Biopharmaceutical Companies outside of China
9.2.1 ABL Bio
9.2.2 Abpro
9.2.3 CARTEXEL
9.2.4 Elevation Oncology
9.2.5 Integral Molecular
9.2.6 Leap Therapeutics
9.2.7 Phanes Therapeutics
9.2.8 SOTIO Biotech
9.2.9 TORL BioTherapeutics
9.2.10 Triumvira Immunologcics
9.3 Chinese Biopharmaceutical Companies with Clinical Development outside of China
9.3.1 Antengene
9.3.2 CARsgen Therapeutics
9.3.3 I-Mab Biopharma
9.3.4 Innovent Biologics
9.3.5 Jiangsu Hengrui Pharmaceuticals
9.3.6 La Nova Medicines
9.3.7 RemeGen
9.3.8 SparX Group
9.3.9 Transcenta Holding
9.3.10 Zai Lab
9.4 Chinese Biopharmaceutical Companies with Clinical Development inside China
9.4.1 Beijing Mabworks Biotech
9.4.2 Biotheus
9.4.3 CSPC Pharmaceutical Group
9.4.4 Gracell Biotechnologies
9.4.5 Jiangsu Aosaikang Pharmaceutical
9.4.6 L&L Biopharma
9.4.7 Legend Biotech
9.4.8 Nanjing Kaedi Biotherapeutics
9.4.9 Qilu Pharmaceutical
9.4.10 QureBio
9.4.11 Shandong Boan Biotechnology
9.4.12 Shanghai Junshi Biosciences
9.4.13 Shanghai Longyao Biotechnology
9.4.14 Sichuan Kelun-Biotech Biopharmaceutical
9.4.15 Suzhou Immunofoco Biotechnology
9.4.16 Zhejiang Doer Biologics
9.5 Chinese Biopharmaceutical Companies with Non-Clinical and Preclinical R&D
9.5.1 Akeso
9.5.2 Dragon Boat Biopharmaceutical
9.5.3 Elpiscience Biopharmaceutical
9.5.4 Genor Biopharma
9.5.5 OriCell Therapeutics
9.5.6 Shanghai Genbase Biotechnology
10 Anti-CLDN18.2 Drug Candidate Profiles
10.1 Naked Monoclonal Antibodies
10.1.1 AB011
10.1.2 ASKB589
10.1.3 BA1105
10.1.4 BC008
10.1.5 BNT141
10.1.6 DR30303
10.1.7 GB7004
10.1.8 IBI360
10.1.9 JS012
10.1.10 LM-102
10.1.11 MIL93
10.1.12 NBL-015; FL-301
10.1.13 Osemitamab; TST001
10.1.14 SPX-101
10.1.15 TORL-2-307-MAB
10.1.16 ZL-1211
10.1.17 Zolbetuximab
10.2 Antibody-Drug Conjugates
10.2.1 ATG-022
10.2.2 BA1301
10.2.3 CMG901
10.2.4 IBI343
10.2.5 JS107
10.2.6 LM-302; BMS-986476; TPX-4589
10.2.7 RC118
10.2.8 SHR-A1904
10.2.9 SKB315
10.2.10 SOT102
10.2.11 SYSA1801; EO-3021
10.2.12 TORL-2-307-ADC
10.3 Chimeric Antigen Receptor T-Cells
10.3.1 BNT212
10.3.2 CT041
10.3.3 CT048
10.3.4 GC506
10.3.5 IBI345
10.3.6 IMC002
10.3.7 KD-496
10.3.8 LB1908
10.3.9 LY011
10.3.10 PM3023
10.3.11 TAC01-CLDN18.2
10.4 Bispecific T-Cell Engaging Antibodies
10.4.1 ABP-150
10.4.2 ASP2138
10.4.3 GB264
10.4.4 Gresonitamab; AMG 910
10.4.5 HBM7022; AZD5863
10.4.6 IBI389
10.4.7 QLS31905
10.4.8 WB67
10.5 CLDN18.2 Targeted Bispecific Immuno-Oncology (I-O) Antibodies
10.5.1 CLDN18.2 x 4-1BB Bispecific Antibodies
10.5.1.1 FL-302; NBL-016
10.5.1.2 Givastomig
10.5.1.3 PM1032
10.5.2 CLDN18.2 x CD47 / SIRPα Bispecific Antibodies
10.5.2.1 BC007
10.5.2.2 ES028
10.5.2.3 PT886
