RNA聚合酵素I的全球市場:臨床試驗，各適應症開發趨勢，標的方法，市場機會(2025年)

"全球 RNA 聚合酶 I 市場：臨床試驗、各適應症發展趨勢、標靶治療方案、市場機會 (2025)" 報告重點與發現

• 研究方法
• 針對 RNA 聚合酶 I 的臨床方法
• RNA 聚合酶 I 抑制劑及其各適應症的臨床趨勢
• RNA 聚合酶 I 抑制劑臨床試驗洞察：按公司、國家、適應症和階段劃分
• 當前市場情勢與未來機遇
• 競爭格局

RNA 聚合酶 I 抑制劑的需求及報告意義

由於滿足尚未滿足的臨床需求，標靶治療依賴核醣體生物合成的癌症，尤其是那些伴隨MYC過度表現、同源重組缺陷(HRD)和p53路徑改變的癌症。 Pol I催化核醣體RNA (rRNA)的轉錄，是核醣體生物合成的關鍵步驟，但在大多數癌症中過度活躍，使其快速生長。這種對核醣體生物合成的癌症特異性依賴性為RNA Pol I抑制劑的標靶治療提供了機會。與許多標靶訊號通路或DNA複製的療法不同，Pol I抑制劑透過阻斷細胞內的基本過程——蛋白質合成——構成了一種新穎的治療策略。

在本報告中，我們特別關注直接的RNA聚合酶I抑制劑。雖然已經提到了直接和間接抑制RNA聚合酶I的方法，但我們僅詳細介紹了直接靶向RNA聚合酶I的候選藥物。我們也談到了多藥理學的概念，但本報告僅涵蓋了對RNA聚合酶I具有主要和選擇性作用的化合物。

本報告旨在記錄最新的科學進展，規劃臨床管線的進展，並為對這一高風險、高回報腫瘤學領域感興趣的投資者重點介紹未來的商業和臨床前景。

本報告包含臨床試驗見解

臨床上最先進的RNA聚合酶I (Pol I) 抑制劑是pindonarlex (CX-5461)，最初由Peter MacCallum癌症中心開發。 Pindonarlex選擇性抑制核醣體DNA (rDNA) 轉錄並穩定G-四鏈體結構，從而產生複製壓力並激活DNA損傷反應。該藥物已在多種癌症類型的臨床試驗中展現出概念驗證療效，在TP53野生型和突變型腫瘤中均表現出抗腫瘤活性，且安全性可控。基於這些令人鼓舞的結果，FDA已授予其特殊監管資格，以加快其開發。

本報告納入這些見解，提供了重要的學術和商業更新。

參與RNA聚合酶I抑制劑研發的關鍵公司

RNA聚合酶I (Pol I)抑制劑市場仍處於早期階段，少數策略公司和學術機構引領市場發展。 CX-5461仍然是領先的候選藥物，最初由Peter MacCallum癌症中心開發，目前由Senhwa Biosciences與德克薩斯大學MD安德森癌症中心等領先機構合作開發。儘管迄今尚未有RNA聚合酶I抑制劑獲批，但競爭格局正在逐漸形成。研究也正在擴展到鄰近領域，例如其他核醣體生物合成抑制劑和天然產物（如森培韋林），它們能夠提供非遺傳毒性的聚合酶 I 抑制機制。

報告展示了 RNA 聚合酶 I 抑制劑領域的未來發展方向

RNA 聚合酶 I 抑制劑的前景光明，但這取決於能否克服關鍵的研發障礙。毒性，尤其是 Pindnarulex 試驗中發現的光毒性，仍然是一個劑量限制因素。利用生物標記輔助病患選擇也是當務之急。 HRD 狀態、MYC 擴增和 rDNA 拷貝數變異目前正在評估中，但尚未被確立為常規臨床使用的生物標記。然而，具有更佳毒性特徵和序貫給藥方案的新型候選藥物，例如 PMR-116，有可能解決這些問題。在未來的發展中，POL i 抑制劑與 PARP 抑制劑、拓樸異構酶抑制劑或免疫療法的聯合方案可能有效利用合成致死率並規避抗藥性。

本報告強調了以生物標記為導向的策略、個體化給藥方案和轉化試驗設計的必要性，以最大限度地發揮 Pol I 抑制的治療效益，不僅在實體瘤中，而且在血液系統惡性腫瘤中。

目錄

第1章 調查手法

第2章 RNA聚合酵素I的簡介

• RNA聚合酵素I的概要與生物學的作用
• 腫瘤形成的核仁壓力和核糖體生物合成的重要性

第3章 RNA聚合酵素I為目標的機制的基礎

• 標靶RNA聚合酶I的原理
• RNA聚合酶I的直接抑制與間接調控

第4章 RNA聚合酵素I為目標的方法

• 低分子抑制劑
• 多劑聯合治療

第5章 成為RNA聚合酵素I阻礙的對象的疾病領域

• 腫瘤學
  • 造血惡性腫瘤
  • 固態腫瘤
• 新的適應症

第6章 RNA聚合酵素I抑制劑的臨床試驗:企業，國家，適應症，各相

• 研究
• 第一階段
• 第二階段

第7章 RNA聚合酵素I抑制劑的全球市場概要

• 目前市場情勢
• 未來的研究開發與商業機會

第8章 RNA聚合酵素I抑制劑市場動態

• 促進因素和機會
• 課題與阻礙因素

第9章 競爭情形

• 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