RNA聚合酵素I的全球市场:临床试验，各适应症开发趋势，标的方法，市场机会(2025年)

"全球 RNA 聚合酶 I 市场：临床试验、各适应症发展趋势、标靶治疗方案、市场机会 (2025)" 报告重点与发现

• 研究方法
• 针对 RNA 聚合酶 I 的临床方法
• RNA 聚合酶 I 抑制剂及其各适应症的临床趋势
• RNA 聚合酶 I 抑制剂临床试验洞察：按公司、国家、适应症和阶段划分
• 当前市场情势与未来机遇
• 竞争格局

RNA 聚合酶 I 抑制剂的需求及报告意义

由于满足尚未满足的临床需求，标靶治疗依赖核醣体生物合成的癌症，尤其是那些伴随MYC过度表现、同源重组缺陷(HRD)和p53路径改变的癌症。 Pol I催化核醣体RNA (rRNA)的转录，是核醣体生物合成的关键步骤，但在大多数癌症中过度活跃，使其快速生长。这种对核醣体生物合成的癌症特异性依赖性为RNA Pol I抑制剂的标靶治疗提供了机会。与许多标靶讯号通路或DNA复製的疗法不同，Pol I抑制剂透过阻断细胞内的基本过程——蛋白质合成——构成了一种新颖的治疗策略。

在本报告中，我们特别关注直接的RNA聚合酶I抑制剂。虽然已经提到了直接和间接抑制RNA聚合酶I的方法，但我们仅详细介绍了直接靶向RNA聚合酶I的候选药物。我们也谈到了多药理学的概念，但本报告仅涵盖了对RNA聚合酶I具有主要和选择性作用的化合物。

本报告旨在记录最新的科学进展，规划临床管线的进展，并为对这一高风险、高回报肿瘤学领域感兴趣的投资者重点介绍未来的商业和临床前景。

本报告包含临床试验见解

临床上最先进的RNA聚合酶I (Pol I) 抑制剂是pindonarlex (CX-5461)，最初由Peter MacCallum癌症中心开发。 Pindonarlex选择性抑制核醣体DNA (rDNA) 转录并稳定G-四链体结构，从而产生复製压力并激活DNA损伤反应。该药物已在多种癌症类型的临床试验中展现出概念验证疗效，在TP53野生型和突变型肿瘤中均表现出抗肿瘤活性，且安全性可控。基于这些令人鼓舞的结果，FDA已授予其特殊监管资格，以加快其开发。

本报告纳入这些见解，提供了重要的学术和商业更新。

参与RNA聚合酶I抑制剂研发的关键公司

RNA聚合酶I (Pol I)抑制剂市场仍处于早期阶段，少数策略公司和学术机构引领市场发展。 CX-5461仍然是领先的候选药物，最初由Peter MacCallum癌症中心开发，目前由Senhwa Biosciences与德克萨斯大学MD安德森癌症中心等领先机构合作开发。儘管迄今尚未有RNA聚合酶I抑制剂获批，但竞争格局正在逐渐形成。研究也正在扩展到邻近领域，例如其他核醣体生物合成抑制剂和天然产物（如森培韦林），它们能够提供非遗传毒性的聚合酶 I 抑制机制。

报告展示了 RNA 聚合酶 I 抑制剂领域的未来发展方向

RNA 聚合酶 I 抑制剂的前景光明，但这取决于能否克服关键的研发障碍。毒性，尤其是 Pindnarulex 试验中发现的光毒性，仍然是一个剂量限制因素。利用生物标记辅助病患选择也是当务之急。 HRD 状态、MYC 扩增和 rDNA 拷贝数变异目前正在评估中，但尚未被确立为常规临床使用的生物标记。然而，具有更佳毒性特征和序贯给药方案的新型候选药物，例如 PMR-116，有可能解决这些问题。在未来的发展中，POL i 抑制剂与 PARP 抑制剂、拓朴异构酶抑制剂或免疫疗法的联合方案可能有效利用合成致死率并规避抗药性。

本报告强调了以生物标记为导向的策略、个体化给药方案和转化试验设计的必要性，以最大限度地发挥 Pol I 抑制的治疗效益，不仅在实体瘤中，而且在血液系统恶性肿瘤中。

