Clinical antibodies are an important class of drugs for the treatment of both chronic and acute diseases. Their manufacturability is subject to evaluation to ensure product quality and efficacy. One critical quality attribute is deamidation, a non-enzymatic process that is observed to occur during thermal stress, at low or high pH, or a combination thereof. Deamidation may induce antibody instability and lead to aggregation, which may pose immunogenicity concerns. The introduction of a negative charge via deamidation may impact the desired therapeutic function (i) within the complementarity-determining region, potentially causing loss of efficacy; or (ii) within the fragment crystallizable region, limiting the effector function involving antibody-dependent cellular cytotoxicity. Here we describe a transformative solution that allows for a comparative assessment of deamidation and its impact on stability and aggregation. The innovative streamlined method evaluates the intact protein in its formulation conditions. This breakthrough platform technology is comprised of a quantum cascade laser microscope, a slide cell array that allows for flexibility in the design of experiments, and dedicated software. The enhanced spectral resolution is achieved using two-dimensional correlation, co-distribution, and two-trace two-dimensional correlation spectroscopies that reveal the molecular impact of deamidation. Eight re-engineered immunoglobulin G4 scaffold clinical antibodies under control and forced degradation conditions were evaluated for deamidation and aggregation. We determined the site of deamidation, the overall extent of deamidation, and where applicable, whether the deamidation event led to self-association or aggregation of the clinical antibody and the molecular events that led to the instability. The results were confirmed using orthogonal techniques for four of the samples.

Cancer Research Communications

PSGL-1 blockade induces classical activation of human tumor-associated macrophages

作者: Sazinsky, Steve ; Feldman, Igor ; Kauffman, Kevin ; Ries, Carola ; Basinski, Sara ; Nowakowska, Dominika ; Brehm, Michael ; Komoroski, Veronica ; Rooney, Kate ; Wahle, Joseph ; Culyba, Elizabeth K. ; Phennicie, Ryan ; Nguyen, Phuong A. ; Vollmann, Elisabeth H. ; Novobrantseva, Tatiana I. ; O'Nuallain, Brian ; Zafari, Mohammad ; Manfra, Denise

The immune suppressive microenvironment is a major culprit for difficult-to-treat solid cancers.Particularly, inhibitory tumor-associated macrophages (TAM) define the resistant nature of the tumor milieu.To define tumor-enabling mechanisms of TAMs, we analyzed mol. clin. datasets correlating cell surface receptors with the TAM infiltrate.Though P-selectin glycoprotein ligand-1 (PSGL-1) is found on other immune cells and functions as an adhesion mol., PSGL-1 is highly expressed on TAMs across multiple tumor types.SiRNA-mediated knockdown and antibody-mediated inhibition revealed a role for PSGL-1 in maintaining an immune suppressed macrophage state.PSGL-1 knockdown or inhibition enhanced proinflammatory mediator release across assays and donors in vitro.In several syngeneic mouse models, PSGL-1 blockade alone and in combination with PD-1 blockade reduced tumor growth.Using a humanized tumor model, we observed the proinflammatory TAM switch following treatment with an anti-PSGL-1 antibody.In ex vivo patient-derived tumor cultures, a PSGL-1 blocking antibody increased expression of macrophage-derived proinflammatory cytokines, as well as IFNγ, indicative of T-cell activation.Our data demonstrate that PSGL-1 blockade reprograms TAMs, offering a new therapeutic avenue to patients not responding to T-cell immunotherapies, as well as patients with tumors devoid of T cells.

