This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with previously treated NECTIN4-amplified advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior line of systemic therapy in the advanced/metastatic setting (see inclusion criteria below). The study will comprise of 2 cohorts: Cohort A (non-squamous NSCLC) and Cohort B (squamous NSCLC).

开始日期2025-07-18

申办/合作机构

Bicycle Therapeutics Plc

NCT06840483

/ Active, not recruiting临床2期

Phase 2 Study of Zelenectide Pevedotin in Participants With NECTIN4 Amplified Advanced Breast Cancer

This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with NECTIN4-amplified recurrent, unresectable, or metastatic breast cancer who have received prior therapy (see inclusion criteria below). The study will comprise of 2 cohorts. Cohort A will include participants with hormone receptor positive/ human epidermal growth factor receptor 2 negative [HR+/HER2-] breast cancer, whereas Cohort B will include participants with triple-negative breast cancer (TNBC).

开始日期2025-03-03

申办/合作机构

Bicycle Therapeutics Plc

100 项与 Zelenectide pevedotin 相关的临床结果

登录后查看更多信息

100 项与 Zelenectide pevedotin 相关的转化医学

登录后查看更多信息

100 项与 Zelenectide pevedotin 相关的专利（医药）

登录后查看更多信息

533

项与 Zelenectide pevedotin 相关的文献（医药）

2025-12-31·mAbs

A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity

Article

作者: Gesner, Thomas ; Logel, Claude ; Xie, Kathleen T. ; Cebe, Regis ; Wu, Nila C. ; Li, Xun ; Shi, Xingyi ; Velazquez, Roberto ; Simmons, Quincey ; Tschantz, William R. ; Korn, Joshua ; Barzaghi-Rinaudo, Patrizia ; Sagar, Vivek ; Hainzl, Dominik ; Malamas, Anthony ; Mercan, Samuele ; Green, Andrew ; McLaughlin, Margaret ; Huber, Thomas ; Mueller, Kathrin ; D’Alessio, Joseph A. ; Synan, Alyssa

P-cadherin (pCAD) and LI-cadherin (CDH17) are cell-surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dual targeting approach using an antibody-drug conjugate (ADC). In this study, we used a unique avidity-driven in vitro screening approach to generate pCAD x CDH17 bispecific antibodies that selectively target cells expressing both antigens over cells expressing only pCAD or only CDH17. Based on in vitro binding and inhibition of cell proliferation results, we selected a lead bispecific antibody to link to the cytotoxic payload monomethyl auristatin E (MMAE) to generate a pCAD x CDH17 bispecific MMAE ADC. In in vivo dual flank mouse models, we demonstrated antitumor activity of the bispecific ADC in tumors expressing both antigens but not in tumors expressing only pCAD or only CDH17. Overall, the preclinical data presented here support the proof-of-concept bispecific antibody discovery approach, demonstrating a rational design for screening antibodies by prioritizing cross-arm avid IgGs to target dual-positive cells.

2025-11-01·BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis and antitumor evaluation of a novel nectin-4 targeting bicyclic toxin conjugate

Article

作者: Ma, Xian-Li ; Zhang, Ye ; Liu, Feng ; Song, Yun-Song ; Huang, Yang-Qing ; Gu, Jia-Ning ; Ding, Hai-Feng ; Feng, Xiang-Yang

A Nectin-4 targeting bicyclic toxin conjugate (BTC) BGC1614 was designed, synthesized and evaluated as an antitumor agent. Fluorescence-activated cell sorting (FACS) assay results indicated that BGC1614 exhibited selective and strong binding to Nectin-4-expressing cells in comparison with the clinical drug BT8009. Surface plasmon resonance (SPR) test showed that the equilibrium dissociation constants (K_D) for BT8009 and BGC1614 were 3.219 ± 0.412 × 10^-7 M and 3.859 ± 0.287 × 10^-7 M, respectively, indicating that BGC1614 exhibited similar target engagement capability with Nectin-4 compared to BT8009. In vivo antiproliferative activity assay results showed that BGC1614 (0.12 μM/kg) exhibited better antiproliferative activity than BT8009 (0.12 μM/kg, inhibition rate (IR) 87.6 %) in PC-3 (human prostate cancer cell) model with IR of 96.3 %, while BGC1614 (0.36 μM/kg) displayed similar inhibition with BT8009 (0.36 μM/kg, IR 72.7 %) in N87 (human gastric cancer cell) model with IR of 70.1 %, demonstrating that BGC1614 exhibited better antitumor effect in the same molar concentration in PC-3 model. In addition, BGC1614 was well-tolerated in efficacious doses in the nude model assays, while the pharmacokinetic (PK) parameters of BGC1614 were comparable to that of BT8009.

2025-06-12·ACS Medicinal Chemistry Letters

Site-Selective Anti-PD-L1 Antibody–MMAE Conjugate for Enhanced NSCLC Therapy

Article

作者: Kwon, Se Jeong ; Son, Jinyoung ; Chung, Sang J.

Nonsmall cell lung cancer (NSCLC) presents significant therapeutic challenges, causing advancements in targeted therapies. We have developed a site-selective antibody-drug conjugate (ADC), durvalumab-monomethyl auristatin E (MMAE), with a drug-antibody ratio (DAR) of 4, specifically targeting programmed death-ligand 1 (PD-L1), aimed at enhancing NSCLC therapy. Utilizing the innovative AbClick Pro linker, this ADC ensures stable, site-specific conjugation of MMAE to durvalumab, preserving antibody functionality and integrity. In vivo studies demonstrate that durvalumab-MMAE achieves substantial tumor growth inhibition in NSCLC xenograft models, with an impressive tumor growth inhibition rate of over 60% at lower dosages without significant toxicity. These results, combined with a favorable pharmacokinetic profile featuring extended half-life and low clearance, highlight the potential of durvalumab-MMAE (DAR4) as a potent next-generation ADC for treating PD-L1-expressing cancers, offering a promising avenue for improved NSCLC patient outcomes.

