レポートバンドル - クローディン6、CDH17、ROR1、GPRC5D標的治療市場：標的発現プロファイル、薬物モダリティの安全性と有効性、パイプラインレビュー、および競合情勢の分析

当レポートでは、クローディン6、CDH17、ROR1、GPRC5D標的治療市場について調査し、市場の概要とともに、それぞれの臨床動向、適応症と患者動向、および市場に参入する企業の競合情勢など、4つのテーマ別市場調査レポートをセットにしてお届けいたします。

目次

クローディン6：エフェクター強化薬物モダリティを開発するための標的機会

第1章 標的の背景

第2章 標的抗原発現プロファイル

第3章 前臨床の概念実証

第4章 CLDN6を標的とした薬物モダリティの臨床経験

第5章 臨床適応症と患者集団

第6章 競合情勢と薬物モダリティ

第7章 薬物および細胞治療の候補薬プロファイル

• CARTセル
• 抗体薬物複合体（ADC）
• T細胞リダイレクト二重特異性抗体
• T細胞活性化二重特異性抗体
• 失敗に終わった薬物モダリティ

第8章 企業プロファイル

第9章 参考文献

CDH17：エフェクター強化薬物モダリティを開発するための標的機会

第1章 標的の背景

第2章 標的抗原発現プロファイル

第3章 前臨床の概念実証

第4章 臨床適応症と患者集団

第5章 競合情勢と薬物モダリティ

第6章 薬物および細胞治療の候補薬プロファイル

• CARTセル
• アポトーシス促進性二重特異性抗体
• T細胞リダイレクト二重特異性抗体
• 裸の抗体

第7章 企業プロファイル

第8章 参考文献

ROR1標的療法：標的発現プロファイル、薬物モダリティの安全性と有効性、パイプラインレビュー、および競合情勢環境

第0章 エグゼクティブサマリー

第1章 標的の背景：構造と機能

第2章 標的抗原発現プロファイル

• 血液悪性腫瘍
• さまざまな固形腫瘍
• 肺癌
• 膵臓癌
• 大腸癌
• 乳癌
• 卵巣癌

第3章 ROR1を標的とした治療薬候補の前臨床安全性

第4章 ROR1を標的とした薬物モダリティの臨床経験

第5章 臨床適応症と患者集団

• 慢性リンパ性白血病
• マントル細胞リンパ腫
• びまん性大細胞型B細胞リンパ腫
• トリプルネガティブ乳癌

第6章 競合情勢と薬物モダリティ

• ROR1を標的とした抗体薬物複合体
• T細胞エンゲージング抗ROR1抗体
• ROR1を標的としたCART細胞とNK細胞別養子細胞療法
• ROR1小分子阻害剤

第7章 薬物および細胞治療の候補薬プロファイル

• 裸の抗体
• 抗体薬物複合体
• T細胞が関与する二重特異性抗体
• CART細胞とNK細胞
• 小分子阻害剤

第8章 企業プロファイル

第9章 参考文献

GPRC5D-標的療法：標的発現プロファイル、薬物モダリティの安全性と有効性、パイプラインレビュー、および競合情勢分析

第1章 GPRC5DmRNAおよびタンパク質発現プロファイル

第2章 前臨床の有効性と安全性

第3章 GPRC5Dを標的とした薬物モダリティの臨床的有効性と安全性

第4章 対象患者集団

第5章 競合情勢と薬物モダリティ

第6章 抗体および細胞治療の候補薬プロファイル

• 抗体ベースの薬物モダリティ
• 細胞ベースの薬物モダリティ

第7章 企業プロファイル

第8章 参考文献

This report bundle includes four reports about novel cancer targets which have in common a compelling target expression profile with a low risk of on-target/off-tumor toxicity. As such, drug modalities with enhanced effector function, e.g. antibody-drug conjugates, T cell- and NK-cell redirecting antibodies and chimeric antigen receptor (CAR) T-cells, can be employed for generation and development of novel drug candidates.

Furthermore, preclinical and preliminary clinical study results indicate a high probability of efficacy and low safety risk. And, the competitive pipeline for each target has not yet advanced too far and allows new entrants into the race good chances for success.

