A Randomized, Placebo-Controlled, Phase 2 Study of HB-101, a Bivalent Cytomegalovirus (CMV) Vaccine, in CMV-Seronegative Recipient (R-) Patients Awaiting Kidney Transplantation from Living CMV-Seropositive Donors (D+)

开始日期2019-05-23

申办/合作机构

Hookipa Biotech AG

NCT03629080 / Completed临床2期

HB-101 is a bivalent recombinant vaccine against human CMV infection. This is a randomized, placebo-controlled, phase 2 study to assess the safety, reactogenicity, immunogenicity, and efficacy of HB-101 in CMV-Seronegative patients receiving a kidney transplant from a CMV-Seropositive living donor and CMV-Seropositive patients.Patients enrolled should have a living donor kidney transplantation ideally planned between two to four months after the first injection of study drug (HB-101 or placebo).

开始日期2018-12-12

申办/合作机构

Hookipa Biotech AG

NCT02798692 / Completed临床1期

Randomized, Placebo-controlled, Double-blind Phase I Dose-escalating Trial to Evaluate the Safety and Immunogenicity of a Vaccine Against Human Cytomegalovirus

The objectives of this first-in-human is to evaluate the safety and the immunogenicity of three administrations of a bivalent vaccine candidate against human cytomegalovirus, at three different dose levels.

开始日期2016-06-01

申办/合作机构

Hookipa Biotech AG

100 项与 HB-101 相关的临床结果

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100 项与 HB-101 相关的转化医学

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100 项与 HB-101 相关的专利（医药）

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项与 HB-101 相关的文献（医药）

2022-04-19·The Journal of infectious diseases2区 · 医学

A Randomized Dose-Escalating Phase I Trial of a Replication-Deficient Lymphocytic Choriomeningitis Virus Vector-Based Vaccine Against Human Cytomegalovirus

2区 · 医学

Article

作者: Bruhwyler, Jacques ; De Vos, Beatrice ; Buchinger, Heidemarie ; Schwendinger, Michael ; Monath, Thomas P ; Ganeff, Corinne ; Pinschewer, Daniel D ; Huygens, Ariane ; Leroux-Roels, Geert ; Lilja, Anders E ; Orlinger, Klaus K ; Thiry, Georges

Abstract:

Background:

A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection.

Methods:

HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Safety and immunogenicity were the respective primary and secondary endpoints. Subjects were followed for 12 months after the initial immunization.

Results:

Vaccination was associated with transient mild to moderate adverse events. HB-101 administration induced dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. Two administrations were sufficient to elicit dose-dependent gB-binding and cytomegalovirus-neutralizing antibodies (Abs). Cytomegalovirus-specific immune responses were boosted after each administration. Only 1 of 42 vaccine recipients mounted a transient LCMV vector-neutralizing Ab response.

Conclusions:

HB-101 was well tolerated and induced cytomegalovirus-specific polyfunctional CD8 T-cell and neutralizing Ab responses in the majority of subjects. Lack of vector-neutralizing Ab responses should facilitate booster vaccinations. These results justify further clinical evaluation of this vaccine candidate.

2011-10-01·Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas4区 · 医学

Typical and atypical enteropathogenic Escherichia coli bacterial translocation associated with tissue hypoperfusion in rats

4区 · 医学

ArticleOA

作者: Gomes, T.A.T. ; Menchaca-Diaz, J.L. ; Liberatore, A.M.A. ; Koh, I.H.J. ; Moreira, F.C.

Although enteropathogenic Escherichia coli (EPEC) are well-recognized diarrheal agents, their ability to translocate and cause extraintestinal alterations is not known. We investigated whether a typical EPEC (tEPEC) and an atypical EPEC (aEPEC) strain translocate and cause microcirculation injury under conditions of intestinal bacterial overgrowth. Bacterial translocation (BT) was induced in female Wistar-EPM rats (200-250 g) by oroduodenal catheterization and inoculation of 10 mL 10(10) colony forming unit (CFU)/mL, with the bacteria being confined between the duodenum and ileum with ligatures. After 2 h, mesenteric lymph nodes (MLN), liver and spleen were cultured for translocated bacteria and BT-related microcirculation changes were monitored in mesenteric and abdominal organs by intravital microscopy and laser Doppler flow, respectively. tEPEC (N = 11) and aEPEC (N = 11) were recovered from MLN (100%), spleen (36.4 and 45.5%), and liver (45.5 and 72.7%) of the animals, respectively. Recovery of the positive control E. coli R-6 (N = 6) was 100% for all compartments. Bacteria were not recovered from extraintestinal sites of controls inoculated with non-pathogenic E. coli strains HB101 (N = 6) and HS (N = 10), or saline. Mesenteric microcirculation injuries were detected with both EPEC strains, but only aEPEC was similar to E. coli R-6 with regard to systemic tissue hypoperfusion. In conclusion, overgrowth of certain aEPEC strains may lead to BT and impairment of the microcirculation in systemic organs.

