表紙:プロドラッグとしてのマスクされた抗体とサイトカイン市場:業界の視点から見たステークホルダー、技術、パイプライン、ビジネス、資金調達動向
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商品コード
1031041

プロドラッグとしてのマスクされた抗体とサイトカイン市場:業界の視点から見たステークホルダー、技術、パイプライン、ビジネス、資金調達動向

Masked Antibodies & Cytokines as Prodrugs: A Landscape Analysis of Stakeholders, Technologies, Pipelines, Business and Financing from an Industry Perspective

出版日: | 発行: La Merie Publishing | ページ情報: 英文 433 Pages | 納期: 即日から翌営業日

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本日の銀行送金レート: 1EUR=133.46円
プロドラッグとしてのマスクされた抗体とサイトカイン市場:業界の視点から見たステークホルダー、技術、パイプライン、ビジネス、資金調達動向
出版日: 2021年10月03日
発行: La Merie Publishing
ページ情報: 英文 433 Pages
納期: 即日から翌営業日
  • 全表示
  • 概要
  • 図表
  • 目次
概要

抗体医薬品は、臨床的にも商業的にも成功した治療法となっており、2020年には100以上の抗体医薬品が治療薬として承認され、商業的な売上高は1,840億米ドルを超えると言われています。しかし、モノクローナル抗体やサイトカインを全身に投与すると、作用機序の影響、つまり健康な組織におけるオフターム・オンタームの毒性を伴う重篤な有害事象が誘発される可能性があります。疾患部位における抗体やサイトカインの選択性を高めるためには、抗体は標的抗原を、サイトカインは正常な健常組織の受容体を無視して、疾患部位で優先的に活性化することが必要です。

抗体プロドラッグの使用は、生物学的療法のより特異的な腫瘍ターゲティングのための新しい戦略の一つです。従来のプロドラッグは、薬理学的に不活性な化合物で、投与後に体内で活性型に変換されます。意図した作用部位で活性化するように設計することで、正常組織への活性薬物の暴露を抑え、毒性を最小限に抑えることができます。抗体プロドラッグの最も一般的な手法は、抗原結合部位の「マスク」を用いたプロテアーゼ活性化抗体です。マスクは通常、抗体の軽鎖および/または重鎖を拡張したリコンビナントタンパク質であり、抗原結合部位へのアクセスを遮断し、同族抗原への抗体の結合を物理的に阻止するように設計されています。また、マスクと抗体の間にはプロテアーゼ基質配列が挿入されています。プロドラッグ抗体が腫瘍の微小環境に入ると、癌組織に多く見られる高発現プロテアーゼが基質配列を切断し、マスクが抗体から分離し、抗体は腫瘍内の標的に結合するようになります。正常組織では、細胞外のプロテアーゼ活性が十分でないため、このようなことは効率的に起こりません。この原理は、プロドラッグサイトカインにも当てはまります。

当レポートでは、プロドラッグとしてのマスクされた抗体とサイトカイン市場について調査し、40のステークホルダーの概要、企業の背景や歴史、財務状況、関連技術、提携案件、ターゲットとパイプラインの概要などの情報を提供するプロファイルなどを提供しています。

目次

略語

第1章 エグゼクティブサマリー

第2章 イントロダクション、概要と調査手法

第3章 ステークホルダー分析

  • 概要
  • マスキング技術企業
  • マスキング技術企業と提携した製薬会社/バイオ技術企業

第4章 マスキング技術におけるステークホルダープロファイル

  • マスキング技術企業のプロファイル
  • マスキング技術に関与する製薬およびバイオ技術企業のプロファイル

第5章 マスキング技術の分析

  • マスキング技術の起源
  • プロドラッグ抗体技術
  • プロドラッグサイトカイン技術
  • プロドラッグ抗体およびサイトカイン技術

第6章 マスキング技術のプロファイル

  • 抗体にのみ適用されるマスキング技術
  • サイトカインにのみ適用されるマスキング技術
  • Trutino Biosciences:オンデマンド-サイトカイン(ODC)プラットフォーム
  • Werewolf Therapeutics:PREDATOR技術プラットフォーム
  • 抗体およびサイトカインに適用されるマスキング技術

