▎药明康德内容团队编辑
本期看点
1. 在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据，患者的疾病控制率（DCR）达91%，无进展生存期（PFS）数据令人鼓舞。
2. 放射治疗药物Rhenium（186Re）obisbemeda治疗胶质母细胞瘤（GBM）的1期临床试验结果亮眼，接受大于100 Gy该药治疗的患者的中位总生存期（OS）为17个月，是接受标准治疗患者的中位OS（8个月）的两倍多。
3. 首个利用碱基编辑疗法，在体内纠正致病基因突变的临床试验结果出炉，代表着体内碱基编辑疗法的临床概念验证。
药明康德内容团队整理
AVA6000：公布1a期临床试验数据
Avacta Therapeutics公司宣布，其在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据，该公司已开始招募1b期扩展队列，多名患者接受了治疗。唾液腺癌是一种在转移性阶段尚无标准治疗方案的疾病。AVA6000是Avacta研发管线中的首个多肽偶联药物，由阿霉素（doxorubicin）与Avacta专有的pre|CISION多肽偶联而成，该多肽可在肿瘤微环境中由成纤维细胞激活蛋白-α（FAP）特异性切割。FAP在大多数实体瘤中，与健康组织相比表达水平显著升高。Avacta的多肽偶联药物利用这一特征在肿瘤微环境中特异性释放活性药物，从而降低系统暴露和毒性，为患者提供最佳治疗效果。
此次公布的数据显示，与常规治疗患者相比，在接受AVA6000治疗的唾液腺癌患者中观察到令人鼓舞的PFS数据。在接受250 mg/m²及以上剂量治疗的11名唾液腺癌患者中，DCR达91%，5名患者肿瘤显著缩小，其中包括1例部分缓解（PR，肿瘤缩小超过30%）和4例轻微缓解（MR，肿瘤缩小10%-29%）。中位随访时间约为5个月，尚未达到中位PFS，而先前研究中使用常规抗癌治疗患者的中位PFS约为3.5个月。安全性方面，AVA6000的耐受性良好，没有观察到与常规剂量阿霉素相关的严重心脏毒性事件。
Rhenium（186Re）obisbemeda：公布1期临床试验的中期数据
Plus Therapeutics公司宣布，其主打放射治疗药物Rhenium（186Re）obisbemeda治疗胶质母细胞瘤的1期临床试验结果已发表在Nature Communications上。该疗法是一款新型可注射放疗药物，专门配制用于以安全、有效和方便的方式在中枢神经系统（CNS）肿瘤中递送专一靶向的高剂量辐射，以优化患者临床结局。由于186Re的半衰期短，具有破坏癌组织的β放射能和可用于活体成像的γ放射能，是CNS治疗应用的理想放射性同位素。
此次公布的结果显示，21名患者的中位OS为11个月，12名接受超过100 Gy辐射剂量的患者的中位OS为17个月，是接受标准治疗的复发性GBM患者的中位OS（约8个月）的两倍多。安全性方面，未观察到剂量限制性毒性，且大多数不良事件与研究治疗无关。
BEAM-302：公布1/2期临床试验数据
Beam Therapeutics公布了在研单碱基编辑疗法BEAM-302用于治疗α1抗胰蛋白酶缺乏症（AATD）患者的。BEAM-302是一种针对肝脏的脂质纳米颗粒（LNP）配方，内含指导RNA（gRNA）和编码碱基编辑器的mRNA，旨在修正致病的PiZ突变。新闻稿指出，这是首个利用碱基编辑疗法，在体内纠正致病基因突变的临床试验结果，代表着体内碱基编辑疗法的临床概念验证。
此次公布的结果显示，在单次输注BEAM-302后，观察到血液循环中总α-1抗胰蛋白酶（AAT）迅速、持久且呈剂量依赖性增加，新产生的具有治疗水平的修正蛋白AAT，以及突变型AAT的减少。在接受治疗后第7天便观察到总AAT的变化，第21天左右达到平台期，并在随访期间持续存在。中性粒细胞弹性蛋白酶抑制及结合检测均证实，增加的AAT具有功能性。在迄今探索的所有剂量水平下，BEAM-302治疗均显示出良好的耐受性和可接受的安全性。
▲BEAM-302的临床试验数据（图片来源：参考资料[3]）
IMC-M113V：公布1/2期临床试验数据
Immunocore公司公布了其在研疗法IMC-M113V治疗HIV感染者的1/2期临床试验的初步数据。IMC-M113V利用一种T细胞受体与HIV感染免疫细胞上的HLA-A*02:01-Gag复合物结合。该分子的抗CD3效应臂随后招募T细胞摧毁含有整合HIV DNA的CD4阳性细胞，消灭所谓的病毒储存库。
数据显示，IMC-M113V耐受性良好，并在中断抗逆转录病毒治疗（ART）后呈现剂量依赖性控制病毒的迹象。在15名可评估的HIV感染者中，120微克队列中1人、300微克队列中2人在分析性ART治疗中断（ATI）期间观察到延迟病毒反弹的情况。这3名显示病毒控制的患者在第8周的病毒载量约为200 c/mL。此外，这3名患者中有2人在预先规定的12周ATI期间始终未接受ART治疗。该试验的多次递增剂量（MAD）部分仍在进行中，正在评估更高剂量，随后还将设立一个或多个剂量的扩展队列。
QRL-101：公布1期临床试验数据
QurAlis Corporation公司宣布，其QRL-101的1期机制验证（PoM）临床试验在健康受试者中取得了积极的顶线数据，该试验旨在评估与肌萎缩侧索硬化（ALS）和癫痫相关的生物标志物。QRL-101是一种潜在“best-in-class”的选择性Kv7.2/7.3离子通道开放剂，用于治疗ALS患者由于过度兴奋引起的疾病进展，这种现象在散发性和遗传性ALS中均有发生，多数由KCNQ2基因mRNA前体的错误剪接引起。Kv7通道也是经临床验证的调节癫痫过度兴奋状态的有效靶点。体内和体外研究表明，与选择性较差的第一代Kv7.2/7.3通道开放剂ezogabine相比，QRL-101显示出更高的效力，并可能引发更少的临床不良事件。
