Claudin 18.2標的療法の世界市場：市場機会と臨床試験の考察 (2028年)

当レポートの分析結果と概略

• 最初のClaudin 18.2標的抗体が、2024年上半期までに商業的に発売される
• 臨床試験中のClaudin 18.2標的薬：60以上の薬剤
• 世界のClaudin 18.2標的薬の現在の市場傾向と動静
• Claudin 18.2標的薬の臨床試験情報：企業別、適応症別、相別
• Claudin 18.2療法開発のための技術的・臨床的プラットフォームに関する洞察
• Claudin 18.2標的療法の開発アプローチ：CAR T細胞療法、二重特異性抗体、抗体薬物複合体

がんには数多くのバイオマーカーが存在し、その多くは精密医療のターゲットとして利用されています。様々な有望ながんタンパク質の中でも、Claudin 18 (CLDN18) は治療上かなり有望な選択肢となっています。CLDN18の変異体であるCLDN18.2の出現により、特に注目されています。CLDN18.2の発現パターンは明瞭で、ほとんどが胃粘膜に存在します。この変異型はある種の悪性腫瘍との関連から注目されるようになっています。CLDN18の治療可能性に関する研究が進むにつれて、その医薬品領域への影響は大きくなり、いくつかのがんの治療法に革命をもたらす可能性があります。

CLDN18は、上皮細胞の密接接合と大きく関係しているタンパク質で、治療標的としての可能性から、最近多くの関心を集めています。CLDN18の主な利点の一つは、膵臓がん、胃がん、肺がんを含む様々な腫瘍で発現していることです。この選択的発現のため、精密医療のターゲットとして魅力的であり、悪性組織を破壊しながら健康な組織を保護する標的薬の創製を可能にします。したがって、多様な悪性腫瘍におけるCLDN18の過剰発現は、がん医薬品の領域においてユニークな機会を提供します。

さらに、がん治療標的としてのCLDN18.2の利用は、薬剤耐性を低下させるという点でも有望です。がんの原因となっている正確なタンパク質を特異的に標的とすることで、耐性メカニズムが発達しにくくなり、治療効果が高まる。したがって、CLDN18とCLDN18.2の可能性は、製薬業界にとっても見逃せないものです。

CLDN18を標的とするファースト・イン・クラスの治験用モノクローナル抗体であるゾルベツキシマブは、CLDN18.2陽性HER2陰性の胃がんまたは胃食道接合部がん患者のファーストライン治療薬として開発されています。ゾルベツキシマブの開発元であるアステラス製薬は2023年7月、FDAがゾルベツキシマブの生物製剤承認申請 (BLA) を承認し、優先審査権も付与したと発表しました。承認されれば、ゾルベツキシマブは米国で初めてCLDN18.2を標的とした抗がん剤となります。さらに、アステラス製薬は日本、欧州、中国でもゾルベツキシマブの承認申請を行っています。この薬剤は、胃がん、胃食道接合部腺がん、膵臓腺がんを対象とした複数の後期臨床試験で評価されています。

ゾルベツキシマブのような抗体以外に、CLDN18.2を標的とするキメラ抗原受容体T細胞 (CAR-T) 療法も開発中です。これらの細胞ベースの治療法は、CLDN18.2を発現するがんと闘うための最先端のアプローチです。CAR-T療法は、がん細胞を認識して攻撃するように、ドナーまたは患者由来のT細胞を遺伝子改変するもので、CLDN18.2を発現するがんに適用されれば、この治療法は大いに期待できます。例えば、青島大学附属病院では、Claudin 18.2を発現する再発または難治性の胃がんを対象に、iPD-1-Claudin 18.2-CAR-T療法XKDCT086の安全性と忍容性を評価するため、9人の参加者を得て臨床試験を実施しています。この新しいアプローチは、治療標的としてのClaudin18.2の適応性を強調するだけでなく、がん治療における精密医療の進化を強調するものです。