138

项与 Zelenectide pevedotin 相关的新闻（医药）

2026-05-03

·Bio药研新境

第114期：ADC之后，PDC如何炸穿实体瘤？国产药企中美双报破局（1）

原创日更｜ADC之后，PDC如何炸穿实体瘤？国产药企中美双报破局（1） 300 万癌症患者的痛点，化疗 / ADC 的短板被 PDC 补齐！每年数百万癌症患者面临化疗副作用噩梦，脱发呕吐只是冰山一角； ADC 虽实现靶向治疗，但大分子量导致肿瘤核心穿透受限，耐药率居高不下； PDC 横空出世！用 5-20 个氨基酸的 “微型导航”，带着毒药精准炸穿癌细胞，正常细胞零损伤！一、PDC 是什么？比 ADC 小 100 倍的 “智能快递”，3 组件缺一不可！核心逻辑：把 “靶向导航（多肽）+ 智能锁（连接子）+ 毒药包裹（载荷）” 打包，只送癌细胞！定义边界：严格意义上 PDC 的载荷为细胞毒性小分子，与载荷为放射性核素的 RDC、载荷为抗体的 ADC 属于不同偶联药物类别。组件通俗定位近 3 年临床核心要求靶向多肽癌细胞专属 “快递员” 纳摩尔级亲和力（结合够牢），低免疫原性（不被免疫系统攻击）连接子防拆 “智能锁” 血液里稳如泰山（不提前炸），癌细胞内自动解锁（精准释放）细胞毒性载荷微型 “毒药包” 毒性强（IC50 达纳摩尔级），偶联后活性不变（药效不打折）如果说 ADC 是 “顺丰重卡”（抗体分子量大，穿透实体瘤有局限），PDC 就是 “外卖小哥”。ADC 依赖抗体的特异性识别与内吞，PDC 依赖多肽 - 受体结合及小分子渗透，各有优劣体型小：分子量＜3kD，比抗体小 100 倍，更易抵达实体瘤核心；速度快：受体介导内吞，被癌细胞主动 “请” 进去，递送效率翻倍；低风险：免疫原性较低（多肽分子量小，人源化程度高），过敏反应风险理论上低于抗体类药物）！二、四步绝杀癌细胞！PDC 的 “精准打击” 全过程精准认亲：多肽与肿瘤细胞表面靶点 “锁钥结合”，比如 RGD 肽专门盯紧整合素 αvβ3（肺癌、乳腺癌高表达），正常细胞完全不识别；主动投怀：肿瘤细胞以为是 “营养物质”，通过内吞作用把 PDC 全套吞进胞内；智能解锁：癌细胞内酸性环境或特定酶（如组织蛋白酶 B）触发连接子裂解，比如 Val-Cit 连接子瞬间 “剪开”；定点爆破：载荷释放后，要么破坏癌细胞 DNA（如 SN38），要么抑制微管形成（如 MMAE），癌细胞在 24-48 小时内凋亡～对比维度 PDC 疗法 ADC 疗法传统化疗肿瘤穿透性强，易达实体瘤核心（小分子易渗透）较好，已获批实体瘤适应症无靶向，全身扩散（乱杀一通）脱靶毒性极低，正常细胞零损伤（靶点精准）中等，偶发脱靶反应（抗体可能认错）极高，杀敌一千自损八百（不分敌我）生产成本低，多肽合成易规模化（结构简单）高，抗体生产工艺复杂（制备难度大）低，但疗效差（无技术门槛）耐药风险较低，可多靶点组合设计（灵活搭配）中高，单靶点易耐药（靶点突变即失效）极高，快速产生耐药性（癌细胞适应快）临床获批数量无现役上市药物（1 款曾获批后撤市）多（全球超 19 款获批）多，但逐渐被靶向药替代三、近3年爆火！4大核心靶点 + 明星药物，国内外企业竞逐赛道靶点选对，成功一半！以下核心管线状态基于公开数据库（截至 2026 年 5 月），覆盖肿瘤、自身免疫病、骨科等多个领域，国内企业凭借差异化布局实现弯道超车： BDCA2 靶点：科兴制药自主研发的 GB19 注射液（PDC 类药物），靶向浆细胞样树突状细胞表面的 BDCA2 靶点，2026 年 3 月已获 NMPA 及 FDA 临床试验批准，目前处于 I 期临床阶段，有望为红斑狼疮患者提供新的治疗选择，是国内首个实现 PDC “中美双报” 的自身免疫病管线。 Nectin-4 靶点：Bicycle Therapeutics 的 BT8009（属双环肽 - 毒素偶联物，广义归为 PDC 范畴），靶向实体瘤高表达的 Nectin-4 受体，目前临床进展领先 ——I/II 期 Duravelo-1 试验（NCT04561362）的小样本队列（8 例可评估患者）中，尿路上皮癌患者客观缓解率（ORR）达 50%（4/8）、疾病控制率（DCR）75%（6/8），对 ADC 耐药患者仍有疗效；2024 年已启动 Phase 2/3 确证性试验 Duravelo-2（NCT06225596），加速推进大样本验证。 EphA2 靶点：Bicycle Therapeutics 的 BT5528（国际非专利名称（INN）为 nuzefatide pevedotin，研发代号；NCT04180371），靶向胰腺癌、卵巢癌等实体瘤高表达的 EphA2 受体，目前处于 I/II 期临床阶段 ——Phase 1 剂量递增已完成，推荐剂量（RP2D）下 15 例可评估患者中，ORR 6.7%（1/15）、疾病控制率（DCR）20.0%（3/15）；联合 nivolumab 的队列中，EphA2 阳性尿路上皮癌患者 ORR 提升至 40%（4/10，AACR 2026 数据），安全性总体可控但需关注血液学毒性（22.2% 患者出现≥3 级中性粒细胞减少）。 SORT1 靶点：阿斯利康 TH1902 是针对三阴性乳腺癌的 PDC 候选药物，靶向 SORT1 受体，目前处于临床前研究阶段，基于 xenograft 小鼠模型的实验数据显示出良好的靶向性和抗肿瘤活性，有望解决三阴性乳腺癌化疗耐药的临床痛点。深度拆解：科兴 GB19 为何能实现 “中美双报”？靶点稀缺性：BDCA2 仅在浆细胞样树突状细胞表达，正常细胞几乎不表达，脱靶毒性趋近于零；多肽优化术：采用环化 + N - 甲基化双重修饰，血清稳定性提升 5 倍，半衰期延长至 24 小时（避免快速被代谢）；临床价值明确：临床前研究显示对 BDCA2 靶点抑制时间维持超 90 天，可有效抑制 I 型干扰素释放，直击红斑狼疮的核心发病机制，填补临床未满足需求。国外标杆案例：Bicycle BT8009 的临床突破技术特色：采用双环肽（bicyclic peptide）载体，兼具高亲和力与高稳定性，相比传统多肽更易穿透肿瘤微环境；靶向优势：Nectin-4 在尿路上皮癌、乳腺癌等多种实体瘤中高表达，且与肿瘤侵袭转移相关，是理想的治疗靶点；临床推进：从 Phase 1 到 Phase 2/3 仅用 4 年时间，凭借小样本队列的高 ORR 数据快速获得监管认可，彰显 PDC 药物 “临床转化快” 的核心优势。国外标杆案例：Bicycle BT5528 的临床进展命名规范：2026 年 4 月 Bicycle Therapeutics 公布其国际非专利名称（INN）为 “nuzefatide pevedotin”，为后续全球化商业化布局奠定基础；联合用药潜力：单药疗效有限，但与 PD-1 抑制剂 nivolumab 联用后疗效显著提升，验证了 PDC + 免疫治疗的协同机制，为实体瘤联合治疗提供新范式；适应症拓展：目前重点探索胰腺癌、卵巢癌等难治性实体瘤，这些领域化疗效果差、靶向药物稀缺，市场需求迫切。下期预告这个主题的内容较多，分为多期发布，敬请期待！免责声明：本文数据来源于公开学术文献、监管文件及企业公告，部分未发表数据来自学术会议摘要，可能存在后续调整。文中观点不代表本平台立场，不构成任何疾病诊断、治疗方案或投资建议。医疗健康决策请咨询专业医生，投资行为请独立判断并承担风险。内容仅供学习交流，如有侵权请联系删除。原创日更｜关注小编 --获取生物制药行业的前沿动态-- --感谢点赞、关注、转发-- 点击上方关注小编