2011-01-01·Biosensors & bioelectronics1区 · 工程技术

High-throughput microfluidic system for long-term bacterial colony monitoring and antibiotic testing in zero-flow environments

1区 · 工程技术

Article

作者: Jinyi Wang ; Peng Sun ; Peng Chen ; Qin Tu ; Jun Sha ; Zhiyun Zhang ; Yang Liu

In this study, a high-throughput microfluidic system is presented. The system is comprised of seven parallel channels. Each channel contains 32 square-shaped microchambers. After simulation studies on samples loaded into the microchambers, and the solute exchange between the microchambers and channels, the long-term culture of Escherichia coli (E. coli) HB101 in the microchambers is realized. Using the principle that L-arabinose (L-Ara) can induce recombinant E. coli HB101 pGLO to synthesize green fluorescent protein (GFP), the real-time analysis of GFP expression in different initial bacterial densities is performed. The results demonstrate that higher initial loading densities of the bacterial colony cause bacterial cell to enter log-phase proliferation sooner. High or low initial loading densities of the bacterial cell suspension induce the same maximum growth rates during the log-phase. Quantitative on-chip analysis of tetracycline and erythromycin inhibition on bacterial cell growth is also conducted. Bacterial morphology changes during antibiotic treatment are observed. The results show that tetracycline and erythromycin exhibit different inhibition activities in E. coli cells. Concentrations of 3 μg/mL tetracycline can facilitate the formation of long filamentous bacteria with the average length of more than 50 μm. This study provides an on-chip framework for bacteriological research in a high-throughput manner and the development of recombinant bacteria-based biosensors for the detection of specific substances.