CLDN18.2を標的とした治療法は、がん治療における個別化治療の発展にも貢献しています。患者のCLDN18.2レベルに合わせてカスタマイズされた治療は、治療成績を大幅に改善する可能性があります。加えて、CLDN18またはCLDN18.2を標的とする治療法は、現在の治療法と併用することで、その有効性を高めることができる可能性があります。例えば、CLDN18を標的とする治療法と免疫療法との組み合わせは、強力ながん治療戦略であり、さらなる研究が必要です。

製薬会社は、CLDN18の市場激変の可能性を認識し、CLDN18研究に多額の資金を投じています。CLDN18に特化したベンチャー企業は、製薬セクターで将来性を求める投資家にとって魅力的かもしれないです。CLDN18を標的とした治療法に取り組む小規模製薬会社も、製薬市場で目立つようになってきています。例えばKYMバイオサイエンシズは、2023年2月に世界的製薬大手のアストラゼネカと、CLDN18.2を標的とする抗体薬物複合体CMG901の世界ライセンス契約を締結したと発表しました。アストラゼネカはCMG901の世界な研究開発、製造、商業化を担当します。契約によると、アストラゼネカはKYM社に対し、取引完了時に6,300万米ドルの契約一時金を支払うほか、さらなる研究および販売関連のマイルストーンとしてさらに11億米ドルを支払っています。

したがって、CLDN18とその変異体であるCLDN18.2は、製薬業界、特にがん治療における希望の光です。CLDN18は多くのがんに存在し、調査や臨床試験で有望な結果が得られていることから、その重要性が継続的に浮き彫りになっています。CLDN18は治療標的として魅力的な可能性を秘めており、がん治療へのアプローチ方法を変える可能性があります。

目次

第1章 Claudin 18.2療法 - がん治療の新時代

第2章 Claudin 18.2療法の概略

• Claudin 18.2タンパク質を理解する
• Claudin 18.2療法の経緯と動向

第3章 Claudin 18.2標的療法の必要性

第4章 がん免疫療法におけるClaudin 18.2をターゲットとした分析の進歩

• モノクローナル抗体療法
• 二重特異性抗体
• CAR-T細胞療法
• 抗体薬物複合体

第5章 胃がん・膵臓がんにおけるClaudin 18.2療法：臨床動向と革新

• 胃がん
• 膵臓がん

第6章 世界のClaudin 18.2市場：現在の傾向と動静

• 現在の市場動向の見通し
• 今後の市場の見通し

第7章 Claudin 18.2療法の動向分析：地域別

• 米国
• 中国
• 欧州
• 英国
• 日本
• オーストラリア
• 韓国

第8章 世界のClaudin 18.2医薬品の臨床試験の概要

• 企業別
• 国別
• 治療薬クラス別
• 適応症別
• 患者セグメント別
• 相別 (フェーズ別)

第9章 世界のClaudin 18.2医薬品の臨床試験：企業別・適応症別・相別

• 創薬
• 前臨床
• 第I相
• 第I/II相
• 第II相
• 登録前

第10章 高度Claudin 18.2療法を開発するための技術・臨床プラットフォーム

第11章 世界のClaudin 18.2治療市場力学

• 市場促進要因
• 市場の課題

第12章 競合情勢

• Abpro Therapeutics
• Antengene Corporation
• Arovella Therapeutics
• Astellas Pharma
• AstraZeneca
• Beijing Mabworks Biotech
• BioNTech
• Biotheus
• CARsgen
• Dragonboat Biopharmaceutical
• Gracell Biotechnology
• Harbour BioMed
• Innovent Biologics
• Integral Molecular
• Klus Pharma
• L and L Biopharma
• LaNova Medicines Limited
• Leap Therapeutics
• Luye Pharma Group
• Nanjing Bioheng Biotech
• Nanjing KAEDI Biotech
• NBE-Therapeutics
• OriCell Therapeutics
• Qilu Pharmaceutical
• Shanghai Junshi Biosciences
• Sparx Therapeutics
• Tillead Therapeutics
• TORL Biotherapeutics
• Transcenta Holding
• Zai Biopharmaceutical