抗体药物偶联物多肽偶联药物临床结果

2026-04-30

·知乎专栏

行业研究 | 全球重要环肽管线资产

｜中肽生化内容团队编辑环肽药物作为一类介于传统小分子和生物大分子之间的特殊分子形态，近年来在全球创新药研发管线中的占比稳步提升。通过引入环化结构，这类药物在保留多肽高特异性和高亲和力的基础上，显著提高了对蛋白酶的稳定性和结构预限制性，从而在调节蛋白质相互作用（PPI）等难成药靶点上展现出独特的优势。随着icotrokinra的获批，环肽技术在改善药物代谢动力学性质、探索非注射给药途径等方面的实际潜力得到了更多实证。从全球环肽资产的全景分布来看，目前的研发重点正从天然产物的简单修饰转向基于噬菌体展示（phage display）技术和de novo设计的系统化开发。在研管线广泛覆盖了自身免疫、肿瘤、代谢性疾病以及抗感染等多个核心领域，体现出差异化的技术路径和商业价值。通过梳理当前的管线梯队，可以客观观察到不同研发平台在分子量控制、跨膜渗透性优化以及长效化修饰等关键指标上的真实进展，进而评估该类资产在未来医药市场中的竞争地位。1. MK‑0616（Enlicitide）图片来源：Wikipedia开发商：默沙东环肽结构特征Enlicitide（MK‑0616）是一个围绕口服吸收目标进行深度工程化改造的宏环肽，而且是非常独特的三环肽，其结构特征体现为多层次化学设计的叠加，包含如下特征：✔ 三环肽✔ 吲哚结构✔ (S)-2-甲基脯氨酸✔ 氟取代✔ 季胺结构✔ 特殊的合环结构适应症与临床✔ 高胆固醇血症（Hypercholesterolemia）临床研究：CORALreef Lipids（NCT05952856，III期）这项三期研究受试者为高胆固醇血症成年人，研究目的为评估 Enlicitide 在此人群中的 LDL‑C 降幅和安全性。✔ 杂合子家族性高胆固醇血症（Heterozygous Familial Hypercholesterolemia, HeFH）临床研究：CORALreef HeFH（NCT05952869，III期）✔ 在既有降脂治疗基础上仍需额外降低 LDL‑C 的成人临床研究：CORALreef Add‑On（NCT06450366，III期）研究对象包括正在使用他汀或其他降脂药（ezetimibe、bempedoic acid）的成年人，专门针对仍需额外降低 LDL‑C 的患者所进行的加用研究✔ 具有动脉粥样硬化性心血管事件风险的成年人（ASCVD‑risk adults）临床研究：CORALreef Outcomes（NCT06008756，III期）机理MK‑0616 的作用机理与已上市的抗体类 PCSK9 抑制剂一致，其分子能够直接与 PCSK9 的 LDL（低密度脂蛋白）受体结合域发生结合，从而阻断 PCSK9 与 LDL 受体之间的相互作用。这种结合可使 PCSK9 失去降解 LDL 受体的能力，使更多 LDL 受体得以在肝细胞表面存留并回收 LDL‑C，最终导致血浆 LDL‑C 水平下降。递送方式：口服从药代动力学层面，enlicitide已有早期临床试验提供了直接证据：在健康受试者中，口服给予 10–300 mg 的 MK‑0616 能使血浆游离 PCSK9 水平降低超过 93%。MK‑0616 的注册路径全部基于口服给药。所有临床试验采用的是 Enlicitide Decanoate 的口服片剂。这使得 MK‑0616 成为迄今推进最靠前的口服 PCSK9 抑制剂。相较于注射型 PCSK9 抗体治疗方式，口服剂型拥有更高的依从性、更低的使用门槛，并有可能将 PCSK9 抑制剂从特殊用药带入初级干预药物的层级。开发意义从行业视角看，Enlicitide 是第一个真正进入注册性阶段的口服宏环肽药物，也是第一个有机会实现口服 PCSK9 抑制的品种。这意味着大尺寸蛋白–蛋白相互作用靶点首次能够通过口服肽类药物进行调控。更重要的是，三个 LDL‑C 关键试验的成功完成与大型心血管终点试验的稳步推进共同构成了一个即将进入申报期的证据体系，使其成为未来可能改变降脂治疗模式的战略级药物。相关公开资料显示，MK‑0616 进入 Phase 3 后的进展顺利，并已被业内视为下一阶段监管申报的候选品种。2. BT5528开发商：Bicycle Therapeutics环肽结构特征BT5528 是Bicycle Therapeutics 所开发的 Bicycle® Toxin Conjugate（BTC），其本质可视为PDC（Peptide-Drug Conjugate, 多肽药物偶联物）。其受体识别模块为一个 bicyclic peptide（双环肽），能够特异性结合 EphA2，并与细胞毒素 monomethyl auristatin E（MMAE）通过可切割连接子（protease‑cleavable linker）连接。BT5528 的结构与传统 PDC 最大的不同，在于它的 “P”与“D”两部分都是肽类结构。传统 PDC 通常由一段识别肽连接一个小分子毒素，而在 BT5528 中，靶向部分本身是一个双环肽（bicyclic peptide），而毒素 MMAE 也是一个肽源性的细胞毒素。再加上中间的多肽 spacer 和可切割肽链连接子，BT5528 呈现出的是肽‑肽偶联的整体架构，而不是传统的肽‑小分子偶联。✔ 双环肽（bicyclic peptide）：靶向 EphA2✔ MMAE（monomethyl auristatin E）细胞毒素：作为载荷，与肽偶联✔ 蛋白酶可切割连接子（protease‑cleavable peptide linker）：连接肽与 MMAE 的关键结构✔ Spacer：β‑Ala‑Sar10多肽，环肽与连接子之间，用于结构衔接✔ EphA2 结合模块：双环肽本体用于识别 EphA2 高表达肿瘤环肽特征：通过1,3,5-triazinane (1,3,5-三氮杂环己烷)，与直链肽前体上的三个半胱氨酸类似物Cys((CH2)2COOH)侧链的羧基结合，从而形成双宏环的化学结构。适应症与临床✔ EphA2 高表达的晚期实体瘤临床研究：BT5528‑100（NCT04180371，I/II 期），研究对象为EphA2 高表达的既往已知类型的晚期实体瘤，包括卵巢癌、尿路/膀胱癌、非小细胞肺癌、头颈癌、三阴性乳腺癌、胃/上消化道癌等多类实体瘤。机理BT5528属于一种 Bicycle Toxin Conjugate（BTC）。其双环肽部分识别并结合肿瘤细胞表面的 EphA2。EphA2 是多种实体瘤中高表达的细胞表面受体。双环肽结构通过其特定的空间构象与 EphA2 的细胞外结构域发生高亲和力结合，使 BT5528 能够在 EphA2 高表达的肿瘤组织中实现选择性富集。当双环肽将 BT5528 锚定于 EphA2 阳性肿瘤细胞后，连接子在肿瘤环境中被蛋白酶切割，从而释放细胞毒素 MMAE ，MMAE 进入细胞后作用于微管系统，从而杀伤肿瘤细胞并递送方式BT5528 的给药方式在为静脉注射（IV）。NCT04180371 试验的给药频率为每周一次（QW）或每两周一次（Q2W）。开发意义BT5528 通过双环肽结构实现对 EphA2 的高亲和力识别，并以可切割连接子将肽源性细胞毒素 MMAE 精准递送至肿瘤细胞。其早期临床研究显示，BT5528 在多种 EphA2 高表达的晚期实体瘤中展现了可管理的安全性和初步抗肿瘤活性。这些结果为 Bicycle Toxin Conjugate（BTC）这一新型分子形式提供了临床可行性的初步验证，体现出以合成双环肽为基础构建偶联毒素药物的潜在发展价值。