Ladiratuzumab vedotin

//   美国新泽西州普林斯顿和中国苏州，2026年4月23日， —— 创胜医药(06628.HK)，一家具备生物药品发现、研发、工艺开发和生产全流程整合能力的临床阶段的国际生物制药公司，今日宣布在2026年美国癌症研究协会（AACR）年会上公布其靶向LIV1的专有抗体偶联药物（ADC）临床前研究数据。数据表明该药物具有显著的抗肿瘤活性、基于载荷差异化的疗效，以及良好的耐受性特征，支持其在LIV1阳性实体瘤中的进一步开发。 LIV1属于锌转运蛋白家族成员，在正常组织中表达有限，但在多种肿瘤中高频过表达，包括乳腺癌（93%）、前列腺癌（72%）及肺癌（10%），因此成为ADC药物开发中极具吸引力的细胞表面靶点。 创胜医药开发了48D6，一种新型专有人源化抗LIV1单克隆抗体，具有高亲和力、高特异性及良好的内吞能力。通过Retrogenix细胞微阵列技术评估，48D6被证实与其他人类蛋白无非特异性相互作用，确认了其高度的靶点特异性。基于48D6，创胜医药采用糖基转移酶介导的特定位点偶联平台开发了两款ADC候选药物：ADC-2（偶联拓扑异构酶I抑制剂载荷）和ADC-3（偶联MMAE载荷）。 在Balb/c小鼠中开展的药代动力学研究显示，ADC-2的半衰期约为10.4–11.6天，显著长于基准对照SGN-LIV1A类似物（3.7–3.9天），并与裸抗48D6（13.8–15.6天）相当，表明其具有良好的体内稳定性。 体内药效研究表明，在LIV1表达的ER阳性/HER2阴性乳腺癌及非小细胞肺癌（NSCLC）患者来源异种移植（PDX）模型中，ADC-2在每周一次、连续四周、剂量为6 mg/kg的给药方案下展现出显著的抗肿瘤活性。 在LIV1表达的前列腺癌PDX模型中，ADC-2在前两次给药后显示有限的肿瘤抑制作用。在第3次给药起替换为基于MMAE的ADC-3后，ADC-3对前列腺肿瘤生长产生了显著抑制作用。在LIV1高表达的前列腺癌PDX模型中，停止给药后，ADC-3对肿瘤生长的抑制作用持续超过70天。 在评估安全性与耐受性的探索性毒理学研究中，ADC-2在小鼠内经多次给药后，在所有测试剂量下均表现出良好耐受性。60 mg/kg组在给药期间观察到轻微损伤，但在恢复期结束时完全恢复。基于上述结果，ADC-2在小鼠中的最大耐受剂量（MTD）确定为60 mg/kg。ADC-3的安全性与耐受性尚未开展相关研究。 上述数据表明，创胜医药靶向LIV1的ADC-2及ADC-3在ER阳性/HER2阴性乳腺癌（占乳腺癌的60%）及前列腺癌PDX模型中作为单药治疗均展现出显著的抗肿瘤活性，且两者在小鼠中均表现出良好的耐受性。创胜开发的靶向LIV1的ADC在三阴性乳腺癌（TNBC）肿瘤模型中同样展现出显著的抗肿瘤活性，相关数据已于2024 SABCS公布。这些结果支持创胜医药进一步推进该产品在LIV1阳性实体瘤中的研究与开发。 创胜医药是一家临床阶段的在生物药发现、研发、工艺开发和生产方面具有全面综合能力的生物制药公司。 创胜医药总部位于苏州，已成功搭建了全球的业务布局：在苏州设有药物发现、临床和转化研究中心，在杭州拥有工艺与产品开发中心以及药物生产基地，在中国，美国和欧洲分别设有临床开发中心。创胜医药正在开发多元化的产品管线，包含数十种新型生物药，涵盖了肿瘤及非肿瘤适应症，包括骨科，自身免疫性疾病和肾脏疾病等。 如需了解关于创胜医药的更多信息，请访问公司网站：www.transcenta.com 或领英账号：Transcenta Therapeutics。如您有意了解我司资本合作事宜，敬请通过ir@transcenta.com 与我们建立联系，共探合作机遇。

PRINCETON, N.J. and SUZHOU, China, April 23, 2026 (GLOBE NEWSWIRE) -- Transcenta Therapeutics (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, today announced the presentation of preclinical data highlighting its proprietary LIV1-targeting antibody-drug conjugates (ADC) at the 2026 AACR Annual Meeting. The data demonstrate strong anti-tumor activity, differentiated payload-dependent efficacy, and favorable tolerability pro supporting further development in LIV1-positive solid tumors. LIV1 is a member of the zinc transporter family, with limited normal tissue expression, and is found to be overexpressed with high prevalence in breast (93%), prostate (72%) and lung (10%) cancers, making it an attractive cell surface target for developing ADC therapeutics. Transcenta Therapeutics has developed 48D6, a novel proprietary humanized anti-LIV1 monoclonal antibody with high affinity, specificity, and internalization capability. Using Retrogenix cell microarray technology, 48D6 demonstrated no non-specific interactions with other human proteins, confirming its high target specificity. Leveraging 48D6, Transcenta Therapeutics then generated two ADC candidates using a glycotransferase-mediated site-specific