HX-009

SAN DIEGO--(BUSINESS WIRE)-- Crown Biosciences Inc., a global contract research organization (CRO) and JSR Life Sciences company, has announced that its collaborative work with HanX Biopharmaceuticals, Inc. (“HanX”), employing a unique and broad portfolio of preclinical modeling in support of HanX’s successful FDA Investigational New Drug (IND) application, has been published in Scientific Reports, a journal within the Nature portfolio. The study demonstrated that HX009, an investigational “first-in-class” PD-1 x CD47 bispecific antibody, binds differentially to both PD-1 and CD47 with strong affinity to PD-1 but weakened affinity to CD47. This feature enables better targeting to the tumor microenvironment (TME) and minimizes potential hematological toxicity. In addition, HX009 exhibited enhanced T-cell activating capability over HX008, an approved and marketed anti-PD-1 monoclonal antibody in China. Specifically, this new study showed that HX009 exerted robust anti-lymphoma activity in two cell-derived xenograft (CDX) models (Raji B-lymphoma and Karpas-299 T-lymphoma) with high CD47 expression. Additionally, custom patient-derived xenograft (PDX) models established by Crown Bioscience, further confirmed the efficacy of CD47 targeting by HX009. In addition, an A20-hCD47 mouse B-lymphoma model developed in hSIRPα/hCD47/PD-1/PD-L1 quadruple knock-in genetically engineered mouse models (HuGEMMTM) mice, HX009 exhibited superior anti-lymphoma efficacy compared to CD47 or PD-1 targeting alone. These results imply a synergy between CD47 and PD-1 dual targeting. These Crown Bioscience studies played an important role in supporting the application of HX009 for the treatment of lymphoma in clinical trials. They also played an instrumental role in supporting the clearance of HanX’s FDA Investigational New Drug (IND) application, which has paved the way for a U.S.-based Phase I/II clinical study that will assess HX009 in the treatment of relapsed/refractory lymphoma. This exciting result exemplifies the value that Crown Bioscience brings to its partners as they seek better solutions for advancing their oncology research. Specifically, the collaboration between scientists from both organizations, utilizing an integrated solution approach, leveraged a comprehensive collection of preclinical and translational studies to investigate the anti-lymphoma activity of HX009. While HX009 has been studied in Phase I clinical studies in Australia and China in both solid tumor and lymphoma indications, HanX is now expanding the next phase of clinical development globally in a variety of clinical indications. Henry Li, PhD, Cofounder, Chief Executive Officer and Chief Scientific Officer of HanX, stated: “We are delighted with the exceptional outcomes of our partnership with Crown Bioscience. By leveraging a wide breadth of in vivo solutions such as cell-derived xenograft (CDX), patient-derived xenograft (PDX), and genetically engineered mouse models, together with translational applications, we were able to conduct a comprehensive evaluation of HX009’s anti-lymphoma activity prior to clinical trials.” Ludovic Bourre, PhD, VP, Research and Innovation at Crown Bioscience, added: “Our commitment goes beyond identifying the right candidate drug or drug combination. Crown Bioscience consistently invests in expanding the number and diversity of models for drug development, ensuring that our models accurately represent the relevant clinical disease biology and provide a solid foundation for making informed decisions about novel therapeutics such as HanX's HX009.” This work has laid a robust foundation for the advancement of HX009 as a highly promising therapeutic agent in the treatment of relapsed/refractory lymphoma. To learn more, Crown Bioscience and HanX are hosting an exclusive webinar on Tuesday August 29, 2023, where a team of scientists will discuss the implications of the study. The webinar will provide a unique opportunity to engage with the experts. ### About Crown Bioscience Crown Bioscience, a JSR Life Sciences company, is a global CRO that provides preclinical and translational platforms to help our customers advance their research and development in oncology, immuno-oncology, and immune-mediated inflammatory diseases. We are the exclusive preclinical CRO to offer tumor organoid services with the well-established Hubrecht Organoid Technology. In addition, we have developed the largest commercially available PDX collection in the world. We focus on helping our customers develop novel therapies to maximize the chances that patients receive the right treatment at the right time. Founded in 2006, Crown Bioscience has 14 facilities across the United States, Europe, and Asia. For more information or to get in touch, please visit About HanX HanX is a global biopharmaceutical company that develops innovative immuno-oncology antibody-based drugs, such as novel BsAb antibodies to address significant unmet medical needs. HanX brings together experts from both China and the U.S., to aid in activities ranging from early discovery, process development, business development, and clinical research. The company aims to accomplish its ambitious goals by relying on in-house research and development in combination with external global collaborations.

