高达12.35亿美元PDC合作！PeptiDream 和礼来就多肽偶联药物达成一项新的合作协议

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关键词：礼来协议药物合作合作协议药

资讯来源：药时代

发布时间： 2022-12-28

药时代创新药BD高阶研讨会火热报名中！

</section></section></section></section></section></section><section arial="" center="" gb="" helvetica="" neue="" normal="" rgb="" sans="" sans-serif="" sc="" style="margin-bottom: 0px;padding-right: 10px;padding-left: 10px;outline: 0px;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" visible="" yahei=""><span style="outline: 0px;letter-spacing: 0.544px;visibility: visible;color: rgb(232, 22, 105);"><strong style="outline: 0px;visibility: visible;"><span style="outline: 0px;letter-spacing: 0.544px;font-size: 15px;visibility: visible;">请点击左下方【阅读原文】报名！</span></strong></span></section><section arial="" center="" gb="" helvetica="" neue="" normal="" rgb="" sans="" sans-serif="" sc="" style="margin-bottom: 0px;padding-right: 10px;padding-left: 10px;outline: 0px;color: rgb(34, 34, 34);font-family: system-ui, -apple-system, BlinkMacSystemFont, " ui="" visible="" yahei=""><span style="outline: 0px;letter-spacing: 0.544px;visibility: visible;color: rgb(232, 22, 105);"><strong style="outline: 0px;visibility: visible;"><span style="outline: 0px;letter-spacing: 0.544px;font-size: 15px;visibility: visible;"><br/></span></strong></span></section><section style="margin-top: 5px;margin-bottom: 20px;text-align: justify;line-height: 1.75em;"><span style="font-size: 16px;background-color: rgb(255, 255, 255);text-align: justify;">2022 年 12 月 26 日，PeptiDream宣布已与礼来建立合作伙伴关系，共同开发新型多肽偶联药物(PDC)。</span><span style="font-size: 16px;background-color: rgb(255, 255, 255);text-align: justify;">双方将利用专有的药物发现和开发平台 PDPS（肽发现平台系统）向目标细胞和组织递送有效载荷，从而识别具有结合特性的独特环肽。</span><span style="font-size: 16px;background-color: rgb(255, 255, 255);text-align: justify;">PeptiDream负责创建和优化肽，礼来负责创建和优化有效载荷，并承担基于这项合作研究PDC 产品的开发费用。</span><br/></section><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: justify;"><span style="font-size: 16px;">根据协议条款，PeptiDream将收到礼来的预付款，并有望获得总额高达 12.35 亿美元（约合 1630 亿日元）的开发、审批和营销里程碑费用，并根据商业化后的销售额收取特许权使用费。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img js_insertlocalimg" data-ratio="0.3106796116504854" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/b76a6a70e0d712b7808fbf269f1f72ac.png" data-type="png" data-w="515" style="width: 491px;height: 153px;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 18px;color: rgb(16, 101, 230);"><strong>关于PeptiDream</strong></span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">PeptiDream旨在通过生产特殊环肽的新型创新药物，来满足未满足的医疗需求并改善全世界人民的生活质量。自2006年成立以来，公司基于一个独特的药物发现和开发平台，已生成数万亿肽库，并从库中高效地筛选出有前景、高选择性的非标准环肽。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">利用PDPS（Peptide Discovery Platform System）技术，公司促进肽药物发现、小分子药物发现以及使用肽-药物偶联物 (PDC) 的治疗和诊断药物的发展。目前，已与多家跨国药企合作，包括礼来、默沙东、罗氏、诺华、强生、盐野义等。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img js_insertlocalimg" data-backh="278" data-backw="468" data-croporisrc="https://mmbiz.qpic.cn/mmbiz_png/V5wksYicgp8ibLy48zVQShWzLdZc0icdhI5PuYxA1RFx5yaa405P1PAn4QntD1hiaPOrdM5TswpFBpPOtPndXibnnGw/0?wx_fmt=png" data-cropx1="0" data-cropx2="864.9999999999999" data-cropy1="82.30968858131487" data-cropy2="595.6228373702422" data-ratio="0.5942196531791908" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/9b92c4b1ea9904fcf1f5c89a6b85df16.jpeg" data-type="jpeg" data-w="865" style="width: 100%;height: auto;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">PDC作为该公司的布局重点，目前已有多个项目在研。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img js_insertlocalimg" data-backh="260" data-backw="543" data-croporisrc="https://mmbiz.qpic.cn/mmbiz_png/V5wksYicgp8ibLy48zVQShWzLdZc0icdhI56gxuJpvlNJUNlPfjAiaTiaHXRYryA25WiaAaRxShr5iaHdmwwsvEdNVaeQ/0?wx_fmt=png" data-cropx1="0" data-cropx2="865" data-cropy1="68.84083044982698" data-cropy2="481.8858131487889" data-ratio="0.47861271676300576" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/efff1d456b081bd79a7209bb3e7c1fc4.jpeg" data-type="jpeg" data-w="865" style="width: 100%;height: auto;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">其中，布局PDC涉及靶点包括PD-L1、CD38、TfR、c-Met等。