第7章 パイプラインおよびマスクされた抗体およびサイトカインプロドラッグ候補分析

  • イントロダクション
  • マスクされた抗体のパイプライン分析
    • マスクされた抗体パイプラインの概要
    • EGFRを標的としたパイプライン
    • CTLA4を標的としたパイプライン
    • EpCAMを標的としたパイプライン
    • Her2を標的としたパイプライン
    • TROP2、PSMAまたはB7-H3を標的としたパイプライン
    • その他のパイプライン
    • 機序と概念の臨床的証明
  • マスクされたサイトカインのパイプライン分析
    • マスクされたインターロイキン2分子のパイプライン
    • マスクされたインターロイキン-12および-15分子のパイプライン
    • マスクされたインターフェロンアルファ分子のパイプライン

第8章 マスクされた抗体およびサイトカイン製品候補プロファイル

  • マスクされた免疫腫瘍学抗体
    • ADG126
    • 抗CD47プロドラッグ抗体
    • BA3071
    • BMS-986249
    • BMS-986288
    • CX-188
    • パクミリマブ
    • PD-L1 xCD28共刺激二重特異性
    • XTX101
  • マスクされた抗体-薬物複合体
    • CX-2029
    • CX-2043
    • メコボタマブベドチン
    • オズリフタマブベドチン
    • プラルザタマブラブタンシン
  • マスクされたT細胞エンゲージメント(TCE)抗体
    • AMX-818
    • BA3182
    • CX-904
    • EGFR-TRACTr
    • EGFR-XPAT
    • Her2-PROTECT-CD3
    • HPN601
    • PSMA-TRACTr
    • TAK-186
    • TAK-280
    • TROP2-TRACTr
  • マスクされたインターロイキン-2(IL-2)サイトカイン
    • ベンペガルデスロイキン
    • ODC-IL2
    • TransConIL-2β/γ(ベータ/ガンマ)
    • WTX-124
    • XTX202
  • マスクされたインターロイキン-12(IL-12)および-15(IL-15)サイトカイン
    • ASKG215β(ベータ)およびASKG215γ(ガンマ)
    • IL-12Fcを保護する
    • WTX-330
  • マスクされたインターフェロン(IFN)サイトカイン
    • デュアルマスクインターフェロンα2b(alpha2b)
    • WTX-613