List of Figures

• Figure 2-1: Function of Claudin 18.2 Protein
• Figure 2-2: Functional Classification of the Claudin Family Proteins
• Figure 2-3: Dichotomous Role of Claudin 18.2 Protein in Cancer
• Figure 2-4: Claudin 18 Isoforms
• Figure 3-1: Global - Gastric Cancer Incidences & Deaths (Million), 2020
• Figure 4-1: Therapeutic Approach for Claudin 18.2 protein
• Figure 4-2: mAb - Mode of Action
• Figure 4-3: Claudin 18.2 - Novel Monoclonal Antibodies in Clinical Research
• Figure 4-4: Advantage of Bispecific Antibodies
• Figure 4-5: PT886 - Phanes Therapeutics Development Vista
• Figure 4-6: Q-1802 Phase I/II Study - Initiation & Completion Year
• Figure 4-7: QLS31905 Phase I/II Study - Initiation & Completion Year
• Figure 4-8: ASP2138 - Astellas Pharma
• Figure 4-9: CARsgen Pharmaceuticals Collaboration - Fudan & Peking University for CT041 & CT048
• Figure 4-10: Immunofoco - Pipeline for Claudin 18.2 Therapy
• Figure 4-11: NCT06084286 Phase I Study - Initiation & Completion Year
• Figure 4-12: SKB315 - Clinical Trial & Collaboration Overview
• Figure 4-13: RC118 Phase I/I Study - Initiation & Completion Year
• Figure 4-14: Claudin 18.2 -ADCs Candidates
• Figure 5-1: Upregulation of Claudin 18.2 in Gastric Cancer
• Figure 5-2: HEC-016 Phase I Study - Initiation & Completion Year
• Figure 5-3: Structure & Mode of Action for TJ-CD4B
• Figure 5-4: Osemitamab Phase I/II Study - Initiation & Completion Year
• Figure 5-5: LY011 Phase I/II Study - Initiation & Completion Year
• Figure 5-6: SOT102 Phase I Study - Initiation & Completion Year
• Figure 5-7: KD-496 Phase I Study - Initiation & Completion Year
• Figure 5-8: SPX-101 Phase I Study - Initiation & Completion Year
• Figure 5-9: Zolbetuximab Phase II Study - Initiation & Completion Year
• Figure 6-1: Companies involved in Clinical Trial for Claudin 18.2 Therapy
• Figure 6-2: Global - Claudin 18.2 Target Therapy Market (US Million), 2024 - 2028
• Figure 6-3: Aspects Determining the Future of Claudin 18.2 Therapy
• Figure 7-1: TAC101-CLAUDIN 18.2 Phase I Study - Initiation & Completion Year
• Figure 7-2: Triumvira Immunologics - Pipeline for Claudin 18.2 Therapies
• Figure 7-3: TORL-2-307 Phase I Study - Initiation & Completion Year
• Figure 7-4: Aspects Influencing the Claudin 18.2 Therapy in US
• Figure 7-5: China - Major Candidates in Clinical Trial
• Figure 7-6: LM302 Phase II Study - Initiation & Completion Year
• Figure 7-7: Strategic Collaboration Between LaNova & Turning Point
• Figure 7-8: TQB2103 Phase I Study - Initiation & Completion Year
• Figure 7-9: CARsgen Therapeutics Pipeline for Claudin 18.2
• Figure 7-10: CT041 Phase II Study - Initiation & Completion Year
• Figure 7-11: NCT06084286 Phase I Study - Initiation & Completion Year
• Figure 7-12: SOT102 Phase I/II Study - Initiation & Completion Year
• Figure 7-13: AZD0901 Phase II Study - Initiation & Completion Year
• Figure 7-14: AZD0901 Phase II Study - Initiation & Completion Year
• Figure 7-15: CMG901 - Partnership Between AstraZeneca & KYM Bioscience
• Figure 7-16: Zolbetuximab - Reasons for Approval of Biologics License Application & Priority Designations
• Figure 7-17: SPOTLIGHT Phase III Study - Initiation & Completion Year
• Figure 7-18: GLOW Phase III Study - Initiation & Completion Year
• Figure 7-19: ASP2138 Phase I Study - Initiation & Completion Year
• Figure 7-20: Collaboration of SparX Group & Arovella Therapeutics for Claudin 18.2 iNKT cell therapy
• Figure 7-21: ATG-022 Phase I Study - Initiation & Completion Year
• Figure 8-1: Global - Claudin 18.2 Drugs Clinical Trials by Company (Numbers), 2023 till 2028
• Figure 8-2: Global - Claudin 18.2 Drugs Clinical Trials by Country (Numbers), 2023 till 2028
• Figure 8-3: Global - Claudin 18.2 Drugs Clinical Trials by Therapy Class (Numbers), 2023 till 2028
• Figure 8-4: Global - Claudin 18.2 Drugs Clinical Trials by Indication (Numbers), 2023 till 2028
• Figure 8-5: Global - Claudin 18.2 Drugs Clinical Trials by Patient Segment(Numbers), 2023 till 2028(Numbers), 2023 till 2028
• Figure 8-6: Global - Claudin 18.2 Drugs Clinical Trials by Phase (Numbers), 2023 till 2028
• Figure 10-1: CARsgen Pharmaceuticals - CycloCAR platform
• Figure 10-2: LaNova - LX-ADC™ Platform
• Figure 10-3: Phanes Therapeutics - PACbody
• Figure 10-4: Phanes Therapeutics - SPECpair
• Figure 11 1: Market Drivers for Claudin 18.2 Therapy
• Figure 11 2: Market Challenges for Claudin 18.2 Therapy

