CAMBRIDGE, England & BOSTON--(BUSINESS WIRE)--Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle®) technology, today announced that emerging Phase 1/2 clinical pharmacokinetic (PK) and safety data for Bicycle Toxin Conjugates® (BTC® molecules) BT8009 and BT5528 demonstrating differentiated safety and tolerability profiles will be presented at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4 in Chicago.

英国剑桥和波士顿——（商业新闻短讯）——Bicycle Therapeutics plc（纳斯达克股票代码：BCYC）是一家制药公司，该公司基于其专有的双环肽（Bicycle®）技术开创了一类新的差异化治疗剂，今天宣布，将于5月31日至6月4日在芝加哥举行的2024年美国临床肿瘤学会（ASCO）年会上公布新出现的1/2期临床药代动力学（PK）和自行车毒素偶联物®（BTC®分子）BT8009和BT5528的安全性数据，证明其差异化的安全性和耐受性。

The company also announced zelenectide pevedotin as the International Nonproprietary Name (INN) for BT8009, and U.S. Food and Drug Administration (FDA) Fast Track Designation granted to BT5528 for the treatment of adult patients with previously treated, locally advanced or metastatic urothelial cancer (mUC)..

该公司还宣布zelenectide pevedotin为BT8009的国际非专有名称（INN），美国食品和药物管理局（FDA）授予BT5528快速通道指定，用于治疗先前接受过治疗的局部晚期或转移性尿路上皮癌（mUC）的成年患者。。

“As we advance the development of our investigational therapies, we are pleased to see the underlying characteristics of Bicycle® molecules developed using our platform technology — small size for rapid tissue penetration, tunable pharmacokinetics and high target selectivity — are leading to emerging differentiated clinical profiles that we believe have the potential to provide enhanced benefits and quality of life for cancer patients who have advanced disease,” said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics.

Bicycle Therapeutics首席执行官凯文·李博士说：“随着我们推进研究疗法的发展，我们很高兴看到使用我们的平台技术开发的Bicycle®分子的潜在特征-快速组织穿透的小尺寸，可调节的药代动力学和高靶点选择性-正在导致新出现的差异化临床特征，我们认为这些特征有可能为患有晚期疾病的癌症患者提供更好的益处和生活质量。”。

“At ASCO, we look forward to presenting preliminary clinical pharmacokinetic and safety data for our Bicycle Toxin Conjugates zelenectide pevedotin, formerly BT8009, and BT5528 that show substantial differences in their pharmacokinetic profiles compared to antibody drug conjugates. Additionally, we continue to advance enrollment and site activation for our Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in mUC and prepare for multiple clinical and program updates in the second half of 2024.

“在ASCO，我们期待着为我们的自行车毒素缀合物zelenectide pevedotin（以前称为BT8009）和BT5528提供初步的临床药代动力学和安全性数据，与抗体-药物缀合物相比，它们的药代动力学特征显示出显着差异。此外，我们继续推进mUC中zelenectide pevedotin的2/3期Duravelo-2注册试验的注册和网站激活，并为2024年下半年的多项临床和计划更新做好准备。

These include updates from the Phase 1/2 clinical trials of zelenectide pevedotin and BT5528, for which the newly awarded FDA Fast Track Designation demonstrates the continued need for targeted therapies for patients living with advanced bladder cancer.”.

这些包括zelenectide pevedotin和BT5528的1/2期临床试验的更新，为此，新获得的FDA快速通道指定表明，晚期膀胱癌患者仍需要针对性治疗。”。

PK and Safety Data from BTC® Molecules

BTC®分子的PK和安全性数据

Title: Breaking from the paradigm of antibody-drug conjugates: Evaluation of clinical pharmacokinetics and safety of Bicycle Toxin Conjugates (BTCs)

标题：打破抗体-药物偶联物的范式：自行车毒素偶联物（BTC）的临床药代动力学和安全性评估

Poster Session Title: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology

海报会议标题：发育疗法-分子靶向药物和肿瘤生物学

Date and Time: Saturday, June 1, at 9 a.m. CT

日期和时间：6月1日星期六上午9点

Abstract Number: 3088

摘要编号：3088

Speaker/Lead Author: Justin Bader, Pharm.D., MBA, Bicycle Therapeutics

演讲者/主要作者：JustinBader，Pharm.D.，MBA，自行车治疗学

Bicycle Therapeutics researchers and collaborators sought to compare PK behavior for BTC molecules to MMAE-containing antibody drug conjugate (ADC) enfortumab vedotin (EV). To do this, the researchers developed PK models and simulated PK exposures over a 28-day cycle for zelenectide pevedotin (5 mg/m2 once weekly) and BT5528 (5 mg/m2 once weekly) and compared them to published PK parameters for EV (1.25 mg/kg on Days 1, 8 and 15 of a 28-day cycle).