第9章 ビジネス、資金調達、パートナーシップ

  • 仕事
  • 資金調達
  • 提携

第10章 参考文献

補遺:マスクされた抗体およびサイトカインの競合分析

図表

List of Tables

  • Table 1: Corporate Stakeholders in Masking Technologies
  • Table 2: Focus of Masking Technology Companies
  • Table 3: Profiles of Companies with Masking Technologies
  • Table 4: Interests of Pharma/Biotech Companies in Applications of Masking Technologies
  • Table 5: Partnerships between Masking Technology Companies and Pharma/Biotech Companies
  • Table 6: Levels of Interest and Participation of Major Pharma/Biotech Companies in Masking Technologies
  • Table 7: Adagene’s Partnered SAFEbody Discovery Programs
  • Table 8: Adagene’s SAFEbody Pipeline
  • Table 9: Amunix Pharmaceuticals’ Unpartnered Pipeline of XPATs and XPACs
  • Table 10: BioAtla’s Pipeline of Conditionally Active Biologics (CABs)
  • Table 11: Pipeline of Proprietary and Partnered Probody Therapeutics from CytomX Therapeutics
  • Table 12: TRACTr & TRACIr Pipeline of Janux Therapeutics
  • Table 13: Maverick Therapeutics’ Pipeline of COBRA Molecules
  • Table 14: Werewolf Therapeutics’ Pipeline of Indukine Molecules
  • Table 15: Xilio Therapeutics’ Pipeline of Masked Antibodies and Cytokines
  • Table 16: Source of Technology and Pharma Partners of Foundational Masking Technology Companies
  • Table 17: Foundational & Main Technology Platforms of Companies with Evolution to Masking Technologies
  • Table 18: Overview of Applications of Masking Technologies to Different Antibody Constructs
  • Table 19: Characteristics of the Masking Moiety Used for Generation of Prodrug Antibodies
  • Table 20: Characteristics of the Linker Moiety Used for Generation of Prodrug Antibodies
  • Table 21: Overview of Applications of Masking Technologies to Different Cytokines
  • Table 22: Characteristics of the Masking Moiety Used for Generation of Prodrug Cytokines
  • Table 23: Characteristics of the Linker Moiety Used for Generation of Prodrug Cytokines
  • Table 24: Overview of Applications of Masking Technologies to Different Cytokines & Antibody Constructs
  • Table 25: Characteristics of the Masking Moiety Used for Generation of Prodrug Antibodies & Cytokines
  • Table 26: Characteristics of the Linker Moiety Used for Generation of Prodrug Antibodies & Cytokines
  • Table 27: Overview of Masked Antibody R&D Programs
  • Table 28: Overview of Antibody Modality and R&D Stage of Masked Antibodies
  • Table 29: Overview of Antibody Modality and Targets of Masked Antibodies
  • Table 30: EGFR-Targeted Masked Antibody Programs in R&D
  • Table 31: CTLA4-Targeted Masked Antibody Programs in R&D
  • Table 32: EpCAM-Targeted Masked Antibody Programs in R&D
  • Table 33: Her2-Targeted Masked Antibody Programs in R&D
  • Table 34: Masked Antibody Programs Targeting TROP2, PSMA or B7-H3
  • Table 35: Pipeline of Other Masked Antibodies with Designated Targets
  • Table 36: Synopsis of Clinical Results of Masked Antibodies
  • Table 37: Overview of Masked Cytokine Programs in R&D
  • Table 38: Overview of Type of Cytokine and R&D Stage for Masked Cytokines
  • Table 39: Overview of Masked Interleukin-2 Programs in R&D
  • Table 40: Overview of Masked Interleukin-12 & -15 Programs in R&D
  • Table 41: Overview of Masked Cytokine Programs in R&D
  • Table 42: Financing of Converted Pure Play Masking Technology Companies
  • Table 43: Financing of Foundational Pure Play Masking Technology Companies
  • Table 44: Financial Terms of Partnering Deals Based on Masking Technology
目次
Product Code: LMFR00334

This report provides you with a landscape description and analysis of prodrug antibodies and cytokines employing conventional and novel masking technology platforms from an industry perspective as of October 2021.

The prodrug concept of masking technologies is an elegant approach to address the selectivity limitations of conventional therapeutic antibodies and cytokines.

The report brings you up-to-date with information about and analysis of

  • Stakeholders in the field: technology and major pharmaceutical companies and investors;
  • Masking technologies: conventional (kinetically controlled); pH dependent and protease cleavage in the tumor microenvironment
  • Targets of masked antibodies and type of masked cytokine selected for development of masked biologics;
  • Business strategy: pure play (foundational or converted) masking technology company, diversified technology company, exit options, preferred antibody modality or type of cytokine, investment case;
  • Financing situation of technology companies and key investors in the field;
  • Partnering deals with financial terms;
  • Major pharmaceutical companies: preferences for masking technologies, collaboration and licensing agreements.

Background

Therapeutic antibodies have become a clinically and commercially successful treatment modality with more than 100 antibodies approved for therapy and commercial sales of more than US$ 184 bln in the year 2020. However, systemic administration of monoclonal antibodies or cytokines may induce severe adverse events with mechanism-of-action effects, meaning off-tumor on-target toxicity in healthy tissue. In order to increase the selectivity of antibodies and cytokines at the disease site, antibodies should ignore the target antigen and cytokines the receptor in normal healthy tissue and be preferentially active in the disease region.

