PRMT5 标靶疗法的全球市场和临床试验机会展望:2024 年

PRMT5（蛋白质精氨酸甲基转移□5）是细胞内具有多种功能的重要酵素。PRMT5 通常催化组蛋白的对称和不对称二甲基化，并在翻译后修饰中发挥重要作用。然而，过去二十年进行的研究表明，PRMT5 失调会促进多种疾病进程，使其成为有吸引力的治疗标靶。儘管 PRMT5 标靶治疗市场仍处于早期阶段，并且由于有前景的候选药物停产而遭受了一些挫折，但当前的市场状况表明 PRMT5 标靶疗法有潜力成为多种治疗方案的重要组成部分。疾病，它指向某个未来。

PRMT5 的初步研究集中在癌症上，发现 PRMT5 甲基化属于不同蛋白质亚类的众多底物，从而产生多种促癌作用。例如，当 PRMT5 甲基化转录调节因子 E2F1 时，其半衰期会缩短，这表明大肠直肠癌具有致癌潜力。同样，DNA 损伤反应蛋白 TDP1 的甲基化会增加其活性并防止癌细胞死亡。PRMT5 介导的剪接蛋白 SRSF1 甲基化也与急性骨髓性白血病的致癌活性有关。因此，抑制 PRMT5 对实体癌和血液癌均具有广泛的抗癌作用。

除了癌症之外，PRMT5 还与自体免疫疾病和发炎性疾病有关，其中 PRMT5 透过很大程度上未知的途径触发异常的免疫反应和发炎。PRMT5 透过 NF-kB 途径促进 CD4+ T 细胞发育，并增加 IL-2 的产生和增殖。此外，PRMT5 水平在记忆 Th 细胞增殖高峰期间升高。同样，在微生物感染，尤其是病毒感染中，PRMT5 参与病原体存活以及抗病毒和抗菌反应。越来越多的检查 PRMT5 治疗效果的临床研究表明，这一领域的研究尚未充分，但有可能使用 PRMT5 抑制剂进行治疗。

几种小分子 PRMT5 抑制剂目前正在进行研究和临床试验。2015年Epizyme和GSK共同开发的EPZ015666标誌着PRMT5标靶药物领域的分水岭时刻。EPZ015666 是第一个 PRMT5 小分子化学抑制剂，其选择性比其他 20 种蛋白质甲基转移□高 20,000 倍以上。两家公司也开发了 EPZ015938，这是 EPZ015666 的类似产品，但由于策略考虑，这两个项目都被放弃了。儘管如此，两家公司都创建了一个框架，将 PRMT5 作为抗癌药物的治疗靶点，并证明了小分子抑制剂限制 PRMT5 作用的潜力。

AMG 193、AZD3470、TNG462 和 SCR-6920 等下一代抑制剂透过优化与 PRMT5 上特定位点的相互作用，显示出更高的特异性。这些在异种移植模型中显示出肿瘤生长抑製作用。此外，鑑于 PRMT5 在癌症以外的多种疾病中具有基于背景的功能，蛋白水解靶向嵌合体 (PROTAC) 技术和 PRMT5 活化剂也提供了替代的靶向方法。

为了增强PRMT5抑制的有效性，临床前和临床研究中不仅考虑单一疗法，还考虑合併疗法。PRMT5 和 BCL-2 的双重抑制已显示出比单一疗法增强治疗效果的潜力。这种组合旨在克服限制单一药物治疗功效的补偿性生存讯号。Amgen company也正在评估 PRMT5 抑制剂 AMG193 与现有化疗药物多西紫杉醇的组合。

本报告考察了全球 PRMT5 标靶治疗市场，概述了 PRMT5 标靶治疗的历史和演变，以及临床试验机会、按适应症和地区划分的趋势以及进入市场的公司概况。

目录

第一章 PRMT5标靶治疗简介

• 概述
• DLL3标靶治疗的历史与演变

第二章 PRMT5 标靶治疗方法

• 小分子抑制剂
• 蛋白水解剂
• 小分子活化剂

第 3 章 PRMT5 标靶治疗的功能（依适应症）

• 癌症
• 自体免疫疾病与发炎性疾病
• 心血管疾病
• 微生物感染

第四章 全球PRMT5标靶治疗临床试验概述

• 按公司
• 按指示
• 按地点
• 按患者细分
• 相别

第五章 全球 PRMT5 标靶疗法的临床试验（依公司、适应症和阶段）

• 研究
• 临床前
• 第一阶段
• 一期/二期
• 第二阶段

第六章 PRMT5标靶治疗及区域市场趋势研究

• 美国
• 英国
• 欧洲联盟
• 中国
• 加拿大

第七章 PRMT5标靶治疗市场趋势及临床试验展望

• 当前市场趋势、发展和临床试验的评估
• 未来商业化的可能性

第八章 PRMT5标靶治疗市场动态

• 驱动因素和机遇
• 挑战和限制因素

第9章 竞争格局

• Abbisko Therapeutics
• Agios Pharmaceuticals
• Amgen
• AstraZeneca
• Aurigene Oncology
• CytosinLab Therapeutics
• Epizyme (Ipsen)
• IngenOx Therapeutics
• Johnson & Johnson
• Jubilant Therapeutics
• Mirati Therapeutics
• Ryvu Therapeutics
• Schrodinger
• Simcere Pharmaceutical Group
• SK Life Science
• Tango Therapeutics