List of Tables

• Table 2-1: Subfamilies of Claudin involved in Different Types of Cancer Formation
• Table 4-1: Monoclonal Antibody Approaches Targeting Claudin 18.2 Protein
• Table 4-2: Bispecific Antibody Approaches Targeting Claudin 18.2 Protein
• Table 4-3: CAR-T Therapy Approaches Targeting Claudin 18.2 Protein
• Table 4-4: Antibody Drug Conjugate Approaches Targeting Claudin 18.2 Protein
• Table 5-1: Gastric Cancer - Ongoing Clinical Trials For Claudin 18.2 Therapy
• Table 7-2: US - Ongoing Clinical Trial for Claudin 18.2 Therapy
• Table 7-1: China - Ongoing Clinical Trials for Claudin 18.2 Therapy
• Table 7-3: EU - Ongoing Clinical Trial for Claudin 18.2 Therapy
• Table 7-5: UK- Ongoing Clinical Trial for Claudin 18.2 Therapy
• Table 7-4: Japan - Ongoing Clinical Trial for Claudin 18.2
• Table 7-6: Australia - Ongoing Clinical Trial for Claudin 18.2
• Table 7-7: South Korea - Ongoing Clinical Trial for Claudin 18.2

“Global Claudin 18.2 Targeted Therapy Market Opportunity & Clinical Trials Insight 2028” Report Findings & Highlights:

• First Claudin 18.2 Targeting Antibody Commercial Launch By H1 2024
• Claudin 18.2 Targeted Drugs In Clinical Trials: > 60 Drugs
• Global Claudin 18.2 Current Market Trend & Developments
• Global Claudin 18.2 Drugs Clinical Trials By Company, Indication & Phase
• Insight On Technical & Clinical Platforms For Developing Claudin 18.2 Therapy
• Claudin 18.2 Targeted Therapy Development Approaches: CAR T Cell Therapy, Bispecific Antibodies, Antibody Drug Conjugates

