SAN DIEGO--(BUSINESS WIRE)--Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, presents preclinical and clinical pharmacodynamic data on its lead ecDNA-directed therapy (ecDTx), BBI-355, and research on ecDNA-mediated acquired resistance to chemotherapy at the American Association for Cancer Research (AACR) Annual Meeting 2024.

圣地亚哥--（商业新闻短讯）--无限生物（Nasdaq:BOLD），一家临床阶段的肿瘤公司，正在研究染色体外DNA（ecDNA）生物学，为以前难治的癌基因扩增癌症患者提供转化疗法，在2024年美国癌症研究协会（AACR）年会上介绍了其主要的ecDNA定向疗法（ecDTx），BBI-355的临床前和临床药效学数据，以及ecDNA介导的获得性化疗耐药研究。

BBI-355 is a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial in patients with oncogene amplified cancers..

BBI-355是一种新型的口服选择性检查点激酶1（CHK1）抑制剂，正在进行癌基因扩增癌症患者的1/2期临床试验。。

“Extrachromosomal DNA afford unique advantages to tumors, typically rendering existing therapies ineffective and correlating with poor patient outcomes,” said Chris Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. “Our first poster presented this year at AACR demonstrated that BBI-355 overcame ecDNA-mediated targeted therapy resistance in preclinical tumor models by leveraging the enhanced reliance of ecDNA-driven tumor cells on CHK1 for survival.

“染色体外DNA为肿瘤提供了独特的优势，通常使现有疗法无效，并与不良的患者预后相关，”无限生物首席科学官Chris Hassig博士说。“我们今年在AACR上发布的第一张海报表明，BBI-355通过利用ecDNA驱动的肿瘤细胞对CHK1的生存依赖性增强，克服了临床前肿瘤模型中ecDNA介导的靶向治疗耐药性。

BBI-355 showed substantial antitumor activity, including complete and durable regressions, in preclinical oncogene amplified models..

BBI-355在临床前癌基因扩增模型中显示出显着的抗肿瘤活性，包括完全和持久的消退。。

Dr. Hassig continued, “Today we present preclinical and preliminary clinical pharmacodynamic biomarker assay data that showed detection of CHK1 inhibition-associated replication stress in both patient skin and tumor tissue following administration of BBI-355. In addition, we report a possible role for ecDNA in acquired resistance to chemotherapy observed in preclinical models, extending the potential applicability of ecDNA-directed strategies beyond targeted therapy resistance.

Hassig博士继续说道：“今天，我们提供了临床前和初步的临床药效学生物标志物测定数据，显示在服用BBI-355后，患者皮肤和肿瘤组织中均检测到CHK1抑制相关的复制应激。此外，我们报告了ecDNA在临床前模型中观察到的获得性化疗耐药性中的可能作用，将ecDNA指导策略的潜在适用性扩展到靶向治疗耐药性之外。

We are encouraged by these findings as we continue to advance BBI-355 through the ongoing Phase 1/2 POTENTIATE clinical trial.”.

我们对这些发现感到鼓舞，因为我们继续通过正在进行的1/2期强化临床试验推进BBI-355。”。

Details of the presentations are as follows:

演示的详细信息如下：

Title: Oral CHK1 inhibitor BBI-355 allows flexibility of dose and schedule with demonstration of monotherapy and combinational antitumor activity in extrachromosomal DNA (ecDNA)-driven oncogene amplified preclinical models

标题：口服CHK1抑制剂BBI-355可以灵活调整剂量和时间表，并在染色体外DNA（ecDNA）驱动的癌基因扩增临床前模型中证明单一疗法和联合抗肿瘤活性

Abstract Number: 613

摘要编号：613

Session Category: Experimental and Molecular Therapeutics

课程类别：实验和分子疗法

Session Title: Kinase and Phosphatase Inhibitors 1

会议标题：激酶和磷酸酶抑制剂1

Session Date and Time: Sunday Apr 7, 2024, 1:30 PM – 5:00 PM PT

会议日期和时间：2024年4月7日星期日下午1:30-下午5:00

Location: Poster Section 25

位置：海报第25节

Poster Board Number: 23

海报板编号：23

BBI-355 showed inhibition of CHK1 in a host of tumor cell lines and demonstrated in vivo single agent tumor growth inhibition, including complete tumor regressions, across a range of tumor models representing multiple different oncogene amplifications and tumor types. BBI-355 also demonstrated synergistic tumor growth inhibition, including durable regressions, when combined with targeted therapies across multiple oncogene amplified tumor models..