The use of antibody prodrugs is one new strategy for more specific tumor targeting of biological therapies. Conventional prodrugs are pharmacologically inactive compounds that are converted into active forms in the body after administration. They can be designed to be activated at the intended site of action, thereby lowering exposure of normal tissues to active drug and minimizing toxicity. The most common novel approach to creating antibody prodrugs are protease-activated antibodies that use antigen binding site 'masks'. The mask is typically a recombinant protein extension of the light and/or heavy chain of the antibody that has been designed to block access to the antigen binding site and physically prevent binding of the antibody to the cognate antigen. A protease substrate sequence is also inserted between the mask and the antibody. When the prodrug antibody enters the tumor microenvironment, upregulated proteases that are common in cancer tissues cleave the substrate sequence, the mask separates from the antibody, and the antibody becomes competent to bind to its target in the tumor. This doesn't happen efficiently in normal tissues because there is insufficient extracellular protease activity to remove the mask. The same principle does apply to prodrug cytokines.

Methodology

This report evaluates the industry landscape of masked antibodies and cytokines in research and development. The report is based on the identification and description of 40 stakeholder, 24 of which are companies with masking technologies and 16 are pharma/biotech companies partnered with masking technology companies.

For each masking technology company, a profile has been elaborated providing information about the company background/history, the financial situation, relevant technology, partnering deals and target & pipeline overview. Short profiles are provided for pharma & biotech companies with a stake in masking technologies. The company profiles are preceded by a chapter of stakeholder analysis.

Profiles of 20 different masking technologies were also elaborated and presented separately for masking technology onloy applied to antibodies, only applied to cytokines and applied to both, antibodies and cytokines. The masking technologies are analyzed with special focus on origin of technology, inactivation domain, linkers and substrates for protease cleavage. Conventional and universal masking technologies are also discussed.

Eventually, profiles of 25 masked antibody R&D programs and of 10 masked cytokine programs. Each masked antibody profile was assigned to one of three groups: immuno-oncology antibodies; antibody-drug conjugates (ADC) and T-cell engaging (TCE) bi- or trispecific antibodies. Masked cytokine profiles are presented separately for interleukin-2 (IL-2); IL-12 & IL-15; and interferon alpha. Discussion of the masked antibody programs includes applied masking technology, targets or type of cytokine, stage of development, preclinical and clinical experience.

In a separate chapter, aspects of business models, financing and partnering are presented and discussed. Further stakeholders of masking technologies include investment firms which are presented by company and investment round. Financial terms of partnering deals are also described and discussed.

All information in the three chapters of Company Profiles, Technology Profiles and Drug Candidate Profiles are fully referenced with 79 scientific references, in many cases with hyperlinks leading to the source of information (abstracts, Posters, papers). Non-scientific references, such as press releases, annual reports or company presentations, are disclosed within the text with an embedded hyperlink leading to the online source of information. Details about R&D strategy, collaboration and licensing agreements, financing rounds & sources are described in the company profiles.

The report further includes 35 tables to summarize and directly compare information and uses illustrations to explain principles of masking technologies.

What will you find in the report?

  • Profiles of antibody & cytokine masking technology companies active in the field;
  • Description of major pharma's/biotech's role in the field (in-house R&D, partnering and investing);
  • Comprehensive description and analysis of emerging masked antibodies and cytokines;
  • Pharmacologic profiles of selected masked antibodies and cytokines;
  • Characterization, profiling and state of antibody & cytokine masking technologies;
  • Target selection for each antibody masking technology;
  • Selection of type of cytokine for each cytokine masking technology;
  • 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 Stakeholder Analysis

  • 3.1 Overview
  • 3.2 Masking Technology Companies
  • 3.3 Pharma/Biotech Companies Partnered with Masking Technology Companies