3. BT8009 (Zelenectide pevedotin)图片来源：Bicycle Therapeutics开发商：Bicycle Therapeutics环肽结构特征同BT5528一样，BT8009 (Zelenectide pevedotin) 同样属于 Bicycle Therapeutics 的 Bicycle Toxin Conjugate（BTC），其靶向结构是一个高度选择性的双环肽（bicyclic peptide），用于结合 Nectin‑4（肿瘤表面黏附分子）。其机构包括如下模块：✔ 双环肽（bicyclic peptide），结合Nectin-4;✔ 用于连接肽与毒素的可切割连接子（val‑cit‑PABC）✔ 细胞毒素 MMAE（monomethyl auristatin E）适应症与临床✔ Nectin‑4 高表达的晚期实体瘤临床研究：BT8009‑100（NCT04561362，I/II 期）针对Nectin‑4 表达相关的晚期实体瘤，包括尿路上皮癌、胰腺癌、乳腺癌、非小细胞肺癌、胃癌、食管癌、头颈癌、卵巢癌等。✔ 局部晚期或转移性尿路上皮癌（la/mUC）临床研究：Duravelo‑2（NCT06225596，II/III 期），针对局部晚期或转移性尿路上皮癌的注册性研究，并作为化疗对照的比较组之一。✔ 转移性尿路上皮癌（单药与联合 pembrolizumab）临床研究：Duravelo‑1（NCT04561362 的扩展部分）机理BT8009 的受体靶向部分是一个双环肽，可选择性结合 Nectin‑4。Nectin‑4 是一种位于细胞表面的黏附分子，它在多种肿瘤组织中常见高表达，包括尿路上皮癌、肺癌、上消化道肿瘤、卵巢癌、乳腺癌以及头颈部肿瘤等。BT8009与Nectine-4结合后，可切割连接子在肿瘤微环境中被特定蛋白酶分解，释放出毒素MMAE（monomethyl auristatin E），通过抑制微管使细胞停止分裂并最终死亡。递送方式：静脉注射静脉给药，包括每周一次、每两周一次或 21 天周期的 D1+D8 给药方案。开发意义BT8009 展示了 Bicycle Toxin Conjugate（BTC）技术在 Nectin‑4 靶向肿瘤中的应用潜力，其双环肽结构赋予药物小分子级别的组织穿透性与高度选择性的肿瘤富集能力。早期临床数据显示，BT8009 在转移性尿路上皮癌中展现出明确的抗肿瘤活性和良好耐受性，部分研究观察到高达 45% 的客观缓解率（ORR）。基于这些结果，FDA 已与开发方就其 II/III 期注册性研究达成一致，使 BT8009 成为首批可能进入加速审批路径的 BTC 类候选药物之一。4. BT7480图片来源：Biopharma PEG图片来源：WO2025125648开发商：Bicycle Therapeutics环肽结构特征BT7480 是一种由三个双环肽（bicyclic peptides）组成的分子，包括：✔ 一个双环肽靶向 Nectin‑4✔ 两个双环肽靶向 CD137（4‑1BB）（免疫细胞表面共刺激受体）三个双环肽通过一个三臂 PEG₃（branched trimeric PEG）连接子进行连接，是一个完全化学合成的多肽免疫激动剂结构。适应症与临床✔ Nectin‑4 表达相关的晚期实体瘤临床研究：NCT05163041（I/II期）研究的实体瘤包括非小细胞肺癌、尿路上皮癌、头颈鳞癌、宫颈癌、食管癌、胃癌、卵巢癌、乳腺癌等多种 Nectin‑4 阳性肿瘤机理BT7480 的出现，为多肽药物在“结构复杂性”与“机制功能性”的融合设计提供了一个清晰范式。它既不同于传统意义上仅承担识别功能的环肽，也不同于体积更大、构象受限的融合蛋白或抗体药物。BT7480 以完全化学合成的方式，将三个功能精确分区的双环肽结构域组合成一个整体分子，通过结构域分离的策略同时实现肿瘤靶向与免疫激活两个目的，其结构布局在功能逻辑上已接近、甚至重构了双抗式（bispecific）的作用模式。在分子层面，BT7480 由一个靶向 Nectin‑4 的双环肽结构域和两个靶向 CD137 的双环肽结构域构成。Nectin‑4 是多种实体瘤中高度表达的黏附分子，而 CD137（4‑1BB）则是活化 T 细胞与 NK 细胞表面的关键共刺激受体。BT7480 的设计使其能够在肿瘤细胞（Nectin‑4）与免疫细胞（CD137）之间实现空间上的共缀合（co‑ligation），从而将免疫激活信号精准定位在肿瘤局部。这种设计与传统依赖单一肽段承担全部功能的 GLP‑1/GIP 类多受体激动剂不同，而是通过物理结构域分离，使每一部分均承担清晰、独立且可控的药理任务。围绕 CD137 的激动策略，是 BT7480 的另一核心价值。CD137 作为 TNF（肿瘤坏死因子）受体家族成员，其激活需要聚合，但以往的 CD137 激动抗体由于系统性激活导致的肝毒性，长期阻碍了临床推进。BT7480 以小分子双环肽为基础，通过噬菌体展示筛选、亲和力成熟与化学优化获得能够结合 CD137 的环肽模板，再与识别 Nectin‑4 的环肽通过三臂连接子拼接，使 CD137 的聚合仅在肿瘤部位被触发，实现了肿瘤局部免疫激活而避免系统性副作用。最终形成的 BT7480 分子，实现了“靶向 + 激活”功能的物理隔离与空间耦合，为 CD137 激动剂的发展提供了新的结构途径。递送方式：静脉注射开发意义BT7480 代表了 Bicycle Therapeutics 的肿瘤定向免疫激动剂（Bicycle TICA®）平台首次进入人体研究，利用三个双环肽同时连接肿瘤细胞的 Nectin‑4 与免疫细胞的 CD137，实现精准的局部免疫激活机制。在早期临床结果中，BT7480 显示出良好的耐受性与初步抗肿瘤活性，包括未确认的部分缓解（PR）与多例超过 8 个月的长期稳定疾病（SD）。由于其机制与结构均完全不同于传统抗体和 ADC，BT7480 被视为 BTC / TICA 类药物在实体瘤免疫激活方向的重要验证性项目，并已进入持续推进的临床阶段。5. PL8177开发商：Palatin Technologies多肽结构特征PL8177 是7个氨基酸组成的环肽，其中5个氨基酸残基参加了环肽结构的构成，Glu侧链的羧基与Dap (Diaminopropionic acid) 侧链的氨基形成了侧链-侧链酰胺环化。适应症与临床✔ 活动性溃疡性结肠炎（Active Ulcerative Colitis, UC）临床研究：NCT05466890 (IIa期)，双盲、随机、安慰剂对照试验，采用口服结肠递送方案，在轻中度活动性溃疡性结肠炎患者中进行 8 周治疗，评估其安全性、PK/PD、肠黏膜愈合与临床缓解效果。机理PL8177 的作用机制属于对 melanocortin‑1 受体（MC1R）的选择性激动。在结肠局部释放后，MC1R 激动所触发的生物学效应能够调节黏膜免疫状态，使局部炎症从“损伤模式”向“修复模式”转化，并推动炎症分辨过程，而不是像传统免疫抑制剂那样抑制免疫反应本身。这一机制的实现依赖其结肠定向递送体系：Phase 1 研究显示口服 PL8177 能够在结肠局部达到有效暴露，同时几乎不进入血液循环，从而以最小系统暴露的方式降低全身不良反应风险，实现了以局部免疫调节为核心的治疗策略。递送方式：口服PL8177是一种选择性 melanocortin‑1 receptor（MC1R）激动剂，归类为 melanocortin 多肽类药物（melanocortin receptor agonist）。