“Global PRMT5 Targeted Therapy Market & Clinical Trials Opportunity Outlook 2024 ” Report Highlights:

• PRMT5 Targeted Therapies Clinical Trials By Company, Indication & Phase
• PRMT5 Targeted Therapies In Clinical Trials: > 25
• PRMT5 Targeted Therapies Research & Market Trends by Region: US, UK, EU, China & Canada
• Current Market Trends, Developments & Clinical Trials Assessment
• PRMT5 Targeted Therapy Approaches
• Application Of PRMT5 Targeted Therapies by Indication

PRMT5, or Protein Arginine Methyltransferase 5, is an important enzyme with a variety of functions in cells. PRMT5 normally catalyzes the symmetrical and asymmetrical dimethylation of histone proteins, which plays an important role in post translational modifications. However, research studies conducted over the last two decades have revealed that its dysregulation promotes various disease processes, making it an attractive therapeutic target. Though the PRMT5 targeted therapies market is still in its early stages, with setbacks caused by the discontinuation of promising candidates, the current market landscape points to a future in which PRMT5 targeted therapies may become essential components of various treatment regimens for a wide range of diseases.

The initial research efforts for PRMT5 were focused on cancer, where it was discovered that PRMT5 methylates numerous of its substrates, which belong to diverse protein subclasses, resulting in varying pro-cancer effects. For example, PRMT5's methylation of the transcription regulator E2F1 shortens its half-life, which has oncogenic implications in colon cancer. Similarly, methylation of TDP1, a DNA damage response protein, increases its activity, hence preventing cancer cell death. PRMT5-mediated methylation of SRSF1, a splicing protein, has also been linked to carcinogenic activities in acute myeloid leukemia. As a result, inhibiting PRMT5 has a wide anticancer effect on both solid and hematological malignancies.

Beyond cancer, PRMT5 is linked in autoimmune and inflammatory diseases, where PRMT5 causes abnormal immune responses and inflammations via largely unknown pathways. PRMT5 promotes CD4+ T cell development via the NF-κB pathway, leading to elevated IL-2 production and proliferation. Furthermore, PRMT5 levels were elevated during the height of memory Th cell proliferation. Similarly, in microbial infections, particularly viral infections, PRMT5 has been linked to pathogen survival as well as antiviral and antibacterial responses. Again, this area is under-researched, but it has the potential to be treated with PRMT5 inhibitors, according to an increasing body of clinical investigations looking into the therapeutic benefits of PRMT5.

Multiple small-molecule PRMT5 inhibitors are now under research and clinical testing. The development of EPZ015666 by Epizyme and GSK in 2015 was a watershed moment in the field of PRMT5-targeted medicines. EPZ015666 was the first small chemical inhibitor of PRMT5 with over 20000-fold selectivity over 20 other protein methyltransferases. The two companies also developed EPZ015938, an analog of EPZ015666, but both programs were abandoned due to strategic considerations. Nonetheless, they laid the framework for establishing PRMT5 as a therapeutic target for anticancer therapies, as well as the potential of small molecule inhibitors to limit PRMT5 actions, both of which are still being widely investigated in research.

Next-generation inhibitors like AMG 193, AZD3470, TNG462 and SCR-6920 demonstrate improved specificity by optimizing interactions with particular sites on PRMT5. These have shown tumor growth inhibition in xenograft models. In addition, proteolysis targeting chimeras (PROTACs) technology and PRMT5 activators also offer alternative targeting approaches, considering PRMT5 has context-based functions in several diseases outside cancer.

Beyond monotherapies, combination strategies are also being explored in preclinical and clinical trials to enhance PRMT5 inhibition efficacy. Dual inhibition of PRMT5 and BCL-2 has shown potential for enhanced therapeutic effects, better than what was seen by the therapies alone. Such combinations aim to overcome compensatory survival signaling that can limit the therapeutic benefits of single agents. Amgen is also assessing the combination of its PRMT5 inhibitor AMG 193 in combination with the established chemotherapy drug, Docetaxel.

Regulatory bodies such as the FDA have also aided the development of PRMT5-targeted therapies by granting them designations, allowing their developers to obtain certain benefits. For example, in February 2023, the FDA designated JBI-778, a highly differentiated, substrate competitive PRMT5 inhibitor being developed by Jubilant Therapeutics, as an orphan drug for the treatment of Glioblastoma Multiforme. JBI-778 is being developed as an oral, brain-penetrant PRMT5 inhibitor for the treatment of both brain metastases and primary brain cancers. The Orphan Drug Designation grants tax breaks and market exclusivity upon approval, which can assist JBI-778 establish itself as a preferred therapy after marketing approval.