4 Profiles of Stakeholders in Masking Technologies

  • 4.1 Profiles of Masking Technology Companies
    • 4.1.1 Accurus Bioscience
    • 4.1.2 Adagene
    • 4.1.3 Amunix Pharmaceuticals
    • 4.1.4 Ascendis Pharma
    • 4.1.5 AskGene Pharma
    • 4.1.6 BioAtla
    • 4.1.7 Bright Peak Therapeutics
    • 4.1.8 CytomX Therapeutics
    • 4.1.9 GlycoNEX
    • 4.1.10 Harpoon Therapeutics
    • 4.1.11 Janux Therapeutics
    • 4.1.12 Maverick Therapeutics
    • 4.1.13 Meditope Biosciences
    • 4.1.14 Molecular Partners
    • 4.1.15 Nektar Therapeutics
    • 4.1.16 Revitope Oncology
    • 4.1.17 SeaGen
    • 4.1.18 Shanghai Affinity Biopharmaceutical
    • 4.1.19 Tansoar Biotech
    • 4.1.20 Trutino Biosciences
    • 4.1.21 Werewolf Therapeutics
    • 4.1.22 Xilio Therapeutics
    • 4.1.23 Zymeworks
  • 4.2 Profiles of Pharma & Biotech Companies with a Stake in Masking Technologies
    • 4.2.1 AbbVie
    • 4.2.2 ADC Therapeutics
    • 4.2.3 Amgen
    • 4.2.4 Astellas Pharma
    • 4.2.5 BeiGene
    • 4.2.6 Boehringer Ingelheim
    • 4.2.7 Bristol Myers Squibb
    • 4.2.8 Exelixis
    • 4.2.9 I-Mab Biopharma
    • 4.2.10 Immunogen
    • 4.2.11 Janssen
    • 4.2.12 Junshi Biosciences
    • 4.2.13 Merck
    • 4.2.14 Mitsubishi Tanabe Pharma
    • 4.2.15 Pfizer
    • 4.2.16 Roche
    • 4.2.17 Takeda Pharmaceutical Co

5 Analysis of Masking Technologies

  • 5.1 Origin of Masking Technologies
  • 5.2 Prodrug Antibody Technologies
  • 5.3 Prodrug Cytokine Technologies
  • 5.4 Prodrug Antibody & Cytokine Technologies

6 Profiles of Masking Technologies

  • 6.1 Masking Technologies Applied Only To Antibodies
    • 6.1.1 Adagene: SAFEbody Technology
    • 6.1.2 BioAtla: Conditionally Active Biologics (CAB)
    • 6.1.3 Harpoon Therapeutics: ProTriTAC Technology
    • 6.1.4 Janux Therapeutics: Tumor Activated T Cell Engager (TRACTr) Technology
    • 6.1.5 Maverick Therapeutics: COBRA Technology
    • 6.1.6 Molecular Partners: Anti-CD3 ProDrug DARPin (CD3-PDD) Technology
    • 6.1.7 Revitope Oncology: PrecisionGATE Technology Platform
    • 6.1.8 Roche: Protease-Activated T-Cell Bispecific (TCB) Antibodies
    • 6.1.9 SeaGen: Coiled-Coil Masking Domain Technology
    • 6.1.10 Tansoar Biotech: Universal Antibody Lock Technology
  • 6.2 Masking Technologies Applied Only To Cytokines
    • 6.2.1 Ascendis Pharma: TransCon Technology
    • 6.2.2 AskGene Pharma: Smartkine Prodrug Technology
    • 6.2.3 Meditope Biosciences: SnAP Technology
    • 6.2.4 Nektar Therapeutics: Kinetically Controlled Prodrug Technology
  • 6-2.5 Trutino Biosciences: On-Demand-Cytokine (ODC) Platform
    • 6.2.6 Werewolf Therapeutics: PREDATOR Technology Platform
  • 6.3 Masking Technologies Applied to Antibodies & Cytokines
    • 6.3.1 Amunix Pharmaceuticals: Pro-XTEN Technology
    • 6.3.2 CytomX Therapeutics: Probody Technology
    • 6.3.3 Xilio Therapeutics: Geographically Precise Solutions (GPS) platform
    • 6.3.4 Zymeworks: PROTECT Technology Platform