它采用口服结肠递送（oral colon‑delivered）体系，定向结肠递送，减少系统暴露，用于在局部发挥抗炎与组织修复相关作用，而非免疫抑制。开发意义PL8177 展示了 MC1R 激动在肠道局部炎症疾病中的新型应用路径，通过结肠定向释放实现作用部位与系统暴露的分离，从而减少传统免疫抑制剂常见的安全性问题。在活动性 UC 的 Phase 2a 研究中，PL8177 显示出显著的临床缓解、黏膜改善与优异安全性，公开数据中无治疗相关不良事件。这些结果使 PL8177 成为 MC1R 口服治疗在肠道炎症疾病领域的首个验证性成果，并促使开发者已开启与大型药企的许可与合作洽谈。6. Certepetide（CEND-1）开发商：Lisata Therapeutics多肽结构特征Certepetide 来源于 iRGD（CRGDKGPDC）序列，是一个9个氨基酸组成的环状多肽。其结构特征为通过两个半胱氨酸残基形成二硫键，构建稳定的环状构象。该序列包含典型的 RGD 基序，可与整合素（αvβ3/αvβ5）结合，并在蛋白酶裂解后暴露 C-end Rule（CendR）基序，从而获得与 neuropilin-1（NRP-1）结合的能力。这种结构赋予其“先结合整合素、再激活组织穿透通路”的双阶段功能特征。适应症与临床✔ 胰腺导管腺癌（Pancreatic Ductal Adenocarcinoma, PDAC）临床研究：ASCEND（II期，NCT05042128），在一线化疗基础上联合 certepetide，评估客观缓解率、无进展生存期等指标。已披露数据中 ORR 约45%，对照组约19%，mPFS 约7.5个月，对照组约4.7个月。✔ 胆管癌（Cholangiocarcinoma）临床研究：（NCT05628064，II期），已获得孤儿药资格认定，正在推进，用于评估其在胆道系统肿瘤中的增敏作用。✔ 晚期实体瘤临床研究：NCT03517176 （Phase 1b/2），评估 certepetide 联合化疗在晚期实体瘤中的安全性与初步疗效；NCT04958811（Phase 1b/2），在多种晚期实体瘤中评估其作为递送增强剂的作用。机理Certepetide 的作用机制属于肿瘤组织穿透增强（tumor penetration enhancer）。Certepetide 首先通过其序列中的 RGD 结构与肿瘤血管和肿瘤细胞表面的αv 整合素结合。结合后，该多肽在肿瘤微环境中被蛋白酶切割，使其C端暴露出能够与 neuropilin-1 结合的结构，从而激活一种内吞-跨细胞运输通路。该通路能够在肿瘤组织中形成类似通道的结构，显著提高共给药药物（如化疗药物）在肿瘤内部的分布和渗透深度。其核心作用并不直接杀伤肿瘤细胞，而是通过改变药物在肿瘤组织内的空间分布，提高局部有效暴露，从而增强已有治疗方案的疗效。递送方式：静脉注射Certepetide 作为辅助性多肽药物，与化疗或其他抗肿瘤药物联合使用，通过静脉给药实现全身分布，但其功能主要在肿瘤局部发挥。其作用依赖肿瘤特异性的整合素表达和NRP-1通路激活，因此具有一定的组织选择性。开发意义Certepetide 提供了一种区别于传统靶向治疗与细胞毒药物的开发路径，其核心在于通过调控肿瘤组织结构与药物分布，提高既有疗法的有效性。该策略针对实体瘤中普遍存在的药物渗透受限问题，尤其在胰腺癌等高基质、低血供肿瘤中具有明确理论基础。已有 II 期数据显示其在联合治疗中可提高缓解率并延长无进展生存期，提示该类递送增强型多肽具有成为肿瘤治疗新辅助模块的潜力。同时，该机制具有与多种治疗手段（化疗、放疗、免疫治疗）组合的兼容性，为后续联合策略提供了空间。7. Balixafortide （POL6326）开发商：Spexis（原 Polyphor）多肽结构特征Balixafortide的化学结构非常特殊，它由16个氨基酸残基组成，通过Cys2和Cys9的侧链巯基形成二硫键，与此同时，其[Ala1-Arg7]-的部分和[His16-Tyr8]的部分，通过N对N, C对C的方式进行对接环化，从而产生了肼（红色部分）和1,2-diketone（蓝色部分）的特殊结构，并赋予Balixafortide极为特殊的双环结构。适应症与临床✔ 转移性胰腺导管腺癌（PDAC）临床研究：NCT06981806（I期），联合 cosibelimab（PD-L1 抗体），用于标准治疗失败后的转移性 PDAC。计划入组 24 例，主要目标为确定最大耐受剂量（MTD）及推荐 II 期剂量（RP2D）。机理Balixafortide 的作用机制为 CXCR4 受体拮抗。CXCR4 是肿瘤细胞与肿瘤微环境中重要的趋化因子受体，与其配体 CXCL12（SDF-1）共同参与肿瘤细胞迁移、免疫逃逸及肿瘤微环境重塑。Balixafortide 通过与 CXCR4 结合，阻断 CXCL12-CXCR4 信号轴，从而干扰肿瘤细胞向转移部位的趋化迁移，并影响肿瘤相关免疫细胞的募集与分布。在免疫治疗联合策略中，该机制还可能通过改变肿瘤微环境中免疫抑制状态，提高免疫细胞浸润，从而增强免疫检查点抑制剂的疗效。递送方式：静脉注射开发意义Balixafortide 代表了一类针对肿瘤微环境趋化信号通路的多肽药物，其开发重点在于调控肿瘤细胞迁移及免疫微环境，而非直接细胞毒作用。CXCR4 作为肿瘤转移和免疫抑制的重要节点，在多种实体瘤中具有明确生物学基础。尽管其在乳腺癌 III 期研究中未取得阳性结果，但后续在胰腺癌等高度免疫抑制肿瘤中的早期探索仍在进行。当前可见临床活动主要集中在小规模早期研究，提示该项目仍处于机制验证与适应症再定位阶段。8. Rusfertide（PTG-300 / TAK-121）开发商： Protagonist Therapeutics / 武田制药多肽结构特征Rusfertide 是17个氨基酸残基组成的环肽，其中Cys6-Cys16之间形成二硫键。Rusfertide的N端经过了异戊酰基修饰。其Lys8的侧链还通过gama glutamic acid进行了棕榈酸（16碳脂肪酸）的脂化修饰。适应症与临床✔ 真性红细胞增多症（Polycythemia Vera, PV）临床研究：VERIFY（NCT05210790，III期）：rusfertide 联合标准治疗使临床应答率超过安慰剂组两倍；Takeda 公布的数据为 77.0% vs 32.9%，并达到主要终点和全部四个关键次要终点；THRIVE（NCT06033586，III期）：是一项开放标签长期延长期研究，用于评估 rusfertide 的长期安全性和疗效持续性。✔ 当前进展：rusfertide 的 NDA 已被 FDA 受理并授予 Priority Review，PDUFA 目标日期位于 2026 年第三季度。机理Rusfertide 的作用机制属于 hepcidin 模拟。其核心在于模拟内源性 hepcidin 对 ferroportin 的调控作用，降低铁从肠道和储存组织向血液循环的输出，从而减少可用于红细胞生成的铁供给，最终抑制过度红细胞生成并维持血细胞比容控制。该机制调控的是铁代谢上游环节，而不是直接抑制骨髓细胞增殖。递送方式：皮下注射开发意义Rusfertide 是当前最接近上市的环肽项目之一，其意义首先在于它验证了环肽可以作为全身性铁代谢调节药物进入后期临床并冲击上市。在真性红细胞增多症中，传统管理长期依赖放血和细胞减灭治疗，而 rusfertide 通过 hepcidin 模拟这一全新机制，从铁供给端限制红细胞生成，为疾病控制提供了新的治疗路径。