Cancer is marked by the presence of numerous biomarkers, many of which are being used as targets for precision medicine. Among the various promising cancer proteins, Claudin-18 (CLDN18) has become a compelling option with considerable therapeutic promise. Particular attention has been aroused by the emergence of CLDN18.2, a variation of CLDN18. The expression pattern of CLDN18.2 is distinct and it is mostly present in the gastric mucosa. This variant has gained prominence due to its association with certain malignancies. As investigations into the therapeutic potential of CLDN18 continue, its impact on the pharmaceutical domain is poised to be substantial, potentially revolutionizing the way we treat some cancers.

CLDN18, a protein that is largely linked with tight junctions in epithelial cells, has received a lot of interest recently because of its potential as a therapeutic target. One of its key advantages is that it is expressed in a variety of tumors, including pancreatic, gastric and lung cancers. Because of this selective expression, it is an appealing target for precision medicine, enabling the creation of targeted medicines that protect healthy tissues while destroying malignant tissues. Therefore, CLDN18 overexpression in diverse malignancies offers a unique opportunity in the realm of cancer pharmaceuticals.

In addition, the usage of CLDN18.2 as a cancer therapeutic target has also showed promise in terms of lowering drug resistance. Resistance mechanisms are less likely to develop when the exact protein responsible for the cancer is specifically targeted, boosting the effectiveness of treatment. Therefore, loaded with several benefits, the potential of CLDN18 and CLDN18.2 has not clearly not gone unnoticed by the pharmaceutical sector.

Zolbetuximab, a first-in-class investigational monoclonal antibody designed to target the CLDN18, is being developed for the first-line treatment of patients with gastric or gastroesophageal junction cancer that is CLDN18.2-positive HER2-negative. Astellas, the developer of Zolbetuximab, announced in July 2023 that the FDA had approved their biologics license application (BLA) for Zolbetuximab, also granting it a priority review. If approved, Zolbetuximab will become the first CLDN18.2-targetd drug to become available in the US for these patients. In addition, Astellas has also filed applications for Zolbetuximab approval in Japan, Europe and China. The drug is being evaluated in multiple late-phase clinical trials in gastric and gastroesophageal junction adenocarcinoma and pancreatic adenocarcinoma.

Apart from antibodies like Zolbetuximab, chimeric antigen receptor T-cell (CAR-T) therapies targeting CLDN18.2 are also under development. These cell-based therapies represent a cutting-edge approach to combating cancers that express CLDN18.2 CAR-T therapy involves the genetic modification of donor or patient-derived T cells to recognize and attack cancer cells, and when applied to CLDN18.2-expressing cancers, the therapy holds great promise. For instance, the Affiliated Hospital of Qingdao University is conducting a clinical trial with 9 participants to assess the safety and tolerability of iPD-1-Claudin18.2-CAR-T therapy, XKDCT086, in recurrent or refractory gastric cancer expressing Claudin18.2. This novel approach not only highlights the adaptability of Claudin18.2 as a therapeutic target but also underscores the evolving nature of precision medicine in the treatment of cancer.

CLDN18.2-targeted therapies have also aided the growth of personalized therapies in cancer treatment. Treatments customized to the patient's CLDN18.2 levels could improve treatment outcomes significantly. In addition, therapies that target CLDN18 or CLDN18.2 can potentially be used in combination with current therapies to boost their efficacy. For instance, pairing CLDN18-targeted therapies with immunotherapies represents a powerful cancer treatment strategy that requires further investigation.

Pharmaceutical companies are heavily spending on CLDN18 research, realizing its market upheaval potential. CLDN18-focussed ventures may be appealing to investors looking for prospects in the pharmaceutical sector. Small pharmaceutical companies working on CLDN18-targeting therapies are also becoming more visible in the pharmaceutical market. KYM Biosciences, for example, announced a global license agreement with global pharma giant AstraZeneca in February 2023 for its CLDN18.2 targeting antibody-drug conjugate CMG901, the first of its kind. AstraZeneca will be responsible for the global research, development, manufacturing and commercialization of CMG901. According to the agreement, AstraZeneca will pay KYM an upfront payment of US$ 63 million upon closing of the transaction, as well as another US$ 1.1 billion on further research and sales-related milestones.