10.5.3 CLDN18.2 x PD-L1 Bispecific Antibodies
10.5.3.1 Q-1802
10.5.3.2 TST006
11 References
ADDENDUM
Tables in the Text
Figures & Tables
Tables in the Text
Table 1 CLDN18.2 Tissue Expression in Cancer – Summary of Study Results
Table 2 Rights and Economic Terms of Licensing Agreements for CLDN18.2-Targeted Drug Candidates
Table 3 Overview of Major Biopharmaceutical Companies outside of China with CLDN18.2 Programs
Table 4 Overview of Other Biopharmaceutical Companies outside of China with CLDN18.2 Programs
Table 5 Overview of Chinese Biopharmaceutical Companies with Clinical Development of CLDN18.2 Programs outside of China
Table 6 Overview of Chinese Biopharmaceutical Companies with Clinical Development of CLDN18.2 Programs inside of China
Table 7 Overview of Chinese Biopharmaceutical Companies with Non-Clinical & Preclinical R&D of CLDN18.2 Programs
Table 8 Overview of Drug Modalities and R&D Stage of CLDN18.2-Targeted Immunotherapeutics in Active Development
Table 9 Discontinud CLDN18.2-Targeted Immunotherapeutics
Table 10 Naked Monoclonal Antibodies and their Fc Function
Table 11 Composition of Anti-CLDN18.2 Antibody-Drug Conjugates (ADCs)
Table 12 Autologous Anti-CLDN18.2 Chimeric Antigen Receptor T-cells
Table 13 CLDN18.2-Targeted Bispecific T-Cell Engaging Antibodies via CD3
Table 14 CLDN18.2-Targeted Immuno-Oncology (I-O) Bispecific Antibodies
Table 15 Astellas Pharma’s Pipeline of Claudin 18.2-Targeted Drug Candidates
Table 16 AstraZeneca’s CLDN18.2-Targeted Immunotherapy Franchise
Table 17 Claudin 18.2 Immunotherapy Franchise of BioNTech
Table 18 Integral Molecular’s Pipeline of CLDN18.2-Targeted Antibodies
Table 19 Integral Molecular’s Pipeline of CLDN18.2-Targeted Antibodies
Table 20 TORL Biotherapeutics’ Pipeline of CLDN18.2-Targeted Antibodies
Table 21 Pipeline of CARsgen Therapeutics’ Claudin 18.2 Franchise
Table 22 CLDN18.2-Targeted Immunotherapy Franchise of Innovent Biologics
Table 23 CLDN18.2-Targeted Immunotherapy Pipeline of Transcenta Holding
Table 24 CLDN18.2-Targeted Immunotherapy Pipeline of Biotheus
Table 25 CLDN18.2-Targeted Antibodies from CSPC Pharmaceutical Group
Table 26 CLDN18.2-Targeted Immunotherapy Pipeline of Nanjing Kaedi Biotherapeutics
Table 27 CLDN18.2-Targeted Immunotherapy Pipeline of Junshi Biosciences
Table 28 Zhejiang Biologics Pipeline of CLDN18.2-Targeted Antibodies
Table 29 CLDN18.2-Targeted Antibody Franchise of Dragon Boat Biopharmaceutical
Table 30 OriCell Therapeutic’s Pipeline of CLDN18.2-Targeted Bispecific Antibodies
Table 31 CLDN18.2-Targeted Immunotherapy Pipeline of Shanghai Genbase Biotechnology
Table 32 Clinical Development Program of Zolbetuximab in First-Line GC/GEJ Cancer