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img js_insertlocalimg" data-backh="237" data-backw="492" data-croporisrc="https://mmbiz.qpic.cn/mmbiz_png/V5wksYicgp8ibLy48zVQShWzLdZc0icdhI5YOYvy99g6IvbXvVvZdCd5CXR7GRZ7haqpnKHVDrLbDubHEa5ibxZzoQ/0?wx_fmt=png" data-cropx1="0" data-cropx2="865" data-cropy1="68.84083044982698" data-cropy2="483.38235294117646" data-ratio="0.48092485549132946" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/6768ee75b8cc355beac10fdb49cc1f36.jpeg" data-type="jpeg" data-w="865" style="width: 100%;height: auto;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">目前，公司建立一个广泛的全球联合研发合作伙伴网络，还通过其全资子公司 PDR Pharma 在日本销售放射性药物。</span></p><p style="text-align: center;margin-bottom: 24px;"><img class="rich_pages wxw-img" data-backh="253" data-backw="525" data-galleryid="" data-ratio="0.48184818481848185" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/8e59d6b8a796c416cfd3b93e352f7743.png" data-type="png" data-w="1212" style="width: 100%;height: auto;"/><span style="font-size: 16px;background-color: rgb(255, 255, 255);text-align: justify;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 18px;color: rgb(16, 101, 230);"><strong>关于PDC</strong></span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">PDC结构主要包含：靶向多肽、连接子（Linker）和细胞毒素。可分解的Linker将特定的多肽序列与细胞毒素共价结合，三者协同作用，通过靶向肿瘤细胞的特定受体传递细胞毒素。PDC结构与ADC相似，只是归巢装置有所不同（将抗体换成靶向多肽）。它将细胞毒素以提高局部浓度的形式靶向递送至患病组织，减轻非疾病组织中的毒性效应，从而减轻不良反应，达到增效减毒的目的。与ADC相比，PDC具有分子量小、肿瘤穿透性强、免疫原性低、利用固相合成法可大规模合成、生产成本较低、相对较好的药代动力学等特点。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img" data-backh="202" data-backw="491" data-ratio="0.4123616236162362" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/9faee228c318d2a608ab81e2418773e2.jpeg" data-type="jpeg" data-w="1084" style="outline: 0px;display: initial;box-sizing: border-box !important;overflow-wrap: break-word !important;width: 100%;visibility: visible !important;height: auto;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">然而，由于多肽分子量相对较小，与多肽相似，PDC的缺陷之一是其循环稳定性差，会很快被肾脏清除。而且，PDC必须在循环内保持稳定，以防止细胞毒性有效载荷提前释放并导致全身暴露。此外，与单抗相比，多肽的组织特异性以及肿瘤靶向性稍有逊色，给靶向肽的筛选增加一些难度。可见，研发出具有靶向功能的穿膜肽技术、提高靶向肽的细胞穿透能力和稳定性是PDC 目前亟需解决的问题。另外，由于PDC的口服生物利用度极其有限，需要通过注射给药，研究者们正在尝试改进这一现象，包括通过不同修饰增强其化学和酶稳定性，使用以受控方式递送多肽和蛋白质的新纳米材料。</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img" data-backh="288" data-backw="502" data-ratio="0.5728395061728395" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/f87aaa3d4bb1a78c6e26c198f66b6be2.jpeg" data-type="gif" data-w="810" style="outline: 0px;display: initial;width: 100%;height: auto;box-sizing: border-box !important;overflow-wrap: break-word !important;visibility: visible !important;"/></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">目前只有两种PDC被FDA批准用于癌症治疗：Melflufen和177Lu-dotatate。Melfulfen是目前已获批的一种高度亲脂性的PDC，它利用增加的氨基肽酶活性选择性地增加肿瘤细胞内细胞毒性烷化剂的释放和浓度，目前应用于多发性骨髓瘤的治疗；177Lu dotatate是一种结合生长抑素类似物和放射性核素的靶向放射治疗形式，它被批准用于治疗胃肠胰神经内分泌肿瘤。将处于在研阶段PDC统计如下：</span></p><p style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;text-align: center;"><img class="rich_pages wxw-img" data-backh="725" data-backw="449" data-galleryid="" data-ratio="1.6146993318485523" data-s="300,640" src="https://zfz-oss.oss-cn-hangzhou.aliyuncs.com/temp/385c77db4cd4cb0058e6ad35baec451a.png" data-type="png" data-w="449" style="outline: 0px;display: initial;box-sizing: border-box !important;overflow-wrap: break-word !important;visibility: visible !important;width: 100%;height: auto;"/></p><section style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;">在研究企业上，除了Cybrexa 、Bicycle Therapeutics、Oncopeptipes等代表企业外，包括诺华、阿斯利康、罗氏等在内的大型医药公司，以及盛诺基、盟科、博瑞医药、泰尔康生物等多家中国公司，也在PDC领域进行布局与开发。根据头豹研究院预测，2026年全球已上市ADC药物市场规模预计将超过164亿美元。PDC作为一种新颖的治疗方式，有望克服ADC的某些局限性。我们期望出现更安全、更有效的肿瘤靶向PDC，为难治性癌症患者带来希望。</span></section><section style="margin-top: 15px;margin-bottom: 10px;white-space: normal;background-color: rgb(255, 255, 255);box-sizing: border-box;line-height: 1.75em;"><span style="font-size: 16px;"><br/></span></section><p arial="" gb="" helvetica="" neue="" rgb="" right="" sans="" sans-serif="" sc="" style="margin-right: 8px;margin-bottom: 0px;margin-left: 8px;white-space: normal;outline: 0px;color: rgb(34, 34, 34);font-family: 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