7 Analysis of Pipeline and Masked Antibody & Cytokine Prodrug Candidates

  • 7.1 Introduction
  • 7.2 Analysis of the Pipeline of Masked Antibodies
    • 7.2.1 Overview of the Masked Antibody Pipeline
    • 7.2.2 Pipeline of EGFR-Targeted Masked Antibodies
    • 7.2.3 Pipeline of CTLA4-Targeted Masked Antibodies
    • 7.2.4 Pipeline of EpCAM-Targeted Masked Antibodies
    • 7.2.5 Pipeline of Her2-Targeted Masked Antibodies
    • 7.2.6 Pipeline of Masked Antibodies Targeting TROP2, PSMA or B7-H3
    • 7.2.7 Pipeline of Other Masked Antibodies with Designated Targets
    • 7.2.8 Clinical Proof of Mechanism and Concept
  • 7.3 Analysis of the Pipeline of Masked Cytokines
    • 7.3.1 Pipeline of Masked Interleukin-2 Molecules
    • 7.3.2 Pipeline of Masked Interleukin-12 and -15 Molecules
    • 7.3.3 Pipeline of Masked Interferon alpha Molecules

8 Profiles of Masked Antibody & Cytokine Product Candidates

  • 8.1 Masked Immuno-Oncology Antibodies
    • 8.1.1 ADG126
    • 8.1.2 Anti-CD47 Prodrug Antibody
    • 8.1.3 BA3071
    • 8.1.4 BMS-986249
    • 8.1.5 BMS-986288
    • 8.1.6 CX-188
    • 8.1.7 Pacmilimab
    • 8.1.8 PD-L1 x CD28 Costimulatory Bispecific
    • 8.1.9 XTX101
  • 8.2 Masked Antibody-Drug Conjugates
    • 8.2.1 CX-2029
    • 8.2.2 CX-2043
    • 8.2.3 Mecbotamab vedotin
    • 8.2.4 Ozuriftamab vedotin
    • 8.2.5 Praluzatamab ravtansine
  • 8.3 Masked T-Cell Engaging (TCE) Antibodies
    • 8.3.1 AMX-818
    • 8.3.2 BA3182
    • 8.3.3 CX-904
    • 8.3.4 EGFR-TRACTr
    • 8.3.5 EGFR-XPAT
    • 8.3.6 Her2-PROTECT-CD3
    • 8.3.7 HPN601
    • 8.3.8 PSMA-TRACTr
    • 8.3.9 TAK-186
    • 8.3.10 TAK-280
    • 8.3.11 TROP2-TRACTr
  • 8.4 Masked Interleukin-2 (IL-2) Cytokines
    • 8.4.1 Bempegaldesleukin
    • 8.4.2 ODC-IL2
    • 8.4.3 TransCon IL-2 β/γ (beta/gamma)
    • 8.4.4 WTX-124
    • 8.4.5 XTX202
  • 8.5 Masked Interleukin-12 (IL-12) and -15 (IL-15) Cytokines
    • 8.5.1 ASKG215 β (beta) and ASKG215 γ (gamma)
    • 8.5.2 ProTECT IL-12 Fc
    • 8.5.3 WTX-330
  • 8.6 Masked Interferon (IFN) Cytokines
    • 8.6.1 Dual Masked Interferon α 2b (alpha2b)
    • 8.6.2 WTX-613

9 Business, Financing & Partnering

  • 9.1 Business
  • 9.2 Financing
  • 9.3 Partnering

10 References

ADDENDUM: Competitor Analysis of Masked Antibodies & Cytokines