项与 HB-101 相关的新闻（医药）

2024-01-31

·生物制药小编

被高瓴清仓，被罗氏退货

同时被资本和大药厂抛弃是什么体会，HOOKIPA Pharma可能深有体会。近日（1月29日），沙粒病毒公司HOOKIPA Pharma更新了自己的业务重点和合作项目信息，其中提到，罗氏决定单方面终止HOOKIPA在KRAS变异癌症中的HB-700项目的合作和许可协议。无独有偶，高瓴资本旗下专注于二级市场投资的HHLR在2023年Q3清仓了才建仓一季度的HOOKIPA Pharma。也许是受到了罗氏“退货”的影响，HOOKIPA将裁员约30%。受此消息影响，该公司股价截止1月29日收盘时跌去了10%，而事实上，从2022年末以来，这家公司一直都在1美元股价的底部徘徊，如今股价已经不足0.7美元，已经处于退市边缘。这家本该是诺奖得主参与的明星公司怎么会落到如今的田地？明星技术不能转化为有效临床从技术来看，采用沙粒病毒相比于传统的溶瘤病毒确实是具有以下所列的优势，但很显然该公司并没有将理论优势转化为实际临床优势。①没有靶向性限制：传统的溶瘤病毒因为肿瘤内存在IFN-I（I型干扰素）而有限制性地复制，肿瘤靶向选择有所限制，而被感染肿瘤细胞溶解也可能导致病毒受限。但沙粒病毒科中的非致细胞病变的淋巴细胞性脉络丛脑膜炎病毒（LCMV）却不同，能够感染广泛的宿主细胞。②持久性：沙粒病毒的持久性优秀，感染细胞后除非被CD8+ T细胞溶解，否则它会在长寿的宿主细胞中持续存在。③诱导T细胞免疫激活：artLCMV能够重塑肿瘤免疫微环境（TME），它能够在TME中表达趋化因子Cxcl13的mRNA，从而产生Cxcl13表达的成纤维基质细胞（FSC），而这种FSCs亚群中能够显著刺激免疫并诱导细胞因子IL-33产生。而IL-33正是肿瘤免疫微环境中的关键因子，能够激发CD8+ T细胞的肿瘤免疫活性。而这种技术运用在传染病治疗上的原理也和肿瘤中的原理类似，同样是加强CD8+ T细胞。而到传染病这一领域LCMV的另外一个优势是由于载体的聚糖屏蔽包膜蛋白，因此即使在多轮接种后，人体内也几乎不存在载体诱导的中和抗体(nAbs)，可以做到重复给药，而不会引起显著的抗载体抗体免疫。首个人体临床数据即将发布，高管竟然减持如果从HOOKIPA的股价来看，转折点似乎出现在2021年5月，那之后这家公司的股价再也没有高于10美元过。当时该公司宣布将参与了2021年6月的ASCO，并在那里发布首个临床数据。但奇怪的是，本应该是即将证明自己的好机会，该公司多名高管竟然齐刷刷减持，这一后果当然影响到了市场，当时股价更是从一个月内蒸发了50%。临床设计是否有问题？后来6月披露看似很好的ASCO数据也同样包藏隐患，虽然说是HB-201治疗HPV16+癌症患者的1期试验显示T细胞的免疫应答突出，效果似乎优于标准二线疗法，二线头颈癌的ORR有18%，中位PFS有3.45个月。但是值得指出的是，HB-201/202入组患者可能有相当多接受K药治疗后的患者，然而这一隐藏的数据似乎并没有披露具体数据，因此并不清楚到底这优于标准二线疗法的效果到底是K药贡献的还是HB-201贡献的。而且临床设计方面也没有将HB-201/202+K药与K药单用做对照组对比。实际上并不能证明HB-201/202+K药与K药相比就有统计学上的意义。虽然后续该公司又去找默沙东合作，开发HB-201/202+K药在一二线头颈癌的临床，但这多少有些晚了，跌去的股价和失去的信心回不来了。直到去年的一线治疗数据披露之后，才给了HB-201/HB-202一线希望，HB-200（201和202）联合pembrolizumab治疗的19名可评估患者的确认客观缓解率（ORR）为42%，疾病控制率（DCR）为74%，是K药单独治疗的19% ORR的两倍。抗病毒疗法有效性存疑同样出现问题的还有抗病毒治疗，此前该公司的巨细胞病毒疫苗HB-101临床失败，作为最领先的管线，在抗病毒治疗过程中毫无效果。那么这家公司和吉利德的两项抗病毒临床前合作也被打上了个问号，更何况其中一款的适应症还是最难开发的HIV疫苗，或许只有HBV疫苗拥有一线生机。虽然吉利德在去年年末股权投资了该公司，但是该公司的重点业务现在也是在肿瘤上。还未IND就遭退货现在针对KRAS的沙粒病毒疫苗HB-700也被罗氏退货。这项2022年签订，价值9.9亿美元的合作，甚至到现在被退货的时候竟然还停留在临床前阶段……如下图该公司管线图及预期里程碑所示，该公司本来预期HB-700在2024年第一季度IND，竟然成了2024年第一季度被买家退货，多少有些讽刺了。总结从技术上来说，虽然HOOKIPA Pharma沾上了诺奖的明星光环，但最终不免褪去层层包裹的包装，回归普通Biotech公司正确的位置上。参考来源：Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner 1, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist, and Daniel D. Pinschewer (2022). Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis. Int. J. Mol. Sci. 2022, 23(5), 2700. International Journal of Molecular Scienceshttps://www.hookipapharma.com/our-programs/our-pipeline/

