降解抗體偶聯物 (DAC) 的全球市場：從產業角度對利害關係人、技術、管道和聯盟進行狀況分析 (2024)

Degrader-Antibody Conjugates 2024: A Landscape Analysis of Stakeholders, Technologies, Pipeline and Partnering from an Industry Perspective

出版日期: 2024年09月03日 | 出版商:

La Merie Publishing | 英文 174 Pages | 訂單完成後即時交付

價格

簡介目錄

本報告根據截至2024年9月的行業情況，對DAC（降解抗體偶聯物）利益相關者、平台技術、開發/探索管道以及合作項目進行了解釋和分析。新藥DAC融合了現有技術：抗體藥物偶聯物（ADC）和靶向蛋白水解劑，旨在結合兩種技術的優勢並規避其限制。 DAC 將抗體的特異性與難以藥物化的標靶蛋白質降解劑的效率結合起來。 DAC 為 ADC 公司提供了使用新型有效負載來提高療效和治療窗口的機會，也為靶向蛋白降解 (TPD) 公司提供了改善細胞特異性、半衰期和藥物樣特性的機會。

DAC 療法的兩個主要用途是：

細胞內標靶蛋白降解
細胞外標靶蛋白降解

本報告提供以下方面的最新資訊和分析：

該產業的利害關係人基於製藥公司和 TPD 技術公司的 DAC 活動的公司概況；
使用 PROTAC/分子黏合劑進行蛋白?體降解的 DAC 技術，用於細胞內 TPD；
易受細胞內降解的蛋白質；
用於細胞內降解的E3連接?；
DAC 技術使用廣泛作用的降解劑來處理細胞外 TPD；以及
使用溶小體途徑降解劑的DAC技術；
DAC 臨床和非臨床開發管線；
DAC臨床階段概況；
DAC 的藥物發現管道；
DAC 結合技術和結構概念的臨床前證明；
合作夥伴活動（收購、授權、聯合研究）

DAC最初的概念將其定義為化學偶聯的腫瘤靶向抗體和PROTAC（蛋白水解靶向嵌合體）。 PROTAC 是大型異雙功能小分子，其中一部分透過連接子結合細胞內標靶蛋白(PoI)，例如布魯頓酪胺酸激?(BTK)，第二部分將PoI 與泛素結合，它與將蛋白質轉化為E3 連接?結合，導致細胞質內的蛋白?體降解。儘管大多數 DAC 發現計劃都依賴此概念，但使用分子黏合劑代替 PROTAC 的 DAC 也正在接受研究，甚至是第一個進入臨床評估的 DAC。分子黏合劑型小分子可作為黏合劑，增強 E3 連接?與 PoI 的相互作用，導致泛素化和蛋白?體降解。 PROTAC 比黏合劑更容易設計，因為 E3 連接?和 PoI 的結合位點是獨立的。然而，PROTACs一般分子較大，開發難度較高。另一方面，黏合劑通常具有較小的分子並且更類似於藥物。 DAC 的範圍目前正在擴展到細胞外空間，用於降解膜結合蛋白和可溶性蛋白。細胞外標靶蛋白降解涉及雙特異性生物製劑或小分子，它們將膜結合或分泌的（可溶性）PoI 招募到降解機器中。降解透過跨膜 E3 連接?和細胞激素受體發生，或透過膜結合再循環受體將 PoI 轉運至溶小體。

製藥企業
- Bristol Myers Squibb
- CSPC Pharmaceutical Group
- Debiopharm
- Eisai
- GlaxoSmithKline
- Merck KGaA
- Merck & Co. (MSD)
- Novartis
- Pfizer
- Pierre Fabre
- Roche
- Vertex Pharmaceuticals
科技企業
- C4 Therapeutics
- Crossfire Oncology
- Cullgen
- EpiBiologics
- Firefly Bio
- InduPro
- Lycia Therapeutics
- NanoMedSyn
- NIBEC
- Nurix Therapeutics
- Orum Therapeutics
- Prelude Therapeutics
- Ubix Therapeutics
- VectorY Therapeutics

第8章 DAC技術的簡介

AMFA
CELMoD ADC
Degraducer
DELigase
EpiTAC
EPriL
LYTAC & GELYTAC
PROTAB
PROxAb
REULR
TORPEDO
TPD2
uSMITE
VecTron

第9章參考文獻

簡介目錄

Product Code: LMFR0041

This report provides you with a landscape description and analysis of degrader-antibody conjugate (DAC) stakeholders, platform technologies, development and discovery pipelines and partnering deals from an industry perspective as of September 2024. The emerging novel drug modality of degrader-antibody conjugates represents the convergence of the existing technologies of antibody-drug conjugation and targeted protein degradation with the goal of combining the strengths and avoiding the limitations of both technologies. DACs combine the specificity of antibodies with the efficiency of degraders of difficult to drug protein targets. Degrader-antibody conjugates provide plenty of opportunities for ADC companies to use a novel payload to improve efficacy and the therapeutic window and for targeted protein degradation (TPD) companies to improve cell-specificity, half-life and drug-like properties.