点击蓝字关注我们本周，审评审批方面，两大明星国产PD-1单抗都有新进展。君实PD-1特瑞普利单抗乳腺癌适应症申报上市，当前国产PD-1/L1抑制剂并未有获批乳腺癌适应症，特瑞普利单抗为国产首款。百济神州PD-1替雷利珠单抗第11个适应症获批上市，一线治疗食管鳞癌，集齐五大一线适应症。研发方面，进口PD-L1也有新突破，阿斯利康PD-L1度伐利尤单抗一线子宫内膜癌Ⅲ期成功。本期盘点包括审评审批和研发两大板块，统计时间为5.22-5.26，包含23条信息。 审评审批NMPA上市批准       1、5月23日，NMPA官网显示，拜耳的注射用盐酸可泮利塞（copanlisib）获批上市，用于治疗既往至少接受过两种系统性治疗的复发或难治性滤泡性淋巴瘤（FL）成人患者。注射用盐酸可泮利塞正是一款静脉注射的PI3K抑制剂，它能够在亚纳摩尔水平上抑制主要表达在恶性B细胞中的PI3K-α和PI3K-δ两种激酶亚型。2、5月23日，NMPA官网显示，百济神州的替雷利珠单抗（商品名：百泽安）第11项适应症获批上市，联合化疗用于一线治疗不可切除的局部晚期、复发或转移性食管鳞状细胞癌（ESCC）。替雷利珠单抗是一款人源化IgG4抗程序性死亡受体-1（PD-1）单抗。3、5月23日，NMPA官网显示，迈博药业的注射用CMAB007获批上市，用于治疗过敏性哮喘。CMAB007是一款奥马珠单抗生物类似药，奥马珠单抗原研药由诺华和罗氏合作开发，是一款专门针对和阻断抗免疫球蛋白E（IgE）的抗体治疗药物。4、5月23日，NMPA官网显示，强生旗下杨森的CD38单抗达雷妥尤单抗注射液（皮下注射）第2项适应症获批上市。达雷妥尤单抗皮下注射剂型可以在大约3到5分钟内给药，与该产品静脉注射剂相比，能够将患者的给药时间从几小时缩短到几分钟。此前，该产品已在中国获批用于治疗原发性轻链型淀粉样变患者。申请5、5月22日，CDE官网显示，正大天晴的罗沙司他胶囊递交上市申请并获受理。这是国内首款申报上市的罗沙司他仿制药。原研产品由FibroGen/阿斯利康联合开发，已在中国获批上市，商品名爱瑞卓，用于治疗透析（DD）和非透析（NDD）慢性肾病成人患者贫血。6、5月22日，CDE官网显示，君实生物的PD-1单抗药物特瑞普利单抗第8项适应递交上市申请并获受理，联合注射用紫杉醇（白蛋白结合型）用于PD-L1阳性（CPS≥1）的初治转移或复发转移性三阴性乳腺癌的治疗。7、5月22日，CDE官网显示，罗氏5.1类新药恩曲替尼胶囊的新适应症递交上市申请并获受理，用于携NTRK融合基因阳性实体瘤、ROS1阳性的局部晚期或转移性非小细胞肺癌（NSCLC）等适应症。恩曲替尼是一款靶向泛TRK及ROS1酪氨酸激酶的具有中枢神经系统（CNS）活性的强效选择性抑制剂，能够穿过血脑屏障。8、5月24日，CDE官网显示，正大天晴3.3类新药帕妥珠单抗递交上市申请并获受理。帕妥珠单抗是一种靶向HER2受体的单克隆抗体药物，被设计用于阻止HER2受体与其他EGFR家族成员配对形成二聚体，从而阻碍下游细胞信号的激活，遏制肿瘤的生长。原研产品已在中国获批治疗乳腺癌。9、5月25日，CDE官网显示，勃林格殷格翰的佩索利单抗注射液（皮下注射）递交上市申请并获受理。佩索利单抗是一款选择性靶向白细胞介素-36受体（IL-36R）抗体，其静脉注射液已在中国获批用于治疗成人泛发性脓疱型银屑病（GPP）发作。临床批准       10、5月22日，CDE官网显示，恒瑞医药1类新药注射用SHR-2001获批临床，拟用于治疗系统性红斑狼疮（SLE）。注射用SHR-2001是一种抗体-细胞因子融合蛋白，剂型为冻干粉针剂，临床皮下注射给药。SLE发病机制复杂，包括自身反应性T细胞与B细胞的增殖活化、多种自身致病性抗体的产生、细胞因子分泌及其受体表达异常等。11、5月22日，CDE官网显示，恒瑞医药1类新药SHR-1654注射液获批临床，拟用于治疗类风湿关节炎。SHR-1654注射液是临床皮下注射给药。类风湿关节炎是一种慢性、炎症性自身免疫系统疾病，可引发一系列症状，包括关节部位的疼痛和肿胀，尤其是手、足和膝关节部位。12、5月22日，CDE官网显示，辉瑞的zavegepant鼻喷雾剂获批临床，拟用于治疗成人偏头痛的急性期治疗（有或无先兆）。