此次公布的结果显示，QRL-101在ALS相关的主要终点——运动神经兴奋性阈值追踪（mNETT）强度-时间常数（SDTC）上表现出剂量依赖性的显著降低，降幅比第一代Kv7.2/7.3通道开放剂在ALS患者中的单剂量研究结果高出约50%。此外，QRL-101对癫痫相关的多个次要和探索性终点也显示出显著影响，表明其能有效透过血脑屏障并具有潜在的抗癫痫作用。安全性方面，QRL-101的安全性和耐受性与其之前的研究结果一致，未报告严重不良事件或因不良事件导致的停药。
RXRG001：1/2a期临床试验完成首例患者给药
转录本生物科技有限公司（RiboX Therapeutics，简称RiboX）宣布，RXRG001用于治疗辐射诱导的口干症和唾液分泌不足的1/2a期临床试验已完成首例患者给药。RXRG001是RiboX自主研发的由LNP包裹的环形RNA药物，通过LNP递送环形RNA在唾液腺中表达水通道蛋白AQP1增强透水性，从而提高进入口腔中的唾液流量及流速，改善患者口干症状。临床前研究显示，RXRG001展现了持久疗效同时具备良好的耐受性和安全性。单次给药后可显著增加唾液流量，并且效果可持续长达四周。新闻稿指出，RXRG001是全球首个获FDA许可进入临床试验的环形RNA疗法。
TVB-3567：IND申请获得FDA许可
Sagimet Biosciences公司宣布，其用于治疗痤疮的脂肪酸合成酶（FASN）抑制剂TVB-3567的IND申请已获得批准。TVB-3567是一种强效的选择性小分子FASN抑制剂，计划于2025年开始首次人体1期临床试验。痤疮的发生与皮肤中皮脂分泌增加密切相关。FASN是从头脂肪生成途径中的最后一步，该途径产生约80%的皮脂脂质。先前的临床前和临床研究表明，FASN抑制剂可以改善皮脂成分并显著减少痤疮病变，有潜力作为治疗痤疮的靶点。
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参考资料（可上下滑动查看）
[1] Avacta Announces Promising Early Efficacy and Safety Data for AVA6000 in the Phase 1a Dose Escalation and Ongoing Enrollment in the Phase 1b Expansion Cohorts. Retrieved March 14, 2025, from https://www.globenewswire.com/news-release/2025/03/07/3039002/0/en/Avacta-Announces-Promising-Early-Efficacy-and-Safety-Data-for-AVA6000-in-the-Phase-1a-Dose-Escalation-and-Ongoing-Enrollment-in-the-Phase-1b-Expansion-Cohorts.html
[2] Plus Therapeutics Announces Peer-Reviewed Publication in Nature Communications Highlighting Promising Phase 1 Results for Rhenium (186Re) Obisbemeda in Glioblastoma. Retrieved March 14, 2025, from https://www.globenewswire.com/news-release/2025/03/07/3038883/0/en/Plus-Therapeutics-Announces-Peer-Reviewed-Publication-in-Nature-Communications-Highlighting-Promising-Phase-1-Results-for-Rhenium-186Re-Obisbemeda-in-Glioblastoma.html
[3] Beam Therapeutics Announces Positive Initial Data for BEAM-302 in the Phase 1/2 Trial in Alpha-1 Antitrypsin Deficiency (AATD), Demonstrating First Ever Clinical Genetic Correction of a Disease-causing Mutation. Retrieved March 10, 2025, from https://www.globenewswire.com/news-release/2025/03/10/3039523/0/en/Beam-Therapeutics-Announces-Positive-Initial-Data-for-BEAM-302-in-the-Phase-1-2-Trial-in-Alpha-1-Antitrypsin-Deficiency-AATD-Demonstrating-First-Ever-Clinical-Genetic-Correction-of.html
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免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。
