Accent Therapeutics在2025年AACR年会上展示了支持首创DHX9抑制剂ATX-559和新型KIF18A抑制剂ATX-295治疗潜力的数据-动脉网

Accent Therapeutics Presents Data Supporting Therapeutic Potential of First-in-Class DHX9 Inhibitor, ATX-559, and Novel KIF18A Inhibitor, ATX-295, at the AACR Annual Meeting 2025

CISION 等信源发布 2025-04-29 03:30

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ATX-559, a first-in-class oral DHX9 inhibitor, shown to induce potent and selective tumor growth inhibition in preclinical models of cancers with high genomic instability and replication stress

ATX-559，一种首创的口服DHX9抑制剂，在具有高基因组不稳定性和复制应激的癌症临床前模型中显示出强大且选择性的肿瘤生长抑制作用。

Oral presentation showcases robust, selective activity of potentially best-in-class KIF18A inhibitor, ATX-295, in KIF18A-dependent ovarian cancer models exhibiting whole genome doubling

口头报告展示了潜在的最佳同类KIF18A抑制剂ATX-295在表现出全基因组加倍的KIF18A依赖性卵巢癌模型中强劲且选择性的活性。

LEXINGTON, Mass.

列克星敦，马萨诸塞州

，

April 28, 2025

2025年4月28日

/PRNewswire/ -- Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, today announced new preclinical data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, in poster and oral presentations, respectively, at the AACR Annual Meeting 2025 taking place .

/PRNewswire/ -- 临床阶段生物制药公司Accent Therapeutics，专注于开发新型、靶向的小分子癌症治疗药物，今日宣布了其首创的口服DHX9抑制剂ATX-559和潜在最佳的KIF18A抑制剂ATX-295的新临床前数据，分别以海报和口头报告的形式在2025年举行的AACR年会上展示。

April 25-30

4月25日至30日

在

Chicago, Illinois

伊利诺伊州芝加哥市

. ATX-559 and ATX-295 are currently under investigation in Phase 1/2 clinical trials.

ATX-559 和 ATX-295 目前正在 1/2 期临床试验中进行研究。

'Our presentations at the AACR annual meeting showcase the outputs of Accent's precision oncology approach to drug development, with strong foundational data that inform our current and future clinical development plans for our lead programs, ATX-559 and ATX-295,' said

“我们在AACR年会上的报告展示了Accent在药物开发中采用精准肿瘤学方法的成果，这些报告包含了有力的基础数据，为我们的主要项目ATX-559和ATX-295当前及未来的临床开发计划提供了指导。”

Serena Silver

赛琳娜·西尔弗

, Ph.D., Chief Scientific Officer of Accent Therapeutics. 'These preclinical data reinforce our assets' therapeutic potential across several cancer indications with high unmet need.'

博士，Accent Therapeutics首席科学官。'这些临床前数据加强了我们在多种具有高度未满足需求的癌症适应症中的治疗潜力。'

The company's poster presentation includes preclinical data supporting continued clinical evaluation of ATX-559, a first-in-class potent, selective, and orally bioavailable small-molecule inhibitor of DHX9. Results within characterize the compound's activity in cancer cell lines with genomic instability and elevated replication stress spanning several indications, including dMMR/MSI-H colorectal cancer and BRCA-altered triple negative breast cancer, and in subtypes of lung, gastric, ovarian, and prostate cancers.

公司海报展示的内容包括支持继续对ATX-559进行临床评估的临床前数据，ATX-559是一种首创的强效、选择性且口服生物利用度高的DHX9小分子抑制剂。结果表明，该化合物在具有基因组不稳定和复制压力增高的多种癌症细胞系中显示出活性，涵盖的适应症包括错配修复缺陷/高微卫星不稳定性（dMMR/MSI-H）结直肠癌和BRCA突变三阴性乳腺癌，以及肺癌、胃癌、卵巢癌和前列腺癌的亚型。

ATX-559 was shown to be well tolerated .

ATX-559 显示出良好的耐受性。

in vivo

体内

, leading to robust and dose dependent tumor growth inhibition and regression in BRCA deficient breast cancer and dMMR/MSI-H cell- and patient-derived xenograft models.