2026-04-30

·BioSpace

Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2026 Financial Results

Presentations at AACR Annual Meeting 2026 underscore significant opportunities for nuzefatide pevedotin in EphA2 expressing cancers, including pancreatic cancer Human imaging data provides further evidence of the potential of EphA2 as a novel cancer target and the positive properties of Bicycle ® radioligand molecules for radiopharmaceutical use Initial dose selection data from Duravelo-2 trial evaluating zelenectide pevedotin plus pembrolizumab in metastatic urothelial cancer to be presented at 2026 ASCO Annual Meeting Cash and cash equivalents of $559.5 million as of March 31, 2026, with expected cash runway into 2030 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 reported financial results for the first quarter ended March 31, 2026, and provided recent corporate updates. “The data we reported in the first quarter continues to provide further validation of the potential of our Bicycle technology to deliver oncology therapeutics with improved benefit/risk profiles compared to existing modalities,” said Bicycle CEO Kevin Lee, Ph.D. “We are excited by the emerging pro our EphA2 drug conjugate, nuzefatide pevedotin, which we have now tested in over 150 patients to date, both as a monotherapy and in combination with a checkpoint inhibitor. Nuzefatide has been shown to be generally well tolerated at clinically active doses, in contrast to previous attempts to drug this target with other modalities. We believe these data, together with those presented at AACR, provide a strong rationale for advancing the development of nuzefatide in pancreatic cancer, and we are pleased to have recently dosed our first patient in our Phase 2 trial. In addition to this, the preliminary data we have reported from our Duravelo-2 program demonstrate zelenectide pevedotin to also be clinically active with a differentiated safety profile, providing convincing evidence that Bicycle drug conjugates may exhibit a fundamentally different tolerability pro that seen with antibody-based approaches, and support our mission of helping patients not only to live longer but also to live well.” Dr. Lee added: “Following a strategic reprioritization in the first quarter, we are converting the Duravelo-2 trial into a randomized Phase 2 trial, allowing us to focus our internal resources on our emerging pipeline of next-generation therapeutics, including nuzefatide and Bicycle-based radiotherapeutics and imaging agents. We look forward to presenting initial dose selection data from our Duravelo-2 trial at the upcoming 2026 ASCO Annual Meeting and will continue to evaluate the best path for this program as the data continues to mature.” First Quarter 2026 and Recent Events Data presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 demonstrates significant opportunities for nuzefatide pevedotin (nuzefatide), formerly BT5528, a potentially first-in-class EphA2 targeting Bicycle ® Drug Conjugate (BDC ® ), in EphA2 expressing cancers. Nuzefatide Phase 1/2 data show a differentiated safety pro combination with nivolumab in metastatic urothelial cancer (mUC) patients as well as promising anti-tumor activity. As of the February 9, 2026 data cutoff, results from the Phase 1/2 trial evaluating nuzefatide 6.5mg/m 2 once every two weeks (Q2W) plus nivolumab 480mg once every four weeks (Q4W) in 14 patients with mUC who had previously progressed on a checkpoint inhibitor (10 while on enfortumab vedotin) showed: 40% confirmed overall response rate (ORR) (4/10) among patients with EphA2+ tumors and 100% confirmed ORR (3/3) among patients with EphA2+ tumors that were monomethyl auristatin E (MMAE)-naïve. Patients who achieved a partial response (PR) or at least 16 weeks of stable disease (SD) were on treatment for a minimum of 56 weeks and most continued on treatment at the time of the data cut-off. Nuzefatide in combination with nivolumab was generally well tolerated with no Grade ≥3 treatment-related adverse events (TRAEs) of clinical interest and no TRAEs of hemorrhage observed. Only one dose-limiting toxicity of Grade 3 fatigue that lasted for five days was reported and improved to Grade 1 without dose reduction. Preclinical assessment of nuzefatide anti-tumor activity in patient-derived xenograft (PDX) models of pancreatic ductal adenocarcinoma (PDAC). Expression of EphA2 was found in all 16 PDAC PDX models. Of the 14 PDAC PDX models assessed for anti-tumor activity, 10 models were sensitive to nuzefatide, six of which showed high sensitivity. Preclinical assessment of nuzefatide anti-tumor activity in cell-line-derived xenograft (CDX) models of head and neck squamous cell carcinoma (HNSCC). Nuzefatide demonstrated potent preclinical anti-tumor activity in EphA2-expressing CDX models of HNSCC. Altogether, Bicycle Therapeutics believes that these data highlight significant opportunities for nuzefatide in EphA2 expressing cancers, including pancreatic cancer. In March 2026, Bicycle Therapeutics began enrolling a Phase 2 clinical trial to evaluate efficacy, safety, and pharmacokinetics of nuzefatide in adult patients with recurrent PDAC, and the first patient was successfully dosed in April 2026. Bicycle Therapeutics has determined 8mg/m 2 Q2W as the preferred dose for the trial. Additional human imaging data of a Bicycle ® Imaging Agent (BIA) targeting EphA2 in patients with PDAC presented at AACR Annual Meeting 2026. The German Cancer Consortium (DKTK), part of a cooperative network with the German Cancer Research Center (DKFZ), presented human imaging data conducted with a Bicycle molecule targeting EphA2 labelled with gallium-68 (EphA2 BIA). Seven patients with histologically confirmed PDAC underwent PET/CT imaging up to three hours post injection of the EphA2 BIA. Data demonstrated rapid tumor uptake in six out of seven patients with excretion primarily via the kidneys. EphA2 BIA PET imaging successfully detected multiple liver, bone, lymph node, and peritoneal metastases. These data are representative of the results seen in 15 out of 18 patients with PDAC who have undergone EphA2 BIA imaging to date. Bicycle Therapeutics believes these data validate the potential of EphA2 as a novel target in the treatment of cancer, demonstrate the translatability of preclinical data and highlight the potential of Bicycle ® molecules for targeted radioligand therapies and radiopharmaceutical imaging. Promising Duravelo-2 data and multiple potential regulatory pathways provide a range of options for a Phase 3 trial and potential commercialization of zelenectide pevedotin (zelenectide) in mUC. Initial dose selection data from the Duravelo-2 trial demonstrate response rates comparable to those published for existing standards of care, with physician assessed ORR of 65%, blinded independent central review (BICR) confirmed ORR of 58% at the 27-week cutoff and a differentiated safety profile. Subsequent to the 27-week cutoff, an additional confirmed BICR response was observed, which would result in an ORR of 62%. Zelenectide at 6mg/m 2 two weeks on, one week off demonstrated a differentiated safety pro only one patient discontinuing therapy due to a TRAE at the 27-week cutoff. While Bicycle Therapeutics evaluates preliminary regulatory feedback from the European Medicines Agency, U.S. Food and Drug Administration (FDA), and Medicines and Healthcare products Regulatory Agency, and the potential paths for this program, the company is converting the ongoing Duravelo-2 trial to a randomized Phase 2 trial and deprioritized the program for internal development. Bicycle Therapeutics will present initial Duravelo-2 dose selection data at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29-June 2 in Chicago. Strategic reprioritization focuses on promising pipeline of next-generation therapeutics. In March 2026, Bicycle Therapeutics initiated a strategic reprioritization in order to focus its resources on its promising pipeline of next-generation therapeutics, including nuzefatide, as well as its emerging Bicycle conjugate pipeline, including BRCs. As part of the reprioritization, Bicycle