BBI-355在许多肿瘤细胞系中显示出对CHK1的抑制作用，并在代表多种不同癌基因扩增和肿瘤类型的一系列肿瘤模型中证明了体内单药肿瘤生长抑制，包括完全肿瘤消退。当与多种癌基因扩增的肿瘤模型中的靶向治疗相结合时，BBI-355还表现出协同的肿瘤生长抑制作用，包括持久的消退。。

Title: Preclinical and clinical pharmacodynamic characterization of BBI-355, a novel, orally bioavailable, and selective CHK1 inhibitor being evaluated in the first-in-human Phase 1/2 POTENTIATE clinical trial of patients with cancer harboring oncogene amplifications

标题：BBI-355的临床前和临床药效学表征，BBI-355是一种新型的口服生物利用度和选择性CHK1抑制剂，正在对携带癌基因扩增的癌症患者进行首次人体1/2期强化临床试验

Number: 3631

编号：3631

Session Category: Clinical Research

课程类别：临床研究

Session Title: Biomarkers in Clinical Trials

会议标题：临床试验中的生物标志物

Session Date and Time: Monday Apr 8, 2024, 1:30 PM - 5:00 PM PT

Session Date and Time: Monday Apr 8, 2024, 1:30 PM - 5:00 PM PT

Location: Poster Section 40

位置：海报第40节

Poster Board Number: 9

海报板编号：9

Historically, clinical CHK1 inhibitor programs have lacked effective clinical PD biomarker assays. The findings showed that phosphorylated-CHK1 Ser345 (pCHK1-S345) is a useful pharmacodynamic (PD) biomarker for confirming clinical on-target activity of BBI-355 and could potentially inform the pharmacologically active range of BBI-355 in clinical development.

历史上，临床CHK1抑制剂计划缺乏有效的临床PD生物标志物测定。研究结果表明，磷酸化CHK1 Ser345（pCHK1-S345）是一种有用的药效学（PD）生物标志物，可用于确认BBI-355的临床靶向活性，并可能在临床开发中告知BBI-355的药理活性范围。

In addition to preclinical data, increased pCHK1-S345 expression by immunohistochemistry in skin biopsies from patients treated with BBI-355 in the ongoing POTENTIATE clinical study were also observed, marking the first, real-time analysis of PD activity from a CHK1 inhibitor in humans..

除了临床前数据外，在正在进行的强化临床研究中，还观察到BBI-355治疗的患者皮肤活检组织中pCHK1-S345表达增加，这标志着首次对人类CHK1抑制剂的PD活性进行实时分析。。

Title: Extrachromosomal DNA (ecDNA) amplification of multi-drug resistance genes results in acquired resistance to taxane-based chemotherapy

标题：多药耐药基因的染色体外DNA（ecDNA）扩增导致对紫杉烷类化疗的获得性耐药

Abstract Number: 5870

摘要编号：5870

Session Category: Experimental and Molecular Therapeutics

课程类别：实验和分子疗法

Session Title: Mechanisms of Drug Resistance 3

课程名称：耐药机制3

Session Date and Time: Tuesday Apr 9, 2024, 1:30 PM - 5:00 PM PT

Session Date and Time: Tuesday Apr 9, 2024, 1:30 PM - 5:00 PM PT

Location: Poster Section 24

位置：海报第24节

Poster Board Number: 14

海报板编号：14

Early insights into the role of ecDNA in driving resistance to paclitaxel, a taxane chemotherapy, are revealed and highlight the importance of ecDNA-directed therapies as a potential treatment option for many patients that have chemotherapy-resistant disease. Chemotherapy remains standard of care for many cancer patients, however, resistance to chemotherapy often develops and has been associated with the emergence of multi-drug resistance (MDR) gene amplification, such as ABCB1.