目录

第1章 调查手法

第2章 RNA聚合酵素I的简介

• RNA聚合酵素I的概要与生物学的作用
• 肿瘤形成的核仁压力和核糖体生物合成的重要性

第3章 RNA聚合酵素I为目标的机制的基础

• 标靶RNA聚合酶I的原理
• RNA聚合酶I的直接抑制与间接调控

第4章 RNA聚合酵素I为目标的方法

• 低分子抑制剂
• 多剂联合治疗

第5章 成为RNA聚合酵素I阻碍的对象的疾病领域

• 肿瘤学
  • 造血恶性肿瘤
  • 固态肿瘤
• 新的适应症

第6章 RNA聚合酵素I抑制剂的临床试验:企业，国家，适应症，各相

• 研究
• 第一阶段
• 第二阶段

第7章 RNA聚合酵素I抑制剂的全球市场概要

• 目前市场情势
• 未来的研究开发与商业机会

第8章 RNA聚合酵素I抑制剂市场动态

• 促进因素和机会
• 课题与阻碍因素

第9章 竞争情形

• Pimera
• Senhwa Biosciences

Global RNA Polymerase I Clinical Trials, Development Trends By Indications, Target Approaches & Market Opportunity Insight 2025 Report Highlights & Findings:

• Research Methodology
• Clinical Approaches To Target RNA Polymerase I
• RNA Polymerase I Inhibition & Clinical Trends By Indication
• RNA Polymerase I Inhibitors Clinical Trials Insight By Company, Country, Indication & Phase
• Current Market Scenario & Future Opportunities
• Competitive Landscape

Need For RNA Pol I Inhibitors & Why This Report?

There is a need for RNA Polymerase I (Pol I) inhibitors due to the unmet clinical demand to target ribosome biogenesis-dependent cancers, particularly those with MYC overexpression, homologous recombination deficiencies (HRD), or p53 pathway alterations. Pol I catalyzes the transcription of ribosomal RNA (rRNA), a critical step in ribosome biogenesis, that is overactivated in the majority of cancers to allow for rapid growth. This cancer-specific dependence on ribosome biogenesis offers a window of opportunity RNA Pol I inhibitors seek to target. In contrast to most therapies, which target signaling pathways or DNA replication, Pol I inhibitors constitute a new strategy by blocking the basic cellular process of protein synthesis.

This report focuses specifically on direct RNA polymerase I inhibitors. Although both direct and indirect methods of RNA Pol I inhibition are mentioned, only the candidates that directly target RNA Pol I have been described in detail. We have also touched upon the idea of polypharmacology; however, only those compounds with a primary and selective effect on RNA Pol I are included in this report.

The purpose for this report is to record the latest scientific advancements, plot clinical pipeline progress, and emphasize future commercial and clinical prospects for investors interested in this high-risk, high-reward oncology space.

Clinical Trials Insight Included In Report

The most clinically advanced RNA Polymerase I (Pol I) inhibitor is Pindnarulex (CX-5461), originally developed at the Peter MacCallum Cancer Centre. Pindnarulex works by selectively inhibiting ribosomal DNA (rDNA) transcription and stabilizing G-quadruplex structures, leading to replication stress and activation of the DNA damage response. It has shown proof-of-concept efficacy in clinical trials across multiple cancer types, demonstrating antitumor activity in both TP53 wild-type and mutant tumors, along with a manageable safety profile. Based on these encouraging results, the FDA has granted special regulatory designations to help accelerate its development.

The incorporation of these insights within the report offers a vital update to both academic and commercial audiences.

Key Companies Involved In R&D Of RNA Pol I Inhibitors

The RNA Polymerase I (Pol I) inhibitor market is still in its early stages, with development led by a small number of strategic companies and academic institutions. CX-5461 remains the leading candidate; originally developed at the Peter MacCallum Cancer Centre, it is now being advanced by Senhwa Biosciences in collaboration with major institutions, including the University of Texas MD Anderson Cancer Center. Although no RNA Pol I inhibitor has received regulatory approval to date, the competitive landscape is gradually forming. Research is also expanding into adjacent areas, such as other ribosome biogenesis disruptors and natural products like sempervirine, which offer non-genotoxic mechanisms of Pol I inhibition.