Therapeutics seeks to discontinue the Phase 1/2 Duravelo-3 trial for zelenectide in NECTIN4-amplified breast cancer and the Phase 1/2 Duravelo-4 trial for zelenectide in NECTIN4-amplified non-small cell lung cancer. Enrollment for these trials is closed, and patients currently enrolled will complete their course of treatment. In addition, Bicycle Therapeutics announced a workforce reduction pursuant to which it expects to reduce its workforce by approximately 30%. Anticipated annual operational savings related to the workforce reduction and strategic reprioritization are expected to reduce annual operating expenses by approximately 50% based on the company’s current plans. These actions are expected to extend Bicycle Therapeutics’ cash runway by approximately two years, into 2030. First Quarter 2026 Financial Results Cash and cash equivalents were $559.5 million as of March 31, 2026, compared to $628.1 million as of December 31, 2025. The decrease in cash and cash equivalents is primarily due to cash used in operations, including cash payments for clinical program activities. Collaboration revenue was $0.9 million for the three months ended March 31, 2026, compared to $10.0 million for the three months ended March 31, 2025. The decrease in collaboration revenue of $9.1 million was primarily due to the termination of our collaboration programs with Genentech and Novartis. Research and development (R&D) expenses were $48.9 million for the three months ended March 31, 2026, compared to $59.1 million for the three months ended March 31, 2025. The decrease in expense of $10.2 million was primarily due to decreased clinical program expenses for zelenectide and share-based compensation due to our workforce reduction, offset by lower U.K. R&D tax credits period over period. General and administrative (G&A) expenses were $17.5 million for the three months ended March 31, 2026, compared to $21.1 million for the three months ended March 31, 2025. The decrease in expense of $3.6 million was primarily due to decreased professional and consulting fees and decreased share-based compensation due to our workforce reduction. Net loss was $60.8 million, or $(0.87) basic and diluted net loss per share, for the three months ended March 31, 2026, compared to net loss of $60.8 million, or $(0.88) basic and diluted net loss per share, for the three months ended March 31, 2025. About Bicycle Therapeutics 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. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating nuzefatide pevedotin, formerly BT5528, a Bicycle ® Drug Conjugate (BDC ® ) targeting EphA2, a historically undruggable target; a pipeline of other bicycle-based conjugate molecules, including Bicycle ® Radioconjugates (BRC ® ) for radiopharmaceutical use; zelenectide pevedotin (formerly BT8009), a BDC ® targeting Nectin-4, a well-validated tumor antigen; BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist ® (Bicycle TICA ® ) targeting Nectin-4 and agonizing CD137; and, through various partnerships, is exploring the use of Bicycle ® technology to develop therapies for diseases in additional therapeutic areas. Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Lexington, Mass. For more information, visit bicycletherapeutics.com . Forward Looking Statements 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. Forward-looking statements in this press release include, but are not limited to, statements regarding: the potential therapeutic benefit of nuzefatide pevedotin, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, and the potential development of nuzefatide pevedotin in a number of cancers, including pancreatic cancer; the progress of Bicycle Therapeutics’ clinical trials, reporting data from Bicycle Therapeutics’ clinical trials, including for nuzefatide pevedotin, the timing of EphA2 human imaging data and updates on future clinical development plans for nuzefatide pevedotin; the potential of EphA2 as a novel cancer target and the positive properties of Bicycle ® radioligand molecules for radiopharmaceutical use; the development of the Bicycle ® radioligands pipeline, including BRCs and BIAs; the potential benefits of Bicycle Therapeutics’ strategic reprioritization, including the potential extension of financial runway; the workforce reduction and its impact on Bicycle Therapeutics’ expenditures; communications with and feedback from the FDA and other regulatory agencies including the potential for multiple regulatory pathways for zelenectide pevedotin in mUC; the existence of a range of options for a Phase 3 trial and potential commercialization of zelenectide pevedotin in mUC; Bicycle Therapeutics’ expected financial runway; and the use of Bicycle Therapeutics’ technology through various partnerships to develop therapies for diseases in additional therapeutic areas. Bicycle Therapeutics 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: the workforce reduction may take longer or result in more significant charges or cash expenditures than anticipated or otherwise negatively impact Bicycle Therapeutics’ and its business plans during and after the period during which the workforce reduction is being executed; uncertainties related to the benefits of the strategic reprioritization; uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle Therapeutics’ product candidates; the risk that Bicycle Therapeutics may not realize the intended benefits of its technology or partnerships; the risk that Bicycle Therapeutics may not achieve any of its clinical development strategies; timing of results from clinical trials; whether the outcomes of preclinical studies and prior clinical trials will be predictive of future clinical trial results; the risk that trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle Therapeutics’ product candidates; the risk that Bicycle Therapeutics’ projections regarding its expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Bicycle Therapeutics’ actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle Therapeutics’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 17, 2026, as well as in other filings Bicycle Therapeutics may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Bicycle Therapeutics expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Bicycle Therapeutics plc Condensed Consolidated Statements of Operations and Comprehensive Loss (In thousands, except share and per share data) (Unaudited) Three Months Ended March 31, 2026 2025 Collaboration revenue $ 887 $ 9,977 Operating expenses: Research and development 48,901 59,058 General and administrative 17,468 21,123 Total operating expenses 66,369 80,181 Loss from operations (65,482 ) (70,204 ) Other income (expense): Interest and other income 4,877 8,414 Interest expense (48 ) (51 ) Total other income, net 4,829 8,363 Net loss before income tax provision (60,653 ) (61,841 ) Provision for (benefit from) income taxes 172 (1,087 ) Net loss $ (60,825 ) $ (60,764 ) Net loss per share, basic and diluted $ (0.87 ) $ (0.88 ) Weighted average ordinary shares outstanding, basic and diluted 69,683,471 69,196,945 Balance Sheets Data (In thousands) (Unaudited) March 31, December 31, 2026 2025 Cash and cash equivalents $ 559,474 $ 628,110 Working capital 570,246 625,901 Total assets 652,396 717,597 Total shareholders’ equity 554,320 609,977 Contacts Investors: Matthew DeYoung Argot Partners ir@bicycletx.com 212-600-1902 Media: Argot Partners media@bicycletx.com

临床2期临床3期财报临床结果

100 项与 Zelenectide pevedotin 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
转移性尿路上皮癌	临床3期	美国	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	阿根廷	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	澳大利亚	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	比利时	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	巴西	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	加拿大	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	智利	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	法国	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	德国	Bicycle Therapeutics Plc	2024-01-24
转移性尿路上皮癌	临床3期	匈牙利	Bicycle Therapeutics Plc	2024-01-24