These four targets are covered by the reports:

• Claudin-6;
• Cadherin-17;
• ROR1;

The reports describe and analyze the target expression profile, provide preclinical and clinical efficacy and safety data; describe potential indications and the respective paptient population, assess the competitive landscape; provide specific profiles of drug candidates in R&D and specific profiles of industry stakeholders.

The reports were prepared in May and June of 2022. The bundle of four reports is available with a 30% discount on list prices.

Claudin 6: A target opportunity to develop effector-enhanced drug modalities

Claudin 6 (CLDN6) is a compelling tumor antigen. The tetraspan membrane protein is a member of the claudin family of tight junction proteins. CLDN6 is an oncofetal tight junction molecule that is expressed during embryonic and fetal development, transcriptionally silenced in adult tissues, and re-expressed on the surface of several epithelial cancers. The transmembrane protein CLDN6 is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need.

Despite being an attractive target due to its exceptionally cancer cell selective expression, therapeutic monoclonal antibodies targeting CLDN6 are difficult to discover due to an abundance of closely related family members and an absolute need for high specificity. Many proteins in the claudin family have high sequence identity. Most similar to CLDN6 is CLDN9, and the two proteins differ at only three of 76 residues in their extracellular loops, creating a challenge for the development of highly selective CLDN6 antibodies.

This report describes and analyzes as of May 2022

• The scientific rationale for CLDN6-targeted therapies based on target characteristics and its differential expression profile;

• Preclinical proof-of-concept of CLDN6-targeted different drug modalities;

• Clinical experience with CLDN6-targeted therapies;

• Clinical indications suitable for development of CLDN6-targeted therapies and their patient populations;

• The competitive landscape of CLDN6-targeted drug modalities in development;

• Specific profiles of CLDN6-targeted drug modalities; and

• Profiles of companies active in the development of anti-CLDN6 therapy candidates.

Effector-enhanced antibodies and cells such as antibody-drug conjugates, chimeric antigen receptor (CAR) T-cells, and bispecific antibodies redirecting T-cells or specifically activating T-cells will be enabled by and benefit from the cancer selective expression profile and the high target selectivity to avoid on-target, off-tumor toxicity.

Despite the technical challenge, novel cellular and humoral CLDN6-targeted drug modalities have emerged and the first product candidates entered clinical development. The facts that preliminary clinical experience shows high anti-tumor activity of the first drug candidate and that the competitive field still is limited, make claudin 6 an exceptionally attractive target for drug discovery and development.

Cadherin 17: A target opportunity to develop effector-enhanced drug modalities

Cadherins are a family of glycoproteins responsible for calcium ion-dependent cell adhesion. There are more than 100 types of cadherins in humans, and many of them are not only responsible for cell adhesion but also involved in tumorigenesis. Cadherin 17 (CDH17), also known as uman liver intestine-cadherin (LI-cadherin), or intestinal human peptide transporter-1 (HPT-1), is a non-classical cadherin composed of an ectodomain consisting of seven extracellular cadherin (EC) repeats, a single transmembrane domain, and a short cytoplasmic domain.

CDH17 is a highly specific marker of gastrointestinal epithelium; most gastrointestinal adenocarcinomas are CDH17-positive with strong membranous staining. However, healthy tissue colonic mucosa and duodenal mucosa also are positive for CDH17 which prevented consideration of CDH17 as an ideal tumor associated antigen for development of CDH17-targeted therapies.

It was only very recently, that investigators discovered that CDH17 is masked in healthy tissue and is not attacked by large molecules or cells. Thus, CDH17 represents a class of previously unappreciated tumor-associated antigens that is 'masked' in healthy tissues from attack by CAR T cells for developing safer cancer immunotherapy.

This report describes and analyzes as of May 2022

• The scientific rationale for CDH17-targeted therapies based on target characteristics and its differential expression profile;

• Preclinical proof-of-concept of CDH17-targeted different drug modalities;

• Clinical indications suitable for development of CDH17-targeted therapies and their patient populations;

• The competitive landscape of CDH17-targeted drug modalities in development;

• Specific profiles of CDH17-targeted drug modalities; and

• Profiles of companies active in the development of anti-CDH17 therapy candidates.

Effector-enhanced antibodies and cells such as antibody-drug conjugates, chimeric antigen receptor (CAR) T-cells, and bispecific antibodies redirecting T-cells or specifically activating T-cells will be enabled by and benefit from the cancer "selective" expression profile to avoid on-target, off-tumor toxicity.