The two main uses for Degrader-Antibody Conjugate therapy are:

Intracellular Targeted Protein Degradation
Extracellular Targeted Protein Degradation

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

Stakeholders in the field, by company profiles of DAC activities at pharmaceutical and TPD technology companies;
DAC technologies using PROTAC and molecular glue for proteasomal degradation for intracellular TPD;
Proteins-of-interest for intracellular degradation;
E3 ligases used for intracellular degradation;
DAC technologies using broadly acting degraders for extracellular TPD; and
DAC technologies with lysosomal pathway degraders;
Clinical and non-clinical development pipeline of DACs;
Profiles of clinical stage DACs;
DAC discovery pipeline;
Preclinical proof-of-concept of DAC conjugate technologies and constructs;
Partnering activities (acquisition, licensing, collaborations)

The original concept of degrader-antibody conjugates defines DACs as tumor-targeted antibodies chemically conjugated to proteolysis-targeting chimera (PROTACs). PROTACs are large heterobifunctional small molecules with one part binding to the intracellular protein of interest (PoI), e.g. Brutons Tyrosine Kinase (BTK), via a linker to a second part which binds to an E3 ligase that ubiquitylates the PoI, resulting in proteasomal degradation in the cytosol. The majority of DAC discovery programs rely on this concept, but DAC using a molecular glue instead of a PROTAC are also being pursued and even are the first in clinical evaluation. Molecular glue-type small molecules act as an glue that enhances the interaction between an E3 ligase and a PoI, leading to its ubiquitylation and proteasomal degradation. PROTACs are easier to design than glues given their independent binding sites to the E3 ligase and the PoI. However, they are generally large molecules that can be challenging to develop, whereas glues are typically smaller and more drug-like. The scope of degrader-antibody conjugates is currently being expanded into the extracellular space for degradation of membrane bound and soluble proteins. Extracellular targeted protein degradation involves bispecific biologics or small molecules that recruit the PoI, either membrane-bound or secreted (soluble), to a degradation machinery. Degradation may occur through a transmembrane E3 ligase, or a cytokine receptor or via a membrane bound recycling receptor for transport of the PoI to the lysosome, which is the typical pathway for the degradation of extracellular proteins.

Methodology:

This report evaluates the industry landscape of degrader-antibody conjugation in research and development. The report provides a comprehensive overview of the R&D and partnering activities of pharmaceutical and technology companies in the field of degrader-antibody conjugates. This report is based on the identification and description of 26 corporate stakeholders: 12 pharmaceutical companies and 14 technology companies. All publicly available information is fully referenced, either with scientific references (abstracts, posters, presentations, full paper) or hyperlinks leading to the source of information, such as press releases, corporate presentations, annual reports, SEC disclosures and homepage content.

The report has four analytical chapters about stakeholders, DAC technologies, DAC R&D including pipeline, and DAC partnering. Analysis is based on information presented in the two subsequent chapters with specific profiles of companies and technologies. A list of scientific references is provided in the last chapter of the report followed by an overview of the Tables in the text.

1 Executive Summary

2 Introduction

3 Analysis of Stakeholders in Degrader-Antibody Conjugate R&D

3.1 Pharmaceutical Companies
3.2 Technology Companies

4 Analysis of Degrader-Antibody Conjugate Technologies

4.1 Overview of Degrader-Antibody Conjugate Technologies
4.2 Degrader-Antibody Conjugates with Molecular Glue-type Degraders
4.3 Degrader-Antibody Conjugates with PROTAC-type Degraders
4.4 Degrader-Antibody Conjugates with Broadly Acting Degraders
4.5 Degrader-Antibody Conjugates with Lysosomal Pathway Degraders

5 Analysis of Degrader-Antibody Conjugate Research & Development

5.1 Clinical & Nonclinical Development Pipeline of Degrader-Antibody Conjugates
- 5.1.1 Profile of ORM-6151
- 5.1.2 Profile of ORM-5029
5.2 Pipeline of Discovery Stage Degrader-Antibody Conjugate Programs
5.3 Preclinical Proof-of-Concept of Degrader-Antibody Conjugate Technologies and Constructs

6 Analysis of Partnering in the Field of Degrader-Antibody Conjugate Partnering

6.1 Acquisition
6.2 Licensing
6.3 Discovery Collaborations

7 Profiles of Companies with Degrader-Antibody Conjugate R&D

7.1 Pharmaceutical Companies
- 7.1.1 Bristol Myers Squibb
- 7.1.2 CSPC Pharmaceutical Group
- 7.1.3 Debiopharm
- 7.1.4 Eisai
- 7.1.5 GlaxoSmithKline
- 7.1.6 Merck KGaA
- 7.1.7 Merck & Co. (MSD)
- 7.1.8 Novartis
- 7.1.9 Pfizer
- 7.1.10 Pierre Fabre
- 7.1.11 Roche
- 7.1.12 Vertex Pharmaceuticals
7.2 Technology Companies
- 7.2.1 C4 Therapeutics
- 7.2.2 Crossfire Oncology
- 7.2.3 Cullgen
- 7.2.4 EpiBiologics
- 7.2.5 Firefly Bio
- 7.2.6 InduPro
- 7.2.7 Lycia Therapeutics
- 7.2.8 NanoMedSyn
- 7.2.9 NIBEC
- 7.2.10 Nurix Therapeutics
- 7.2.11 Orum Therapeutics
- 7.2.12 Prelude Therapeutics
- 7.2.13 Ubix Therapeutics
- 7.2.14 VectorY Therapeutics