揭示了ecDNA在驱动紫杉醇（一种紫杉烷化疗）耐药性中的作用的早期见解，并强调了ecDNA指导疗法作为许多化疗耐药疾病患者的潜在治疗选择的重要性。化疗仍然是许多癌症患者的标准治疗方法，然而，对化疗的耐药性经常发展，并且与多药耐药（MDR）基因扩增（如ABCB1）的出现有关。

These preclinical findings showed that ecDNA-enabled MDR gene amplification can cause short-and long-term resistance to paclitaxel, potentially driving resistance to chemotherapy in patients and underscoring the broad need for ecDTx for chemotherapy-resistant patient populations..

这些临床前研究结果表明，ecDNA激活的MDR基因扩增可引起对紫杉醇的短期和长期耐药性，可能导致患者对化疗的耐药性，并强调了化疗耐药患者群体对ecDTx的广泛需求。。

About BBI-355

关于BBI-355

Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in patients with oncogene amplified cancers. CHK1 is a master regulator of cells’ response to replication stress (RS).

Boundless Bio的主要ecDNA定向疗法（ecDTx）BBI-355是一种新型的口服选择性检查点激酶1（CHK1）抑制剂，正在进行中的首次人类1/2期强化临床试验（NCT05827614）中研究癌基因扩增癌症患者。CHK1是细胞对复制应激（RS）反应的主要调节因子。

RS is elevated in ecDNA-enabled oncogene amplified cancer cells and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells..

RS在ecDNA激活的癌基因扩增的癌细胞中升高，因此代表了这些细胞的关键脆弱性。BBI-355旨在通过破坏调节RS的适当CHK1功能，从而促进灾难性RS相对于健康细胞优先杀死癌细胞，从而利用ecDNA致癌基因扩增的癌细胞中升高的RS。。

About Boundless Bio

关于无限生物

Boundless Bio is a clinical-stage oncology company dedicated to unlocking a new paradigm in cancer therapeutics to address the significant unmet need of patients with oncogene amplified tumors by targeting extrachromosomal DNA (ecDNA), a root cause of oncogene amplification and observed in more than 14% of cancer patients.

Boundless Bio是一家临床阶段的肿瘤学公司，致力于开启癌症治疗的新范式，通过靶向染色体外DNA（ecDNA）来解决癌基因扩增肿瘤患者的重大未满足需求，这是癌基因扩增的根本原因，并且在超过14%的癌症患者中观察到。

Boundless Bio is developing the first ecDNA-directed therapy (ecDTx), BBI-355, which is an oral inhibitor of checkpoint kinase 1 (CHK1) and is being evaluated in a Phase 1/2 clinical trial in patients with oncogene amplified cancers. Boundless Bio’s second ecDTx, BBI-825, is an oral inhibitor of ribonucleotide reductase (RNR) and recently entered a Phase 1/2 clinical trial in cancer patients with resistance gene amplifications.

Boundless Bio正在开发第一种ecDNA定向疗法（ecDTx），BBI-355，它是检查点激酶1（CHK1）的口服抑制剂，正在癌基因扩增癌症患者的1/2期临床试验中进行评估。Boundless Bio的第二个ecDTx BBI-825是核糖核苷酸还原酶（RNR）的口服抑制剂，最近在耐药基因扩增的癌症患者中进入了1/2期临床试验。

Leveraging its Spyglass platform, Boundless Bio has additional programs advancing through preclinical development and discovery. Boundless Bio is headquartered in San Diego, CA..

利用其Spyglass平台，无限生物拥有通过临床前开发和发现推进的其他项目。无限生物总部位于加利福尼亚州圣地亚哥。