ASCO会议免疫疗法

2024-01-30

·药时代

诺奖得主背书的Biotech被罗氏“退货”，停管线，裁员30%，股价大跌10%……

退货15个月后，HOOKIPA Pharma宣布已收到罗氏的通知，决定终止双方就项目HB-700的合作和许可协议，执行时间为 2024 年 4 月 25 日。在此之前，HOOKIPA表示已满足协议的所有推进标准，并且仍然有资格获得与IND提交相关的最终里程碑付款。HB-700是一款在研沙粒病毒免疫疗法，同时靶向多种KRAS突变，覆盖肺癌、结肠癌等其他癌症。2022年10月20日，罗氏以2500万美元首付款、9.3亿美元里程碑金额以及一定比例的销售分成引进该产品。根据当时协议，Hookipa负责临床前开发以及早期临床，1b期转给罗氏。值得注意的是，在当初的协议中罗氏还有权通过增加一个新的候选产品来扩大合作，HOOKIPA将在行使期权中获得1500万美元的额外付款。而如今，面对即将破裂的合作，Hookipa能做的只有加速推进IND，拿到最后一笔钱。裁员/停管线美东时间1月29日，HOOKIPA 更新了业务重点与合作伙伴计划。上文的罗氏“退货”不过是业务调整中的一部分。目前，HOOKIPA将研发重心放在HB-200、HB-400与HB-500上。HB-200已推进至临床2期，正在1线和2线治疗中与K药联合使用，治疗复发性/转移性HPV16+头颈癌患者，并单独作为护理后标准治疗。根据2023年欧洲肿瘤内科学会大会上公布的（NCT04180215）数据显示，19例（HNSCC，CPI-naïve）患者的ORR为42%，是单药使用K药的历史ORR（19%）的一倍。至于HB-400与HB-500两个项目，早在2018年，吉利德便与HOOKIPA就此达成合作。根据当时协议，前者将预付1000万美元并将资助两个项目所有研发活动。HB-400是一款在研治疗性乙肝疫苗，2023年5月完成首例受试者给药，该项目的临床开发工作由吉利德主导。HB-500是一款在研治疗性HIV疫苗，2023年11月获批IND，预计2024上半年达成下一个里程碑。锚定管线重心之后（合作开发产品），HOOKIPA暂时搁置自研产品HB-300，以节省资金，确保管道的成功和运营效率。节省资金第一步，暂停自研管线HB-300。HB-300是一款针对前列腺癌沙粒病毒产品，于2022年7月获批IND，用于治疗转移性去势抵抗性前列腺癌。值得一提的是，2023年3月HOOKIPA进展最快的自研管线HB-101（一款二价的巨细胞病毒疫苗）宣告2期临床失败后，便停掉了该管线，其股价便长期徘徊在1美元以下。2024年1月29日，HOOKIPA股价，盘后大跌10%节省资金第二步，裁员。根据HOOKIPA新闻稿显示，后续公司将裁员30%，并根据公司项目的新优先级重新平衡其成本结构。截至2023年12月31日，HOOKIPA还拥有1.175亿美元现金流，用于后期开发支出。（2023年11月，HOOKIPA获得了吉利德2125万美元的股权融资，吉利德以每股1.4167美元的价格购买了1500万股新发行的普通股。）诺奖得主背书作为科学界最具含金量的诺贝尔奖，任何一位得主的诞生，无不意味着等多的资源倾斜。而HOOKIPA的联合创始人Rolf Zinkernagel博士正是一位诺贝尔奖得主。因其基于沙粒病毒的研究CD8+ T细胞如何识别病毒感染的细胞而获得了1996年诺贝尔生理学或医学奖。在自然界中，因为沙粒病毒会引发仅针对病毒本身的免疫反应，故被长期用作研究T细胞反应的临床前工具。Rolf Zinkernagel则提出了工程化沙粒病毒，通过重新设计沙粒病毒，使其能引起相同高水平的T细胞反应，量身定制（tailored）针对特定疾病的有效免疫应答，来靶向疾病进行治疗，也就是如今HOOKIPA的药物开发基础。如今，即便是诺奖得主创立的公司也在时代洪流的冲刷下，隐隐有消声遗迹之势。Springer在2015年出版的《为什么伟大不能被计划》一书中提及，“有时候，实现“宏图大志”的最佳方法，便是“不刻意追求某个特定志向”。就像是诺贝尔奖，其引领的并非是具体目标的未来发展，而是当一个领域的基础原理有了突破之后，使其成为一个时代的兴起的契机之一。参考资料：1.HOOKIPA Pharma官网2.诺贝尔奖官网3.失败了，一款基于沙粒病毒载体的巨细胞病毒疫苗（佰傲谷BioValley）4.《为什么伟大不能被计划》5.其他公开资料封面图来源：123rf金凯生科“20cm”涨停，司美格鲁肽口服版带动减肥药概念拉升！全球CDMO巨头Lonza将关闭广州工厂，裁员300人。好消息是CDMO企业销售额纷纷增长！GLP-1RA类药物迈入口服时代！诺和忻®（司美格鲁肽片）在中国获批点击阅读原文，查看更多精彩内容