Zavegepant是BiohavenPharmaceutical研发的一款第三代高亲和力、高选择性的小分子CGRP受体拮抗剂，已在美国获批用于急性治疗偏头痛成人患者，可在15分钟内快速起效。申请       13、5月22日，CDE网站显示，安斯泰来的ASP3082注射液申报临床。ASP3082是安斯泰来开发的一款高效选择性KRASG12D蛋白降解剂（PROTAC）。临床前数据显示，ASP3082能够有效降解KRASG12D蛋白，对细胞外信号调节激酶磷酸化及其下游基因具有显著的抑制作用，并有效诱导半胱天冬酶-3的切割。优先审评14、5月25日，CDE官网显示，正大天晴1类新药TQ-B3525片的上市申请拟纳入优先审评，拟用于既往接受过至少两种系统性治疗的复发或难治性滤泡性淋巴瘤患者。这是一款新型PI3Kα/δ双重抑制剂，可克服单独抑制PI3Kδ亚基时引起的PI3Kα亚基活性上调而引发的耐药问题。突破性治疗15、5月26日，CDE官网显示，由亚盛医药全资子公司顺健生物的耐克替尼片拟纳入突破性治疗品种，拟开发适应症为：既往经过一线治疗的琥珀酸脱氢酶（SDH）缺陷型胃肠道间质瘤（GIST）。该药属于第三代BCR-ABLTKI奥雷巴替尼（HQP1351），此前已在中国获批用于治疗慢性髓细胞白血病（CML）慢性期或加速期的成年患者。FDA上市      申请       16、5月26日，FDA官网显示，和黄医药与武田的呋喹替尼递交上市申请并获受理，拟用于治疗经治转移性结直肠癌成人患者，并授予其优先审评资格，PDUFA日期为2023年11月30日。呋喹替尼是一种高选择性、强效的口服VEGFR-1、-2及-3抑制剂。临床批准17、5月22日，FDA官网显示，翰思艾泰的HX009获批临床。这是一项即将在美国开展的Ⅰb/Ⅱ期临床研究，旨在评估HX009在经标准治疗失败后复发/难治淋巴瘤患者中的疗效。HX009是翰思艾泰研发的双特异性PD-1xCD47抗体，已在澳大利亚和中国开展了早期临床Ⅰ期试验。18、5月25日，FDA官网显示，英矽智能的ISM3091获批临床，将在实体瘤患者中开展Ⅰ期临床试验。ISM3091是一款口服高选择性小分子抑制剂，靶向调控DNA损伤和修复的新颖“合成致死”靶点—USP1。研发临床数据19、5月23日，GSK在美国胸科学会（ATS）年会以海报形式公布了其抗IL-5单抗美泊利珠单抗（商品名：新可来）中国Ⅲ期随机对照试验积极结果。该试验评价了该产品在中国重度嗜酸粒细胞性哮喘（SEA）患者中的有效性和安全性。结果表明，美泊利珠单抗可显著降低哮喘急性发作率，改善患者生活质量评分，并提高肺功能。20、5月25日，盛世泰科公布了DPP-4抑制剂盛格列汀两项Ⅲ期临床试验的数据及结果，50mg低剂量单药及联合用药的临床试验数据显示，对于不同糖尿病病史年限的患者都具有明显改善糖化血红蛋白的作用，同时，药物还显著改善β细胞功能，并降低收缩压。21、5月26日，迪哲医药在美国临床肿瘤学会（ASCO）年会官网公布了舒沃替尼的一项关键研究（悟空6，WU-KONG6）的口头报告摘要，该研究针对的适应症为治疗EGFR20号外显子插入（EGFRexon20ins）突变型晚期非小细胞肺癌（NSCLC）。试验数据显示，患者的客观缓解率（ORR）达到60.8%。22、5月26日，阿斯利康公布了Ⅲ期DUO-E研究的高水平阳性结果。在新诊断的晚期或复发子宫内膜癌患者中，与标准治疗化疗相比，度伐利尤单抗（Imfinzi）联合含铂化疗，之后使用奥拉帕利（Imfinzi+Lynparza）或单药Imfinzi作为维持治疗，在无进展生存期（PFS）方面具有统计学意义和临床意义的改善。Imfinzi联合Lynparza作为维持治疗有更大的临床获益。23、5月26日，百济神州公布了PD-1单抗雷利珠单抗Ⅲ期RATIONALE312研究数据，结果显示，相较于化疗，替雷利珠单抗（商品名：百泽安）联合化疗在未经治疗的广泛期小细胞肺癌（ES-SCLC）患者中展现出OS优效性。【企业推荐】智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~