，导致BRCA缺陷型乳腺癌和dMMR/MSI-H细胞及患者来源的异种移植模型中强劲且剂量依赖性的肿瘤生长抑制和消退。

ATX-559 is currently under investigation in a first-in-human, Phase 1/2, open-label, dose-escalation and expansion study, with a focus on advanced or metastatic patients with BRCA-1 and/or BRCA-2-deficient breast cancer or MSI-H and/or dMMR solid tumors (

ATX-559目前正在一项首次人体、1/2期、开放标签、剂量递增和扩展研究中进行调查，重点是BRCA-1和/或BRCA-2缺陷型乳腺癌或MSI-H和/或dMMR实体瘤的晚期或转移患者 (

NCT06625515

). Additional undisclosed solid tumor indications undergoing replicative stress and representing significant patient populations may be explored either in parallel or in subsequent studies.

）。其他未公开的实体瘤适应症，这些患者群体显著且正在经历复制压力，可能在平行或后续研究中进行探索。

For Accent's second lead program, preclinical data included in the company's oral presentation demonstrates sensitivity to KIF18A inhibition across several solid tumor indications with high chromosomal instability, signaling significant opportunity for patient impact by leveraging KIF18A as a selective oncology target.

对于Accent的第二个主导项目，公司口头报告中包含的临床前数据展示了在多个具有高染色体不稳定性实体瘤适应症中对KIF18A抑制的敏感性，这表明通过将KIF18A作为选择性肿瘤靶点，有望对患者产生重大影响。

Results further characterize ATX-295 as a potent and selective KIF18A inhibitor capable of inducing mitotic arrest, cell death, and anti-tumor activity in cancer models with high chromosomal instability. Studies in relevant cellular and xenograft models exhibiting whole genome doubling confirm selective anti-cancer activity, providing rationale for whole genome doubling as a predictive biomarker of ATX-295 sensitivity in ovarian and triple negative breast cancer..

结果进一步表明，ATX-295是一种强效且选择性的KIF18A抑制剂，能够在具有高染色体不稳定性的癌症模型中诱导有丝分裂停滞、细胞死亡和抗肿瘤活性。在表现出全基因组加倍的相关细胞和异种移植模型中的研究证实了其选择性抗癌活性，为全基因组加倍作为预测ATX-295在卵巢癌和三阴性乳腺癌中敏感性的生物标志物提供了理论依据。

Accent recently initiated clinical evaluation of ATX-295 in a first-in-human Phase 1/2 open-label, dose-escalation and expansion study designed to evaluate the molecule's safety, tolerability, and preliminary efficacy in patients with locally advanced or metastatic solid tumors, including high-grade serious ovarian cancer (.

Accent最近启动了ATX-295的临床评估，这是一项首次在人体内进行的1/2期开放标签、剂量递增和扩展研究，旨在评估该分子在局部晚期或转移性实体瘤（包括高级别严重卵巢癌）患者中的安全性、耐受性和初步疗效。

NCT06799065

）。

Details for the presentations are as follows:

演示文稿的详细信息如下：

Presentation Title:

演示标题：

Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models

新型KIF18A抑制剂ATX-295在全基因组倍增的卵巢癌临床前模型中活性增强

Abstract Number

摘要编号

: 3784

：3784

Session Type

会话类型

: Minisymposium

小型研讨会

Session Title

会议标题

: Novel Antitumor Agents

新型抗肿瘤药物

Session Date and Time

会话日期和时间

：

Monday, April 28

4月28日，星期一

，

2:30 pm

下午2点30分

–

4:30 pm CT

下午4点30分（中部时间）

Location

位置

: Room S103 - McCormick Place South (Level 1)

：S103室 - 麦考密克会展中心南馆（1层）

Presenter

主持人

：

Maureen Lynes

莫林·莱恩斯

, Ph.D.

