Recombinant Human Coagulation Factor VIII (Takeda)

Angus Smith joins as Chief Financial Officer Wing-Yen Wong, M.D., joins as interim Chief Medical Officer CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Be Biopharma, Inc. (“Be Bio”), a company pioneering the development of engineered B Cell Medicines (BCMs), today announced the appointment of Angus Smith as Chief Financial Officer (CFO) and Wing-Yen Wong, M.D., as interim Chief Medical Officer (CMO). Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, having held C-level positions in several public companies, including his most recent role as the CFO of Affimed N.V. and co-President of the company’s U.S. subsidiary, where he was responsible for implementing a new business plan and for raising over $400M in capital to support clinical development efforts. Mr. Smith also brings nearly a decade of investment banking experience, providing strategic and financial advice across the healthcare sector. Dr. Wong brings over 35 years of experience as a practicing clinician and professor at Children’s Hospital of Los Angeles, and leading development efforts in several companies including BioMarin, Biogen, and Baxter. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin where she was involved in the development of the most recently approved hemophilia gene therapy. “We are thrilled to welcome Angus and Wing to Be Bio,” said Joanne Smith-Farrell, Ph.D., Chief Executive Officer. “We are rapidly transitioning from a research-based company to one focused on delivering innovative medicines to patients, with our first program in hemophilia B entering the clinic this year. These accomplished and experienced leaders will further strengthen our leadership team. Angus’s long track record of financial operating experience and fundraising will be important as we advance multiple programs to the clinic, while Wing’s expertise in drug development and as a clinical scientist is particularly important as we pioneer a new class of cellular medicines, Engineered B Cell Medicines (BCMs), to dramatically improve the lives of patients.” Angus Smith Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, including his most recent role as the CFO of Affimed N.V. and, prior to that, at Rockwell Medical. At Affimed, Mr. Smith led all finance, accounting, and investor relations functions, implemented a new business plan and financing strategy, and raised more than $400 million. Mr. Smith began his career in healthcare investment banking, serving most recently as a Director in the Healthcare Investment Banking Group at Cantor Fitzgerald. During his nearly decade-long investment banking tenure, Mr. Smith provided strategic and financial advice to life sciences and healthcare companies. He has worked on a substantial number of transactions across the healthcare sector with an aggregate transaction value of more than $15 billion. Mr. Smith holds a B.A. in Mathematical Economics from Colgate University. Wing-Yen Wong, M.D. Dr. Wong brings over 35 years of experience as a practicing clinician and working in the biotechnology industry with a focus in the treatment and management of patients with hemophilia, sickle cell disease (SCD) and pediatric hematology/oncology. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin and Vice President, Global Medical, Hematology and Immunology at Biogen. Prior to Biogen, Dr. Wong was the Head of Clinical Research and Global Senior Medical Director of Hemophilia/Hematology at Baxter Healthcare Corporation where she directed medical and clinical functions, including global medical support of licensed products, clinical development and new product approvals. During her tenure at Baxter, Dr. Wong successfully directed the BLA submission and launch of multiple hemophilia products including RIXUBIS®, FEIBA®, OBIZUR and ADVATE®. Prior to her work in industry, Dr. Wong spent over 15 years as a practicing clinician and professor at Children’s Hospital Los Angeles and the Los Angeles County (LAC) and University of Southern California (USC) Medical Center. As a clinician, Dr. Wong presented and published numerous studies and papers on her research in hemophilia and hematology and has served as a reviewer for medical journals including the American Journal of Hematology, Hemophilia and the Lancet. In 2003, Dr. Wong was appointed by the Secretary of Health and Human Services as a member of the Advisory Committee on Blood Safety and Availability. Dr. Wong earned her M.D. at the USC, Keck School of Medicine and a BA at Occidental College. She served a Fellowship at the LAC and USC Medical Center in pediatric hematology-oncology and was appointed Associate Professor of Pediatrics at the University of Southern California. About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application – across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page. View source version on businesswire.com: Contacts Investor Contact: ir@be.bio Source: Be Biopharma, Inc. View this news release online at:

未经授权，不得转载凝血因子Ⅷ的长效缓释温敏型水凝胶的研制Preparation of Long-acting Sustained-release Thermosensitive Hydrogels of Coagulation Factor Ⅷ邹茜茜，郜珍叶，张伟捷，吴 飞，金 拓*(上海交通大学药学院，上海 200240)摘要：凝血因子Ⅷ (F8) 作为治疗血友病常用药物之一，存在半衰期短(10 ～ 14 h) 的缺点，其注射剂需每周多次给药。为获得F8 的长效缓释制剂，该研究通过热开环聚合法得到具反向热敏性质的三嵌段聚合物PLGA-PEG-PLGA 作为温敏水凝胶基质，制备了一种新型长效缓释的温度敏感型水凝胶载F8 制剂，在4 ℃及以下呈溶液，37 ℃附近呈凝胶，并考察了其体外活性及体内外释放行为。结果显示，体外释放试验中，d1 突释了约17.4％的载药量，总共实现了3 周左右的释放，22 d 时F8 的累积释放率达到92％ ；制剂成胶前后F8 活性达到97％以上，且释放过程中释放液中的F8 活性仍能维持在60％以上，提示温敏水凝胶中的F8 能维持稳定。体内释放曲线表明，大鼠在给药后1 h 达到血药浓度峰值，为(113.21±14.50)ng/ml，整个缓释周期内，血药浓度可维持在最低治疗浓度(10 ng/ml) 以上长达15 d。该研究成功开发了一种F8 长效缓释制剂，具有临床应用潜力。关键词：凝血因子Ⅷ；温敏水凝胶；长效缓释以下为文章节选血友病A 一般是由人体内凝血因子Ⅷ ( factor Ⅷ，F8，1) 缺乏或功能障碍引起的X 连锁出血性疾病。1 由2 332 个氨基酸组成，是相对分子质量高达3×105 的蛋白质，其中的1 条重链和1 条轻链通过金属离子维持非共价键连接[1]。目前对血友病A 患者的主要治疗方法是替代疗法，即静脉注射外源的1 使其达到体内正常水平，而1 往往从人血浆中提取纯化或通过重组DNA 技术生产。当前市场上销售的主流重组凝血1 产品有百特国际(Baxter International) 公司的Advate，德国拜耳(Bayer) 公司生产的三代产品，Kogenate、Kogenate FS 以及Kovaltry。这类重组凝血因子在人体内半衰期只有10 ～ 14 h，因此对预防性治疗的血友病A 患者来说，需要隔天注射或每周静脉注射3 次，以维持至少1％的体内活性。这对需要终身给药的患者来说，生理上异常痛苦且顺应性差。目前已有的延长半衰期的手段包括聚乙二醇修饰(PEGylation)、PEG 化脂质体、生成Fc 融合蛋白等[2—3]。N8-GP( 商品名Esperoct) 由诺和诺德公司生产，于2019 年获得FDA 批准。这是一种基于PEG 修饰原理的长效1 制剂，研究表明在患者中的半衰期延长了1.6 ～ 1.9 倍。DUMONT 等构建了一种重组融合蛋白( rF Ⅷ Fc)，在小鼠和狗的动物模型中，发现rF Ⅷ Fc 的半衰期比rF Ⅷ延长了约2倍[4]。目前的长效缓释研究方法中，1 半衰期至多延长至原来的2 倍，延长更长时间的相关研究几乎是空白的。因此，开发一种新型长效缓释的1 制剂有非常大的临床应用潜力和意义。水凝胶具有独特的三维网格结构，可包载活性成分形成药物贮库，而独特的流变性能也使其具备可注射性，可递送药物到人体或组织内的特定部位，达到缓释效果[5]。大多数化学物质遵循溶解度随温度升高而增加的规律。温度敏感型水凝胶反而是在低温下可溶、在高温成胶，具有反向热敏性质，使其可以在人体皮下原位形成凝胶。另外，通过调节聚合物中亲水与疏水链段的比例可以调节水凝胶的相变温度以及降解速度，从而控制药物的缓释周期，是当前研究较多的一种缓释手段[6]。本研究拟制备出一种可以在37 ℃下原位成胶、缓释长达数周的载1 热敏水凝胶，并考察所得该制剂中的药物活性，以及体内外过程中的药物释放行为。采用三嵌段聚合物，即聚乳酸- 羟基乙酸- 聚乙二醇- 聚乳酸- 羟基乙酸(PLGA-PEG-PLGA) 共聚物(2) 作为热敏水凝胶基质。成胶过程如图1 所示，Tgel 是热敏水凝胶的成胶温度，Tbody 是动物的体内温度；当环境温度低于Tgel 时，体系呈溶液状态，制剂具备可注射性，注射至动物皮下后，由于Tbody 高于Tgel，体系成胶。↑长按二维码阅读全文基金项目：国家自然科学基金项目(81872802)作者简介：邹茜茜(1996—)，女，硕士研究生，专业方向：蛋白药物的长效缓释递送系统研究。通信作者：金 拓(1952—)，男，教授，博士，从事生物大分子递药系统的研究。E-mail：tomtjin@gmail.com文章详情欢迎登录《中国医药工业杂志》官网查看。END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001