项与 Verseau Therapeutics, Inc. 相关的新闻（医药）

2024-01-16

·Business Wire

NextPoint Therapeutics Appoints Tatiana Novobrantseva, PhD, as Chief Scientific Officer

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- NextPoint Therapeutics , a clinical-stage biotechnology company developing precision immuno-oncology therapeutics targeting the novel HHLA2 pathway, today announced the appointment of Tatiana Novobrantseva, PhD, as Chief Scientific Officer (CSO). Dr. Novobrantseva brings deep knowledge and broad experience in immunology/inflammation, cancer, immuno-oncology, autoimmunity and fibrosis to NextPoint, along with an outstanding record of accomplishment in drug development across immuno-oncology discovery and antibody development. “Tatiana is a star in the immuno-oncology world, and we are thrilled to welcome her to the NextPoint team,” said Detlev Biniszkiewicz, PhD, Chief Executive Officer of NextPoint Therapeutics. “Her strategic leadership and entrepreneurial spirit will be instrumental during this pivotal time for NextPoint’s growth as we advance our precision immuno-oncology programs targeting the HHLA2 pathway.” Dr. Novobrantseva co-founded Verseau Therapeutics in 2017 and served as Chief Scientific Officer for over 5 years, advancing immunotherapies stimulating macrophage repolarization to initiate anti-cancer immune responses, and is currently an Advisor to Verseau. Additionally, Dr. Novobrantseva previously led oncology discovery and development projects at Moderna as Chief Scientific Officer, Immuno-Oncology Research. She serves on the Scientific Advisory Boards of Voro Therapeutics and FairJourney Biologics, as well as on the Advisory Board for the mentorship organization Women in the Enterprise of Science and Technology. After earning a PhD from the University of Cologne in Germany, Dr. Novobrantseva completed postdoctoral research at Harvard Medical School in the laboratory of Dr. Klaus Rajewsky on B cell immunology and autoimmunity. She advanced in industry as a scientist at Biogen and Alnylam Pharmaceuticals. Dr. Novobrantseva then participated in building Jounce Therapeutics as Director of Research, leading programs to reactivate the immune system against cancer, before consulting on a freelance basis on immunological aspects of drug development for various biopharma companies, developing scientific strategies across therapeutic areas for discovery and preclinical development. “NextPoint takes a highly innovative approach to harnessing the immune system to fight cancer, which has been a personal mission of mine for more than a decade,” commented Dr. Novobrantseva. “I am thrilled to build on this exciting approach to deliver novel, precision immuno-oncology therapeutics to patients with currently intractable cancers.” About NextPoint Therapeutics NextPoint is advancing the field of immuno-oncology through its leading scientific work on the novel HHLA2 pathway. Our innovative approach integrates foundational science with a defined clinical biomarker strategy to deliver a new class of monotherapies for patients who do not benefit from PD-1/L1 inhibitors. Our team of proven drug developers is working closely with our renowned scientific founders to launch a new world of precision immuno-oncology. To learn more, visit nextpointtx.com .