自行车治疗研究人员和合作者试图比较BTC分子与含MMAE的抗体-药物偶联物（ADC）enfortumab vedotin（EV）的PK行为。为此，研究人员开发了PK模型，并模拟了zelenectide pevedotin（每周一次5 mg/m2）和BT5528（每周一次5 mg/m2）在28天周期内的PK暴露，并将其与EV公布的PK参数进行了比较（28天周期的第1,8和15天为1.25 mg/kg）。

Results showed:.

结果显示：。

BTC molecule half-life is substantially shorter than that of EV (<1 hour vs 3.6 days), resulting in extensive elimination of the BTC molecule within hours of dose administration rather than weeks. MMAE half-life is also shorter following BTC molecule administration relative to EV (1.9 days vs 2.6 days)​, potentially due to a slower rate of MMAE release from the ADC..

BTC分子的半衰期比EV短得多（<1小时vs 3.6天），导致BTC分子在给药数小时内而不是数周内被广泛消除。相对于EV，BTC分子给药后MMAE的半衰期也较短（1.9天比2.6天）​, 可能是由于ADC释放MMAE的速度较慢。。

Relative to EV, BTC molecules achieved similar unconjugated MMAE PK exposure over a ​28-day cycle while maximum serum concentration (Cmax) was elevated for unconjugated MMAE, potentially driving rapid penetration into tumor tissue.

相对于EV，BTC分子在a上实现了类似的非共轭MMAE PK暴露​28天的周期，而未结合的MMAE的最大血清浓度（Cmax）升高，可能导致快速渗透到肿瘤组织中。

Relative to EV, conjugated MMAE PK exposure from BTC molecules was substantially lower, potentially limiting toxicities.

相对于EV，来自BTC分子的缀合MMAE PK暴露显着降低，可能限制毒性。

Zelenectide pevedotin and BT5528 continued to show promising emerging safety and tolerability profiles, with data to be presented from all patients dosed at Cycle 1 Day 1 with zelenectide pevedotin 5 mg/m2 once weekly monotherapy (data as of March 22, 2024) and with BT5528 6.5 mg/m2 every two weeks monotherapy (data as of March 14, 2024).

Zelenectide pevedotin和BT5528继续显示出有希望的新出现的安全性和耐受性概况，所有患者在第1周期第1天服用Zelenectide pevedotin 5 mg/m2，每周一次单药治疗（截至2024年3月22日的数据），BT5528每两周服用6.5 mg/m2单药治疗（截至2024年3月14日的数据）。

The findings:.

调查结果：。

Zelenectide pevedotin-related adverse events (AEs) occurred in 84% of patients, of which 31% were Grade ≥3.

Zelenectide pevedotin相关不良事件（AE）发生率为84%，其中31%为≥3级。

BT5528-related AEs occurred in 91% of patients, of which 22% were Grade ≥3.

91%的患者发生BT5528相关AE，其中22%为≥3级。

In contrast to ADCs, treatment-related AEs of interest such as peripheral neuropathy, skin reactions, ocular disorders and hyperglycemia occurred at relatively low frequency and severity with both BTC molecules.

与ADC相反，与治疗相关的感兴趣的AE，例如周围神经病变，皮肤反应，眼部疾病和高血糖症，在两种BTC分子中发生的频率和严重程度相对较低。

Trial-in-Progress: Registrational Phase 2/3 Duravelo-2 Study

正在进行的试验：注册阶段2/3 Duravelo-2研究

Title: A phase 2/3 study of Bicycle Toxin Conjugate BT8009 targeting Nectin-4 in patients with locally advanced or metastatic urothelial cancer (la/mUC): Duravelo-2

标题：局部晚期或转移性尿路上皮癌（la/mUC）患者靶向Nectin-4的自行车毒素结合物BT8009的2/3期研究：Duravelo-2

Poster Session Title: Genitourinary Cancer – Kidney and Bladder

海报主题：泌尿生殖系统癌症-肾脏和膀胱

Date and Time: Sunday, June 2, at 9 a.m. CT

日期和时间：6月2日星期日上午9点

Abstract Number: TPS4619

摘要编号：TPS4619

Speaker/Lead Author: Yohann Loriot, M.D., Ph.D., Institut de Cancérologie Gustave Roussy, Université Paris-Saclay

演讲者/主要作者：Yohann Loriot，医学博士，博士，巴黎萨克莱大学癌症研究所Gustave Roussy

The posters will be made available in the Publications section of bicycletherapeutics.com following the presentations.