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04561362 (Duravelo-1, AACR2026)	临床1/2期	乳腺癌 NECTIN4 amplification	2,173	Zelenectide pevedotin	淵齋廠夢鹽積願廠積製(選獵襯醖壓製淵積蓋簾) = 鑰淵構繭鑰醖積餘醖鏇蓋遞艱範夢齋淵鑰網積 (窪獵鹽壓積壓鏇遞鏇鹹 )	积极	2026-04-22
NCT06840483 (Duravelo-3, ESMO2025)	临床2期	晚期乳腺癌 HR+ \| HER2- \| NECTIN4 amplified	66	Zelenectide pevedotin 6 mg/m (Triple-negative breast cancer + 1-3 prior lines of systemic therapy)	觸膚願壓積鑰襯餘鹽憲(範壓願壓顧淵醖觸構齋) = The most common treatment-related AEs (TRAEs) were hematological (neutropenia (60.6%); decreased platelets count (33.3%); decreased leukocytes count (33.3%)) and non-hematological (lanugo hair loss (60.6%); paronychia (42.4%); fatigue (36.4%)) events. Grade ≥3 TRAEs were observed in 24.2% of pts. One (6.7%) pt experienced a serious AE (neutropenia). 網繭廠膚鏇衊糧觸鏇醖 (選構觸夢鏇鑰簾齋襯簾 )	积极	2025-10-17
NCT04561362 (Duravelo-1, ESMO2025)	临床1/2期	非小细胞肺癌 NECTIN4 amplification	106	Zelenectide pevedotin (NECTIN4 amp)	憲蓋顧廠簾積獵繭鹹選(製壓襯構蓋憲繭願製選) = In TMAs, 20% of NSCLC samples showed NECTIN4 amp and 7.3% polysomy. NECTIN4 FISH correlated significantly with membranous protein expression (p<10, H-scores 130 and 0 with interquartile ranges 133 and 20 for NECTIN4-amp and non-amp, respectively), with RNA expression (p=0.001) and with WES-based copy number (p<0.001). In our own sequencing cohort, NECTIN4 amp was associated with KRAS mutations (p=0.041) and history of smoking (p=0.043), but not with overall survival, other therapeutically relevant genomic alteration and clinical parameters. In NECTIN4 amp tumors, expression of gene sets related to epithelial mesenchymal transition (EMT), inflammation and active immune response were significantly downregulated. Similarly, NECTIN4 expression correlated with ERBB2/ERBB3 expression, but inversely with expression of AXL, PDCD1 (PD1) & CTLA4 as well as estimated levels of infiltrating T cells and overall immune cell content. 鏇顧遞膚積膚夢願蓋遞 (製網淵遞鹹淵壓鏇製壓 )	积极	2025-10-17
NCT04561362 (Duravelo-1, ASCO2025)	临床1/2期	尿路上皮癌一线 Nectin-4	22	Zelenectide pevedotin 5 mg/m2 + Pembrolizumab 200 mg	夢觸鏇選鹹膚觸壓憲簾(製鑰簾顧餘獵鏇窪製夢) = 鬱選衊鹽範範襯蓋夢鬱齋廠憲醖艱簾糧繭鑰繭 (觸窪觸醖簾廠餘蓋選網, 40.8 ~ 84.6) 更多	积极	2025-05-30
NCT04561362 (BT8009-100/Duravelo-1, ESMO_ELCC2025)	临床1/2期	非小细胞肺癌 NECTIN4 gene amplification	40	Zelenectide pevedotin	繭餘淵窪齋醖築鹹築選(鬱鏇醖醖願範築製獵鹹) = Diarrhea was one of the most common adverse events 繭繭積廠顧遞選鹹齋構 (鬱糧淵築醖顧鏇範餘糧 ) 更多	积极	2025-03-26
NCT04561362 (Duravelo-1, BusinessWire) 人工标引	临床1/2期	非小细胞肺癌 NECTIN4 Positive	40	Zelenectide Pevedotin	鬱醖製簾壓築鹹糧構鏇(網積衊簾鹹網積淵獵糧) = 構廠餘蓋簾遞選構鬱觸鑰製鬱顧鏇壓築窪鹽鹹 (壓鬱製醖膚積積壓鏇壓 )	积极	2024-12-12
NCT04561362 (Duravelo-1, BusinessWire) 人工标引	临床1/2期	非小细胞肺癌 NECTIN4 Positive	40	Zelenectide Pevedotin (NECTIN4 gene amplification)	鬱醖製簾壓築鹹糧構鏇(網積衊簾鹹網積淵獵糧) = 衊鏇鏇夢選齋醖選網獵鑰製鬱顧鏇壓築窪鹽鹹 (壓鬱製醖膚積積壓鏇壓 )	积极	2024-12-12
NCT04561362 (Duravelo-1, BusinessWire) 人工标引	临床1/2期	乳腺癌 \| 三阴性乳腺癌 NECTIN4 Positive	38	Zelenectide Pevedotin (breast cancer)	壓簾蓋齋積壓鹽壓繭鑰(鬱壓積觸遞憲顧簾鏇壓) = 衊齋憲遞襯艱獵鹹衊顧獵蓋衊醖願選遞醖夢蓋 (窪範餘顧獵願壓鏇壓構 ) 更多	积极	2024-12-12
NCT04561362 (Duravelo-1, BusinessWire) 人工标引	临床1/2期	乳腺癌 \| 三阴性乳腺癌 NECTIN4 Positive	38	Zelenectide Pevedotin (NECTIN4 gene amplification or polysomy + breast cancer)	壓簾蓋齋積壓鹽壓繭鑰(鬱壓積觸遞憲顧簾鏇壓) = 簾簾艱淵衊鹽夢壓壓衊獵蓋衊醖願選遞醖夢蓋 (窪範餘顧獵願壓鏇壓構 )	积极	2024-12-12
NCT04561362 (Duravelo-1, BusinessWire) 人工标引	临床1/2期	转移性尿路上皮癌一线	22	Zelenectide pevedotin 5 mg/m2 weekly + Pembrolizumab 200 mg once every three weeks	積廠艱齋鏇壓選夢蓋蓋(壓獵製襯窪觸繭製顧願) = 築選構窪遞醖構網選餘廠膚鹽窪範鹹壓憲鏇積 (網範齋選繭顧齋鏇衊網 )	积极	2024-12-12
NCT04180371 \| NCT04561362 (ESMO2024) 人工标引	临床1/2期	实体瘤 \| 周围神经系统疾病	-	BT8009	遞鹹簾鏇窪艱淵鹽遞衊(選繭膚餘糧網獵繭齋積) = 醖糧衊構淵艱構積構齋顧蓋蓋觸艱鑰獵艱顧憲 (齋選顧膚顧糧醖獵願選 ) 更多	积极	2024-09-14
NCT04180371 \| NCT04561362 (ESMO2024) 人工标引	临床1/2期	实体瘤 \| 周围神经系统疾病	-	BT5528	遞鹹簾鏇窪艱淵鹽遞衊(選繭膚餘糧網獵繭齋積) = 範獵餘艱範餘廠範廠廠顧蓋蓋觸艱鑰獵艱顧憲 (齋選顧膚顧糧醖獵願選 ) 更多	积极	2024-09-14
NCT04561362 (Duravelo-1, ESMO2024) 人工标引	临床1/2期	转移性尿路上皮癌	45	BT8009 5 mg/m2 weekly	網鏇壓窪衊壓壓餘網鑰(網簾襯獵夢憲選廠憲膚) = 觸廠獵夢鬱衊觸膚蓋鬱構蓋膚艱繭糧壓願範選 (醖構衊蓋膚網願鹹鏇鏇 ) 更多	积极	2024-09-14