CDH17 provides a great opportunity for drug discovery and development as the competitive landscape still is very favorable for new entrants, but the first molecules have entered clinical development.

ROR1-Targeted Therapy: Target Expression Profile, Safety & Efficacy of Drug Modalities, Pipeline Review, and Competitive Landscape Analysis

This report evaluates Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) from an industry perspective for its suitability as a tumor-specific target for cancer therapy based on its expression profile and preclinical and clinical safety and efficacy data of the various drug modalities employed for discovery and development of ROR1-targeted therapy candidates.

The report has identified the players in the field and presents a competitive landscape analysis of stakeholders and a pipeline review based on the specific profiles of drug candidates and companies active in the field. The report includes information about business transaction in the field, such as acquisitions, partnerships & collaborations and licensing deals. Furthermore, the financial background and situation of the key players is described.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type I transmembrane protein that is physiologically expressed in early embryogenesis and plays a critical role in organogenesis. Expression of ROR1 attenuates rapidly after embryonic development, becoming virtually undetectable on post-partem tissues, with the exception of a few B cell precursors. In contrast, ROR1 is expressed on a variety of cancers, particularly those that are less differentiated, and is associated with early relapse after therapy or metastasis.

Because of its tumor-specific expression and potential functional significance, ROR1 has become of interest as a target for various drug modalities, especially with enhanced effector function. The most advanced molecules is currently being evaluated in potentially registrational phase II/III studies, but the majority of programs are in late preclinical and early clinical development, thus still offering opportunities for improvements.

This report is based information retrieved from proprietary database, clinical trial registries, abstracts, presentations and posters from scientific meetings as well as full publications, from company websites, press releases, SEC filings, investor and R&D presentations. The report was prepared in May/June of 2022 and was released on June 16, 2022.

What will you find in the report:

• The scientific rationale for ROR1-targeted therapies based on target characteristics and its differential expression profile;

• Preclinical safety of ROR1-targeted therapy candidates;

• Clinical experience and proof-of-concept with ROR1-targeted drug modalities;

• Clinical indications suitable for development of ROR1-targeted therapies and their patient populations;

• The competitive landscape of ROR1-targeted drug modalities in development;

• Specific profiles of ROR1-targeted drug modalities; and

• Profiles of companies active in the development of anti-ROR1 therapy candidates.

GPRC5D-Targeted Therapy: Target Expression Profile, Safety & Efficacy of Drug Modalities, Pipeline Review, and Competitive Landscape Analysis

This report evaluates G-protein-coupled receptor family C group 5 member D (GPRC5D) from an industry perspective for its suitability as a tumor-specific target for cancer therapy based on its expression profile and preclinical and clinical safety and efficacy data of the various drug modalities employed for discovery and development of GPRC5D-targeted therapy candidates.

The report has identified the players in the field and presents a competitive landscape analysis of stakeholders and a pipeline review based on the specific profiles of drug candidates and companies active in the field. The report includes information about business transactions in the field, such as acquisitions, partnerships & collaborations and licensing deals. Furthermore, the financial background and situation of the key players is described.

GPRC5D is a type C seven-pass transmembrane protein. The endogenous ligands and signaling mechanism, and thereby, its physiological function and its role in cancer remain unknown. GPRC5D is expressed on malignant bone marrow plasma cells, whereas normal tissue expression is limited to skin (hair follicles and eccrine glands) and the testis (seminiferous tubules). The restricted GPRC5D expression profile indicates that the potential for undesired on target/off tumor effects is small. GPRC5D expression on CD138 cells is independent of B-cell maturation antigen (BCMA) expression and showed a membranous pattern.

Treatment of multiple myeloma with BCMA-targeted drug modalities induces high overall response rates. However, relapse occurs commonly. A reservoir of multiple myeloma cells lacking sufficient BCMA surface expression (antigen escape) may be implicated in relapse. Thus, targeting BCMA may be an efficient therapeutic strategy for BCMA treatment- refractory or -relapsed multiple myeloma patients to address BCMA escape and potentially confer cure.