高管变更免疫疗法

2022-09-02

·动脉网

【首发】致力于新靶点新药物研发，国内首家聚焦巨噬细胞创新药企美赛生物再次完成数千万融资

动脉网获悉，近日，杭州美赛生物医药科技有限公司宣布完成数千万元的新一轮融资。美赛生物是国内首家专注于肿瘤微环境中巨噬细胞全新靶点的生物药开发的新兴生物技术企业，针对巨噬细胞的药物可以增强巨噬细胞对肿瘤细胞的吞噬，募集和活化下游的效应T细胞，实现肿瘤免疫微环境的重编程，达到治疗甚至是完全治愈实体肿瘤的目的，极大的弥补现有肿瘤治疗药物和治疗手段的不足。本轮融资由聚明创投独家领投，老股东凯风创投持续投资，所募集的资金将主要用于现有新靶点和新产品管线的研发、产品注册和临床申报。肿瘤免疫微环境是实体肿瘤发生和发展的土壤，也决定了肿瘤免疫疗法的效果。大量的研究表明，临床大多数实体肿瘤是T细胞浸润少、巨噬细胞等髓系细胞浸润较多的“冷肿瘤”。肿瘤相关巨噬细胞帮助肿瘤逃避免疫系统的识别、抑制T细胞的杀伤肿瘤活性、甚至还能协助形成物理屏障，抑制T细胞的浸润。目前国际上包括Pheast Therapeutics、Verseau Therapeutics多家新兴生物技术企业开始布局巨噬细胞新靶点，并获得巨额的早期投资。美赛生物作为国内新兴生物技术企业，从基础科学的源头创新出发，致力于研发巨噬细胞新靶点与新药物，在巨噬细胞新靶点领域处于领先地位。美赛生物创始人兼CEO袁红博士表示：“感谢聚明创投对美赛生物团队的认可。目前国内从事源头创新的生物医药企业还较为稀缺，美赛生物从创立伊始，就坚持原创的肿瘤免疫理论创新，专注于巨噬细胞新靶点的发现和新机制验证，基于“肿瘤免疫微环境重编程”理论研发全新的抗肿瘤药物，弥补PD-1阻断剂等药物响应率低等问题。目前我们的部分新靶点的候选药物治疗已在实验动物上看到了肿瘤消退和治愈，部分研发产品进入成药性评价阶段，我们非常期待这些产品在下一个阶段进入临床申报，早日实现临床转化，造福全球患者。”聚明创投合伙人时永灵博士表示：“以PD-1为代表的肿瘤免疫治疗药物开创了肿瘤治疗的新时代，但也存在响应率低及多个适应症开发失败的不足，肿瘤免疫新靶点药物的研发有望拓展肿瘤免疫治疗的边界。美赛生物团队致力于巨噬细胞全新靶点的发现及对应的新药研发，创始团队拥有10多年相关基础研究及产业化经验，项目执行效率高，已构建了完备的靶点发现、机制研究、药物发现、成药性评价及CMC平台，取得了多个创新性发现及药物研发阶段性成果。聚明创投很高兴有机会在早期助力美赛生物发展，我们坚信公司未来能在巨噬细胞肿瘤免疫领域取得突破性进展，解决未满足临床需求，惠及更多的肿瘤患者。”凯风创投管理合伙人黄昕博士表示：“ 以PD1，CD47为代表的肿瘤免疫靶点在国内的开发现状，表明了基于创新机制驱动的新靶点药物研发仍然是业界追逐的目标。美赛生物团队具备国际原创的科学发现能力，深刻的生物学探究功底，加上在产业转化上丰富成熟的经验，有望产生真正意义上的First-in-class的药物。我们凯风创投很高兴继续加码美赛生物，支持原创机制发现到工业转化，从而解决临床上的未满足需求，惠及广大患者。”关于聚明创投聚明创投聚焦于生命科学领域的早期风险投资，自2018年创立至今已累计投资40余家涵盖创新药、生物技术、医疗器械（含诊断）领域的创业企业。聚明创投始终立足中国面向全球的临床痛点，专注于与优秀企业同行，提供全方位服务，陪伴企业成长。关于凯风创投凯风创投是一家专注于早期科技型企业投资的中美双币风险投资机构，提倡平等、透明、分享、创新的团队文化。公司成立于2009年，重点关注医疗健康和IT硬科技领域，管理规模累计超50亿元人民币，先后为一百多个优秀团队和项目提供资金和资源支持。凯风创投助力康乃德生物医药（NASDAQ: CNTB）、Thrive（NASDAQ: EXAS）、旭创科技（300308）、敏芯股份（688286）、华兴致远（000008）、奥联电子（300585）等10余家高科技企业成功上市，同时赋能太美医疗科技、臻和科技、华科精准、创鑫激光等一大批企业在各自细分领域脱颖而出。想要联系动脉网报道的企业，请点击文末左下方“阅读原文”填写表单，我们的工作人员将征求企业意见后，尽快为您服务。左右滑动查看更多近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