免疫疗法临床2期临床申请疫苗引进/卖出

2023-09-06

·GlobeNewswire-Health Care

HOOKIPA Pharma to participate in upcoming investor conferences in September

NEW YORK and VIENNA, Austria, Sept. 06, 2023 (GLOBE NEWSWIRE) -- HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, today announced that HOOKIPA’s management team will participate in and present at the following upcoming investor conferences: Morgan Stanley Global Healthcare Conference, September 11-13, New YorkFireside Chat: Monday, September 11, 3:35pm ET H.C. Wainwright Global Investment Conference, September 11-13, New YorkFireside Chat: Tuesday, September 12, 11:30am ET In addition to the presentations, HOOKIPA will also host one-on-one investor meetings. About HOOKIPAHOOKIPA Pharma Inc. (NASDAQ: HOOK) is a clinical-stage biopharmaceutical company focused on developing novel immunotherapies, based on its proprietary arenavirus platform, which are designed to mobilize and amplify targeted T cells and thereby fight or prevent serious disease. HOOKIPA’s replicating and non-replicating technologies are engineered to induce robust and durable antigen-specific CD8+ T cell responses and pathogen-neutralizing antibodies. HOOKIPA’s pipeline includes its wholly owned investigational arenaviral immunotherapies targeting Human Papillomavirus 16-positive cancers, prostate cancers, and other undisclosed programs. HOOKIPA is collaborating with Roche on an arenaviral immunotherapeutic for KRAS-mutated cancers. In addition, HOOKIPA aims to develop functional cures of HBV and HIV in collaboration with Gilead. Find out more about HOOKIPA online at www.hookipapharma.com. Forward Looking Statements Certain statements set forth in this press release constitute “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by terms such as “believes,” “expects,” “plans,” “potential,” “would” or similar expressions and the negative of those terms. Such forward-looking statements involve substantial risks and uncertainties that could cause HOOKIPA’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including HOOKIPA’s programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, HOOKIPA’s ability to successfully establish, protect and defend its intellectual property, risks relating to business interruptions resulting from public health crises, the impact of public health crises on the enrollment of patients and timing of clinical results, and other matters that could affect the sufficiency of existing cash to fund operations. HOOKIPA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see HOOKIPA’s quarterly report on Form 10-Q for the quarter ended June 30, 2023, which is available on the SEC’s website at www.sec.gov and HOOKIPA’s website at www.hookipapharma.com. Investors and others should note that we announce material financial information to our investors using our investor relations website (https://ir.hookipapharma.com/), SEC filings, press releases, public conference calls and webcasts. We use these channels, as well as social media, to communicate with our members and the public about our company, our services and other issues. It is possible that the information we post on social media could be deemed to be material information. Therefore, we encourage investors, the media, and others interested in our company to review the information we post on the U.S. social media channels listed on our investor relations website. For further information, please contact: Media InvestorsInstinctif Partners Reinhard Kandera, Chief Financial Officerhookipa@instinctif.com IR@hookipapharma.com+44 (0) 7457 2020

免疫疗法

100 项与 HB-101 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
巨细胞病毒感染	临床2期	美国	Hookipa Biotech AG	2018-12-12
巨细胞病毒感染	临床2期	丹麦	Hookipa Biotech AG	2018-12-12
巨细胞病毒感染	临床2期	法国	Hookipa Biotech AG	2018-12-12
巨细胞病毒感染	临床2期	德国	Hookipa Biotech AG	2018-12-12
巨细胞病毒感染	临床2期	挪威	Hookipa Biotech AG	2018-12-12
巨细胞病毒感染	临床2期	英国	Hookipa Biotech AG	2018-12-12

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03629080 (CTgov)	临床2期	巨细胞病毒感染	83	HB-101 vaccine (HB-101 Vaccine Preemptive)	壓願鏇廠構願鑰範憲餘(獵選醖蓋鬱餘觸夢艱繭) = 築夢獵積顧顧網選壓鑰獵襯願願膚積遞簾遞膚 (獵製糧構顧選淵願壓衊, 餘窪範積艱糧築簾襯醖 ~ 願糧膚鹹顧鏇構夢糧窪) 更多	-	2023-10-26
				placebo (Placebo Preemptive)	壓願鏇廠構願鑰範憲餘(獵選醖蓋鬱餘觸夢艱繭) = 鏇鬱製顧蓋製繭壓齋衊獵襯願願膚積遞簾遞膚 (獵製糧構顧選淵願壓衊, 觸齋襯窪遞築淵餘齋壓 ~ 網襯遞鏇鬱鹽範簾網衊) 更多
NCT03629080 (GlobeNewswire) 人工标引	临床2期	巨细胞病毒感染	80	HB-101	鹹膚願齋齋鏇蓋齋膚鹹(窪廠獵餘鑰鹹夢觸糧窪) = 憲艱鏇鬱繭夢鑰製鏇艱簾鹽齋築選夢壓齋餘鹽 (醖遞壓膚蓋鑰觸築繭範 ) 更多	积极	2021-11-09
				Placebo	-
NCT02798692 (Pubmed \| Am J Trop Med Hyg) 人工标引	临床1期	巨细胞病毒感染	54	HB-101	獵襯齋廠遞遞壓鏇蓋築(衊餘膚觸簾鑰簾憲選夢) = dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. 積廠積顧簾鏇積醖製憲 (鏇範簾齋壓網積壓鹽繭 ) 更多	积极	2020-04-21