This report is based information retrieved from proprietary database, clinical trial registries, abstracts, presentations and posters from scientific meetings as well as full publications, from company websites, press releases, SEC filings, investor and R&D presentations. The report was prepared in June of 2022 and was released on July 1, 2022.

What will you find in the report:

• The scientific rationale for GPRC5D-targeted therapies based on target characteristics and its differential expression profile;

• Preclinical efficacy and safety of GPRC5D-targeted therapy candidates;

• Clinical efficacy and safety of GPRC5D-targeted drug modalities;

• Patient population for GPRC5D-targeted therapies;

• The competitive landscape of GPRC5D-targeted drug modalities in R&D;

• Specific profiles of GPRC5D-targeted drug modalities; and

• Profiles of companies active in the development of anti-GPRC5D therapy candidates.

Table of Contents

Claudin 6: A target opportunity to develop effector-enhanced drug modalities

1. Target Background

2. Target Antigen Expression Profile

3. Preclinical Proof-of-Concept

4. Clinical Experience with CLDN6-Targeted Drug Modalities

5. Clinical Indications & Patient Populations

6. Competitive Landscape & Drug Modalities

7. Drug & Cell Therapy Candidate Profiles

• 7.1. CAR T-Cells
• 7.2. Antibody-Drug Conjugates (ADC)
• 7.3. T-Cell Redirecting Bispecific Antibodies
• 7.4. T-Cell Activating Bispecific Antibodies
• 7.5. Failed Drug Modalities

8. Company Profiles

9. References

Cadherin 17: A target opportunity to develop effector-enhanced drug modalities

1. Target Background

2. Target Antigen Expression Profile

3. Preclinical Proof-of-Concept

4. Clinical Indications & Patient Populations

5. Competitive Landscape & Drug Modalities

6. Drug & Cell Therapy Candidate Profiles

• 6.1. CAR T-Cells
• 6.2. Pro-Apoptotic Bispecific Antibodies
• 6.3. T-Cell Redirecting Bispecific Antibodies
• 6.4. Naked Antibodies

7. Company Profiles

8. References

ROR1-Targeted Therapy: Target Expression Profile, Safety & Efficacy of Drug Modalities, Pipeline Review, and Competitive Landscape

0. Executive Summary

1. Target Background: Structure & Function

2. Target Antigen Expression Profile

• 2.1. Hematologic Malignancies
• 2.2. Various Solid Tumors
• 2.3. Lung Cancer
• 2.4. Pancreatic Cancer
• 2.5. Colorectal Cancer
• 2.6. Breast Cancer
• 2.7. Ovarian Cancer

3. Preclinical Safety of ROR1-Targeted Therapy Candidates

4. Clinical Experience with ROR1-Targeted Drug Modalities

5. Clinical Indications & Patient Populations

• 5.1. Chronic Lymphocytic Leukemia
• 5.2. Mantle Cell Lymphoma
• 5.3. Diffuse Large B-Cell Lymphoma
• 5.4. Triple Negative Breast Cancer

6. Competitive Landscape & Drug Modalities

• 6.1. ROR1-Targeted Antibody Drug Conjugates
• 6.2. T-Cell EngagingAnti-ROR1 Antibodies
• 6.3. Adoptive Cell Therapy with ROR1-Targeted CAR T-Cells and NK Cells
• 6.4. ROR1 Small Molecule Inhibitor

7. Drug & Cell Therapy Candidate Profiles

• 7.1. Naked Antibody
• 7.2. Antibody-Drug Conjugates
• 7.3. T-Cell Engaging Bispecific Antibodies
• 7.4. CAR T-Cells & NK Cells
• 7.5. Small Molecule Inhibitor

8. Company Profiles

9. References

GPRC5D-Targeted Therapy: Target Expression Profile, Safety & Efficacy of Drug Modalities, Pipeline Review, and Competitive Landscape Analysis

1. GPRC5D mRNA and Protein Expression Profile

2. Preclinical Efficacy and Safety

3. Clinical Efficacy and Safety of GPRC5D-Targeted Drug Modalities

4. Target Patient Populations

5. Competitive Landscape & Drug Modalities

6. Antibody & Cell Therapy Candidate Profiles

• 6.1. Antibody-Based Drug Modalities
• 6.2. Cell-Based Drug Modalities

7. Company Profiles

8. References