Commercially, targeting PRMT5 in order to inhibit or activate its functions represents a novel and viable strategy; however, this entirely depends on clinical benefits demonstrated in preclinical and clinical trials in specific indications. Given the potential broad applicability of PRMT5-targeting therapies, the first-in-class therapeutic to target PRMT5 may achieve high sales. Combination therapies could further expand market size. However, realizing the full clinical and commercial potential will require validating efficacy and defining suitable patient populations through biomarker-guided trials.

Table of Contents

1. Introduction to PRMT5 Targeted Therapy

• 1.1. Overview
• 1.2. History & Evolution of PRMT5 Targeted Therapy

2. PRMT5 Targeted Therapy Approaches

• 2.1. Small Molecule Inhibitors
• 2.2. Protein Degraders
• 2.3. Small Molecule Activators

3. Role of PRMT5 Targeted Therapies by Indication

• 3.1. Cancers
  • 3.1.1. Solid Cancers
  • 3.1.2. Hematological Cancers
• 3.2. Autoimmune & Inflammatory Diseases
• 3.3. Cardiovascular Diseases
• 3.4. Microbial Infections

4. Global PRMT5 Targeted Therapies Clinical Trials Overview

• 4.1. By Company
• 4.2. By Indication
• 4.3. By Location
• 4.4. By Patient Segment
• 4.5. By Phase

5. Global PRMT5 Targeted Therapies Clinical Trials By Company, Indication & Phase

• 5.1. Research
• 5.2. Preclinical
• 5.3. Phase-I
• 5.4. Phase-I/II
• 5.5. Phase-II

6. PRMT5 Targeted Therapies Research & Market Trends by Region

• 6.1. US
• 6.2. UK
• 6.3. EU
• 6.4. China
• 6.5. Canada

7. PRMT5 Targeted Therapies Market Trends & Clinical Trials Outlook

• 7.1. Current Market Trends, Developments & Clinical Trials Assessment
• 7.2. Future Commercialization Opportunity

8. PRMT5 Targeted Therapies Market Dynamics

• 8.1. Drivers & Opportunities
• 8.2. Challenges & Restraints

9. Competitive Landscape

• 9.1. Abbisko Therapeutics
• 9.2. Agios Pharmaceuticals
• 9.3. Amgen
• 9.4. AstraZeneca
• 9.5. Aurigene Oncology
• 9.6. CytosinLab Therapeutics
• 9.7. Epizyme (Ipsen)
• 9.8. IngenOx Therapeutics
• 9.9. Johnson & Johnson
• 9.10. Jubilant Therapeutics
• 9.11. Mirati Therapeutics
• 9.12. Ryvu Therapeutics
• 9.13. Schrodinger
• 9.14. Simcere Pharmaceutical Group
• 9.15. SK Life Science
• 9.16. Tango Therapeutics

List of Figures

• Figure 1-1: PRMT5 - Normal Functions
• Figure 1-2: PRMT5 - Oncogenic Functions
• Figure 1-3: PRMT5 - Important Milestones in Development
• Figure 2-1: PRMT5 - Binding Sites for Small Molecule Inhibitors
• Figure 2-2: PROTACs - Mechanism of Action
• Figure 2-3: PROTACs - Advantages
• Figure 3-1: PRMT5 - Roles in Solid Cancers
• Figure 3-2: PRMT5 - Roles in Hematological Cancers
• Figure 3-3: PRMT5 - Roles in Diabetes
• Figure 3-4: PRMT5 - Roles in Microbial Infections
• Figure 4-1: Global - PRMT5 Targeted Therapies Clinical Trials By Company (Number), 2024
• Figure 4-2: Global - PRMT5 Targeted Therapies Clinical Trials By Indication (Number), 2024
• Figure 4-3: Global - PRMT5 Targeted Therapies Clinical Trials By Location (Number), 2024
• Figure 4-4: Global - PRMT5 Targeted Therapies Clinical Trials By Patient Segment (Number), 2024
• Figure 4-5: Global - PRMT5 Targeted Therapies Clinical Trials By Phase (Number), 2024
• Figure 6-1: NCT05094336 Phase 1/2 Study - Initiation & Completion Year
• Figure 6-2: NCT05528055 Phase 1 Study - Initiation & Completion Year
• Figure 8 1: PRMT5 Targeted Therapies Market - Drivers & Opportunities
• Figure 8 2: PRMT5 Targeted Therapies Market - Challenges & Restraints

List of Tables

• Table 6-1: US - Ongoing Studies for PRMT5 Inhibitors
• Table 6-2: UK - Ongoing Studies for PRMT5 Inhibitors
• Table 6-3: EU - Ongoing Studies for PRMT5 Inhibitors
• Table 6-4: China - Ongoing Studies for PRMT5 Inhibitors
• Table 6-5: Canada - Ongoing Studies For PRMT5 Inhibitors