演示后，海报将在bicycletherapeutics.com的出版物部分提供。

About Bicycle Therapeutics

关于自行车疗法

Bicycle Therapeutics is a clinical-stage pharmaceutical company developing a novel class of medicines, referred to as Bicycle® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry.

Bicycle Therapeutics是一家临床阶段的制药公司，开发了一类新型药物，称为Bicycle®分子，用于治疗现有疗法服务不足的疾病。自行车分子是完全合成的短肽，受小分子支架的约束，形成两个稳定其结构几何形状的环。

This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating zelenectide pevedotin, previously BT8009, a Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials.

这种限制促进了具有高亲和力和选择性的靶标结合，使自行车分子成为药物开发的有吸引力的候选物。该公司正在评估zelenectide pevedotin，以前是BT8009，一种靶向Nectin-4（一种经过充分验证的肿瘤抗原）的Bicycle®毒素偶联物（BTC®）；BT5528，一种靶向EphA2的BTC分子，EphA2是一种历史上不可药用的靶标；和BT7480，一种靶向Nectin-4和激动CD137的自行车肿瘤靶向免疫细胞激动剂®（Bicycle-TICA®），在公司赞助的临床试验中。

Additionally, the company is developing Bicycle® Radio Conjugates (BRC™) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle® technology to develop therapies for diseases beyond oncology..

此外，该公司正在开发用于放射性药物的Bicycle®放射性结合物（BRC™），并通过各种合作伙伴关系，探索使用Bicycle®技术开发肿瘤以外疾病的治疗方法。。

Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit bicycletherapeutics.com.

Bicycle Therapeutics总部位于英国剑桥，其领导团队的许多关键职能和成员位于马萨诸塞州剑桥。有关更多信息，请访问bicycletherapeutics.com。

Forward Looking Statements

前瞻性声明

This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words.

本新闻稿可能包含根据1995年《私人证券诉讼改革法案》安全港条款所作的前瞻性声明。这些陈述可以用“目标”、“预期”、“相信”、“可能”、“估计”、“预期”、“预测”、“目标”、“打算”、“可能”、“计划”、“可能”、“潜在”、“寻求”、“将”等词语以及这些词语的变体或旨在识别前瞻性陈述的类似表达来识别，尽管并非所有前瞻性陈述都包含这些词语。

Forward-looking statements in this press release include, but are not limited to, statements regarding Bicycle’s anticipated progress across its R&D pipeline and the advancement of its product candidates, including zelenectide pevedotin, BT5528 and BT7480; the anticipated progression of Bicycle’s clinical trials and the availability of and timing of announcement of data from clinical trials and program updates for clinical candidates; the development of potential radiopharmaceutical or other product candidates using Bicycle’s technology through various partnerships; the therapeutic potential for Bicycles in oncology and other applications; and Bicycle’s participation in the ASCO annual meeting.

本新闻稿中的前瞻性声明包括但不限于关于自行车在整个研发流程中的预期进展及其候选产品（包括zelenectide pevedotin，BT5528和BT7480）的进展的声明；自行车临床试验的预期进展以及临床试验和临床候选人计划更新数据的可用性和发布时间；通过各种合作关系，利用自行车技术开发潜在的放射性药物或其他候选产品；自行车在肿瘤学和其他应用中的治疗潜力；和自行车参加ASCO年会。

Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle’s product candidates; .

自行车可能无法真正实现这些前瞻性声明中披露的计划、意图或期望，您不应过度依赖这些前瞻性声明。由于各种因素，实际结果或事件可能与这些前瞻性声明中披露的计划、意图和期望存在重大差异，包括：研究和开发以及临床试验的启动、进展和完成以及自行车候选产品的临床开发中固有的不确定性。