Therefore, CLDN18 and its variant CLDN18.2 are a ray of hope in the pharmaceutical industry, especially cancer therapy. Its prevalence in numerous cancers as well as encouraging outcomes from research investigations and clinical trials have continuously highlighted its importance. CLDN18 has a fascinating potential as a therapeutic target and could potentially alter the way we approach cancer therapy.

Table of Contents

1. Claudin 18.2 Therapy - New Epoch For Cancer Treatment

2. Introduction To Claudin 18.2 Therapy

• 2.1. Understanding Claudin 18.2 Proteins
• 2.2. Chronicle & Development of Claudin 18.2 Therapy

3. Need For Claudin 18.2 Targeted Therapy

4. Research Advancement Targeting Claudin 18.2 For Cancer Immunotherapy

• 4.1. Monoclonal Antibody Therapy
• 4.2. Bispecific Antibody
• 4.3. CAR T Cell Therapy
• 4.4. Antibody Drug Conjugate

5. Claudin 18.2 Therapy In Gastric & Pancreatic Cancer: Clinical Trends & Innovations

• 5.1. Gastric Cancer
• 5.2. Pancreatic Cancer

6. Global Claudin 18.2 Current Market Trend & Developments

• 6.1. Current Market Development Outlook
• 6.2. Future Market Outlook

7. Claudin 18.2 Therapy Trend Analysis By Region

• 7.1. US
• 7.2. China
• 7.3. Europe
• 7.4. UK
• 7.5. Japan
• 7.6. Australia
• 7.7. South Korea

8. Global Claudin 18.2 Drugs Clinical Trials Overview

• 8.1. By Company
• 8.2. By Country
• 8.3. By Therapy Class
• 8.4. By Indication
• 8.5. By Patient Segment
• 8.6. By Phase

9. Global Claudin 18.2 Drugs Clinical Trials By Company, Indication & Phase

• 9.1. Research
• 9.2. Preclinical
• 9.3. Phase-I
• 9.4. Phase-I/II
• 9.5. Phase-II
• 9.6. Preregistration

10. Technical & Clinical Platforms For Developing Advanced Claudin 18.2 Therapy

11. Global Claudin 18.2 Therapy Market Dynamics

• 11.1. Market Drivers
• 11.2. Market Challenges

12. Competitive Landscape

• 12.1. Abpro Therapeutics
• 12.2. Antengene Corporation
• 12.3. Arovella Therapeutics
• 12.4. Astellas Pharma
• 12.5. AstraZeneca
• 12.6. Beijing Mabworks Biotech
• 12.7. BioNTech
• 12.8. Biotheus
• 12.9. CARsgen
• 12.10. Dragonboat Biopharmaceutical
• 12.11. Gracell Biotechnology
• 12.12. Harbour BioMed
• 12.13. Innovent Biologics
• 12.14. Integral Molecular
• 12.15. Klus Pharma
• 12.16. L and L Biopharma
• 12.17. LaNova Medicines Limited
• 12.18. Leap Therapeutics
• 12.19. Luye Pharma Group
• 12.20. Nanjing Bioheng Biotech
• 12.21. Nanjing KAEDI Biotech
• 12.22. NBE-Therapeutics
• 12.23. OriCell Therapeutics
• 12.24. Qilu Pharmaceutical
• 12.25. Shanghai Junshi Biosciences
• 12.26. Sparx Therapeutics
• 12.27. Tillead Therapeutics
• 12.28. TORL Biotherapeutics
• 12.29. Transcenta Holding
• 12.30. Zai Biopharmaceutical