创新药免疫疗法抗体First in Class

2022-03-23

·医药观澜

速递！三生国健引进的抗PSGL-1抗体获批临床

3月22日，中国国家药监局药品审评中心（CDE）官网公示，三生国健申报的SSGJ-617注射液获得临床试验默示许可，拟定适应症为晚期实体瘤。根据三生国健新闻稿，SSGJ-617是由Verseau Therapeutics公司研发的一款以PSGL-1为靶标的拮抗型抗体，三生国健拥有其大中华区权益。本次获批临床后，三生国健将于近期开展该药的1期临床试验。以PD-1抑制剂为代表的免疫疗法已经造福了很多患者，然而仍有部分患者无法从这类疗法中获益。Verseau公司正在通过开发巨噬细胞检查点调节剂（MCM）来扩大免疫治疗的受益范围（约75%的人类癌症中都有巨噬细胞），希望使癌症、免疫类和炎症类疾病患者受益。该公司开发的MCM调节剂能够根据疾病情况将巨噬细胞重新编程，使其更具致炎症性或耐受性，并激活包括T细胞在内的多种免疫细胞类型。其中，P-选凝素糖蛋白配基-1（PSGL-1）靶点是Verseau公司正在开发的巨噬细胞检查点调节剂管线中首个进入开发阶段的靶标。它是一种粘附分子，参与响应组织损伤或炎症的免疫细胞运送。通过特定表位与PSGL-1结合会触发巨噬细胞复极化，而不会影响选择素和VISTA介导的PSGL-1功能。SSGJ-617则充当了一种自然生物开关，将免疫抑制性M2型巨噬细胞转化为促炎、抗肿瘤发生的M1型巨噬细胞。这些M1型巨噬细胞启动免疫反应，吸引并激活肿瘤微环境中的抗肿瘤免疫细胞。与PD-1抑制剂疗法相比，SSGJ-617抗体能表现出更大的促炎症反应，刺激免疫应答。 2019年，三生制药宣布从Verseau公司获得了这款PSGL-1靶点在研单抗药物的大中华区独家授权。根据协议，三生制药将获得在大中华区的独家许可，开发和商业化一系列适用于所有人类肿瘤适应症的巨噬细胞检查点调节剂抗体。针对首个授权项目SSGJ-617（VTX-0811），三生制药子公司三生国健将负责大中华区的开发和商业化。据悉，此前Verseau公司就该药物在美国的IND申请已获FDA批准，将于2022年第一季度启动治疗实体瘤的1a/1b期临床研究。而该药本次在中国获批临床后，三生国健将于近期开展该药的1期临床试验。三生国健董事长娄竞博士表示：“很高兴SSGJ-617获NMPA批准开展1期临床试验。SSGJ-617是一款潜在‘first-in-class’的巨噬细胞免疫检查点抑制剂，具有创新的靶点和机制，同时SSGJ-617也是我们与Verseau公司合作的首款创新药，其在美国临床试验的顺利开展也将更好地助推该药在中国的开发进程，推进药物早日上市，造福病患。” 参考资料： [1]中国国家药监局药品审评中心（CDE）官网.Retrieved Mar 23，2022.From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2] 三生国健抗PSGL-1抗体SSGJ-617获NMPA批准开展治疗晚期实体瘤I期临床试验.Retrieved Mar 22，2022.From https://mp.weixin.qq.com/s/7LwzOhOKZqUSmAAw1568Pg [3]三生国健合作伙伴美国Verseau公司抗PSGL-1单抗VTX-0811 IND申请获FDA批准.Retrieved Jan 11，2022.From https://mp.weixin.qq.com/s/JmSCRBezZhkyWj7vYO_8Pw 内容来源于网络，如有侵权，请联系删除，谢谢

抗体免疫疗法创新药First in Class合作

100 项与 Verseau Therapeutics, Inc. 相关的药物交易

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100 项与 Verseau Therapeutics, Inc. 相关的转化医学

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药物(靶点)	适应症	全球最高研发状态

VTX-1619	炎症更多	临床前
SiRNA immune disoder therapeutics(Verseau Therapeutics, Inc.)	免疫系统疾病更多	临床前
Anticancer therapeutics(Verseau Therapeutics, Inc.)	肿瘤更多	临床前
SiRNA oncology therapeutics(Verseau Therapeutics, Inc.)	肿瘤更多	临床前
VTX-0811 ( PSGL-1 )	实体瘤更多	无进展