Report Highlighting Future Direction Of RNA Pol I Inhibitors Segment

The future of RNA Pol I inhibitors is bright, but it depends on surmounting decisive development hurdles. Toxicity, especially phototoxicity noted in Pindnarulex trials, continues to be a dose-limiting factor. The requirement of usable biomarkers that can inform patient selection is also a priority. While HRD status, MYC amplification, and rDNA copy number changes are currently being evaluated, they are not yet established as usable for routine clinical practice. Newer candidates such as PMR-116 with purer toxicity profiles and the ability for continuous dosing, however, hold promise for meeting these issues. Future development is likely to benefit combination regimens, like Pol I inhibitors with PARP inhibitors, topoisomerase inhibitors, or even immunotherapies, to take advantage of synthetic lethality and bypass resistance.

This report highlights the need for biomarker-directed strategies, individualized dosing schedules, and translational trial designs to realize the full therapeutic benefits of Pol I inhibition in hematologic malignancies as well as in solid tumors.

Table of Contents

1. RESEARCH METHODOLOGY

2. Introduction To RNA Polymerase I

• 2.1 Brief Overview Of RNA Polymerase I & Biological Role
• 2.2 Importance Of Nucleolar Stress & Ribosomal Biogenesis In Oncogenesis

3. Mechanistic Basis For Targeting RNA Polymerase I

• 3.1 Rationale For Targeting RNA Pol I
• 3.2 Direct Pol I Inhibition vs Indirect Modulation

4. Approaches To Target RNA Polymerase I

• 4.1 Small Molecule Inhibitors
• 4.2 Polypharmacology

5. Disease Areas Of Interest For RNA Polymerase I Inhibition

• 5.1 Oncology
  • 5.1.1 Hematological Malignancies
  • 5.1.2 Solid Tumors
• 5.2 Emerging Indications

6. RNA Polymerase I Inhibitors Clinical Trials Insight By Company, Country, Indication & Phase

• 6.1 Research
• 6.2 Phase I
• 6.3 Phase II

7. Global RNA Polymerase I Inhibitors Market Overview

• 7.1 Current Market Scenario
• 7.2 Future R&D & Commercial Opportunities

8. RNA Polymerase I Inhibitors Market Dynamics

• 8.1 Drivers & Opportunities
• 8.2 Challenges & Restraints

9. Competitive Landscape

• 9.1 Pimera
• 9.2 Senhwa Biosciences

List of Figures

• Figure 2-1: RNA Pol I Transcription & rRNA Processing Pathway
• Figure 2-2: Regulation of RNA Pol I Transcription
• Figure 2-3: RNA Pol I Activity During Cell Cycle
• Figure 2-4: Nucleolar Stress & p53 Activation
• Figure 2-5: Pol I - Therapeutic Inhibition in Cancer
• Figure 2-6: CX-5461 & BMH-21 - Mechanisms Of Action
• Figure 2-7: Nucleolus - Functions
• Figure 2-8: Ribosome Biogenesis - Normal vs Cancer Cell
• Figure 2-9: Cancer Addiction To RNA Polymerase I
• Figure 3-1: Cellular Response To Pol I Inhibition
• Figure 3-2: Direct Pol I Inhibition
• Figure 3-3: Indirect Pol I Inhibition
• Figure 3-4: Consequences Of Pol I Transcription Inhibition
• Figure 4-1: Small Molecule Pol I Inhibitors - Advantages
• Figure 4-2: Polypharmacology In Cancer Treatment
• Figure 5-1: Hematological Malignancies - Mechanism Of Action of Pol I Inhibition
• Figure 5-2: NCI-2025-04787 Phase 1/2 (NCT07069699) Study - Initiation & Completion Year
• Figure 5-3: CX-5461-04 Phase 1 (NCT04890613) Study - Initiation & Completion Year
• Figure 5-4: NCI-2024-07701 Phase 1 (NCT06606990) Study - Initiation & Completion Year
• Figure 7-1: Global RNA Polymerase I Inhibitors Market - Future Opportunities
• Figure 8-1: Global RNA Polymerase I Inhibitors Market - Drivers & Opportunities
• Figure 8-2: Global RNA Polymerase I Inhibitors Market - Key Challenges & Strategic Solutions

List of Tables

• Table 3 1: RNA Polymerase I - Direct Inhibition v/s Indirect Modulation
• Table 4 1: Chemotherapeutic Drugs With Polypharmacologic Activity On Pol I
• Table 6 1: RNA Polymerase I Inhibitors In Research Phase