，博士

Poster Title:

海报标题：

ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress

ATX-559，首创的DHX9抑制剂，以及针对具有基因组不稳定性和复制压力的分子定义肿瘤的靶向治疗药物

Abstract Number

摘要编号

: 1758

：1758

Session Title

会话标题

: Novel Antitumor Agents 1

：新型抗肿瘤药物 1

Session Date and Time

会话日期和时间

：

Monday, April 28

4月28日，星期一

，

9:00 am

上午9:00

–

12:00 pm CT

中午12点（美国中部时间）

Location:

位置：

Poster Section 22

海报部分 22

Poster Board Number

海报板编号

: 10

：10

Presenter

主持人

：

Jennifer Castro

詹妮弗·卡斯特罗

About ATX-559

关于ATX-559

ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need.

ATX-559 是一种首创的强效且选择性的 DHX9 抑制剂，DHX9 是一种新型的、之前未被药物靶向的 RNA 和 DNA/RNA 解旋酶，已被证明在具有高水平复制应激的肿瘤（包括乳腺癌、卵巢癌、结直肠癌、子宫内膜癌、胃癌等）中发挥关键作用，代表了具有显著未满足医疗需求的广大患者群体。

DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients.

DHX9 已被报道在复制、转录、翻译、RNA剪接、RNA加工和基因组稳定性维持中发挥重要作用，使其成为一个引人注目的新型肿瘤学靶点。除了利用DNA修复缺陷背景（例如BRCA）和高突变状态（例如MSI-H/dMMR）中的关键肿瘤脆弱性外，Accent还在探索其他肿瘤类型对DHX9抑制的敏感性，以及将DHX9抑制剂与其他癌症治疗方法结合的潜力，以充分发挥其帮助患者的全部潜力。

Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial .

Accent 保留了 ATX-559 的全球完整权利，该药物目前正在进行 1/2 期临床试验评估。

(NCT06625515)

, and the DHX9 program.

，以及 DHX9 计划。

About ATX-295

关于ATX-295

Accent's second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells.

Accent的第二个主导项目是一种潜在的最佳KIF18A抑制剂，可能针对包括卵巢癌和三阴性乳腺癌（TNBC）在内的多种癌症适应症的广大患者群体。KIF18A是一种有丝分裂驱动蛋白马达蛋白，在具有染色体不稳定的特定肿瘤中对细胞分裂至关重要，但在健康细胞中并不重要。

KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) .

KIF18A抑制剂治疗会导致染色体数目异常（非整倍体）的癌细胞快速死亡。

in vitro

体外

and

和

in vivo

体内

, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to ATX-295, which is currently being evaluated in a Phase 1/2 clinical trial (

，而染色体数目正常的细胞（整倍体）则不受影响。Accent 拥有 ATX-295 的全球全部权利，该药物目前正在进行 1/2 期临床试验评估 (

NCT06799065

), and the KIF18A program.

），以及KIF18A程序。

About Accent Therapeutics

关于Accent Therapeutics

Accent Therapeutics is pioneering a new class of small molecule precision cancer therapies targeting critical intracellular dependencies that span multiple types of cancer. Building upon industry-leading expertise in RNA-modifying proteins (RMPs) and the systematic mapping of both the RMP space and adjacent high-value areas for drug discovery, the company employs a flexible model that allows for a diversity of approaches to developing potentially transformative biomarker-driven cancer medicines.

Accent Therapeutics正在开创一类新的小分子精准癌症治疗方法，针对多种癌症中关键的细胞内依赖性。基于在RNA修饰蛋白（RMP）领域的行业领先专业知识，并系统地绘制了RMP领域及邻近高价值药物发现区域，该公司采用灵活的模式，允许通过多样化的途径开发潜在变革性的生物标志物驱动型癌症药物。

Accent's therapies are designed for both novel and known, but suboptimally addressed, high-impact oncology targets with the potential to benefit large patient populations with significant unmet need. For more information on Accent's mission to translate extraordinary science into life-changing therapeutics for patients living with cancer, visit .

Accent的疗法设计针对新颖且已知但未得到最佳解决的高影响力肿瘤靶点，这些靶点有潜力使具有显著未满足需求的广大患者群体受益。如需了解更多关于Accent致力于将非凡科学转化为改变生命的癌症患者治疗方法的信息，请访问。

www.accenttx.com

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阿曼达·塞勒斯

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