conjugation platform: ADC-2, conjugated with a Topoisomerase I inhibitor payload, and ADC-3, conjugated with MMAE. Pharmacokinetic studies in Balb/c mice showed that ADC-2 exhibited a half-life of approximately 10.4–11.6 days, significantly longer than that of a benchmark SGN-LIV1A analog (3.7–3.9 days), and comparable to the naked antibody 48D6 (13.8–15.6 days), indicating favorable in vivo stability. In vivo efficacy studies demonstrated that ADC-2 elicited potent anti-tumor activity in LIV1-expressing ER+/HER2- breast cancer and non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models at a dose of 6 mg/kg administered once weekly for four weeks. For LIV1 expressing prostate PDX models, ADC-2 demonstrated limited tumor growth inhibition after two doses. After MMAE-based ADC-3 replaced ADC-2 from the 3rd dose, ADC-3 inhibited the growth of the prostate tumor significantly. In a LIV1 high expressing prostate PDX, the tumor growth was suppressed by ADC-3 for more than 70 days after the dosing was stopped. In exploratory toxicity studies to assess safety and tolerability, ADC-2 was well tolerated following repeated administrations in mice at all doses tested. Slight lesions were observed in 60 mg/kg group during the treatment period and fully recovered at the end of the recovery period. Based on these results, the maximum tolerated dose (MTD) of ADC-2 in mice was determined at 60 mg/kg. The safety and tolerability of ADC-3 has not yet been explored. Collectively, these data demonstrate that Transcenta’s LIV1-targeting ADC-2 and ADC-3 programs exhibited strong anti-tumor activities as monotherapy in PDX models of ER+/HER2- breast cancer (representing ~60% of all breast cancers) and also prostate cancer. ADC-2 also displayed excellent tolerability pro mice. Notably, Transcenta’s LIV1-targeting ADCs also demonstrated potent anti-tumor activity in triple-negative breast cancer (TNBC) tumor models, with data previously presented at the 2024 SABCS. These results support further investigation of Transcenta’s LIV1 ADCs in LIV1-positive solid tumors. About Transcenta Therapeutics Transcenta Therapeutics (HKEX: 06628) is a global clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta Therapeutics has established a global footprint, with its Headquarters and Discovery, Clinical and Translational Research Capabilities located in Suzhou, China, its Process and Product Development Center and Manufacturing Facility located in Hangzhou, China, and additional Clinical and Business Development Centers across China, the U.S. and Europe. Transcenta Therapeutics is developing a diverse pipeline of more than a dozen novel biologic therapies for oncology and selected non-oncology indications such as bone and kidney disorders. Media Contact: pr@transcenta.com