A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Doses of Orally Administered DF-006 in Chronic Hepatitis B Patients

开始日期2023-07-19

申办/合作机构-

ACTRN12621000592842 / Completed临床1期

A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After a Single Dose and Multiple Doses of Orally Administered DF 006 in Healthy Subjects (Part 1 and Part 2)

开始日期2021-07-16

申办/合作机构-

CTIS2023-504288-18-00 / Not yet recruiting

- DF-006-1001

开始日期-

申办/合作机构

浙江药苑生物科技有限公司

100 项与 DF-006 相关的临床结果

登录后查看更多信息

100 项与 DF-006 相关的转化医学

登录后查看更多信息

100 项与 DF-006 相关的专利（医药）

登录后查看更多信息

项与 DF-006 相关的文献（医药）

2023-01-01·Hepatology (Baltimore, Md.)

Alpha‐kinase 1 (ALPK1) agonist DF‐006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B

Article

作者: Tuerdi, Aimaier ; Liu, Danyang ; Wei, Yuning ; Yogaratnam, Jeysen ; Dang, Huaixin ; Wei, Xiong ; Pan, Yanfang ; Chen, Juanjuan ; Zhou, Qiong ; Xu, Cong ; Xu, Tian ; Fan, Jieqing ; Yousif, Ashraf Siddig ; Lichenstein, Henri

Background and Aims::

In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha‐kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF‐κB pathway and stimulates innate immunity. Here we characterized the preclinical anti‐HBV efficacy of DF‐006, an orally active agonist of ALPK1 currently in clinical development for CHB.

Approach and Results::

In adeno‐associated virus (AAV)‐HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF‐006. In the mouse models, DF‐006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 μg/kg, 1 μg/kg, and 5 μg/kg, respectively. DF‐006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF‐006 also showed anti‐HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF‐006, there was upregulation of NF‐κB‐targeted genes that are involved in innate immunity.

Conclusion::

DF‐006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF‐006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti‐HBV efficacy by DF‐006.

1987-10-01·The Journal of allergy and clinical immunology1区 · 医学

The prevalence of indoor allergens in the Baltimore area: House dust-mite and animal-dander antigens measured by immunochemical techniques

1区 · 医学

Article

作者: P.S. Norman ; P. Lind ; B. Schwartz ; M. Newton ; H. Løwenstein

Mattress dust samples from 42 homes in Baltimore, Md., were analyzed by ELISA and rocket immunoelectrophoresis (RIE) for major excrement allergens (P1 [equal to Dp 42], Df 6, and Dm 6) of house dust mites, Dermatophagoides pteronyssinus, D. farinae, and D. microceras, by RIE for cat major epithelial allergen (cat Ag 1) and horse major epithelial antigen (horse Ag 11), and by counter-current immunoelectrophoresis (CCIE) for cat and dog antigens. Dp 42 was detected by ELISA in 24 samples (57%) and Df 6 in 39 samples (92%). All samples were negative to Dm 6. Recorded levels varied from 50 ng of allergen per gram of dust (detection limit) to 15,000 ng/gm. A combined content of Dp 42 and Df 6 greater than 700 ng/gm was associated with a positive reaction in RIE. Concentrations of Dp 42 and Df 6 did not correlate (rS = 0.21; p greater than 0.05). Cat and dog antigens were frequently detected by CCIE (77% and 63%, respectively). CCIE titer to cat correlated well with quantitation of cat Ag 1 by RIE (p less than 0.01). Horse antigen was detected in few homes (5%). None of the specific allergen determinations correlated with levels of human serum albumin determined by RIE.

1985-01-01·International archives of allergy and applied immunology

Relationship between Specific Circulating IgE, Basophil Cell-Bound IgE and Histamine Release Induced by Purified Allergens of <i>Dermatophagoides Farinae</i>

Article

作者: Rabillon, J. ; Weyer, A. ; David, B. ; Dandeu, J.P. ; Le Mao, J.

In this study we analysed the presence and proportions of IgE specific for Df 6 and Df 11 two purified allergens of Dermatophagoides farinae. The characterisation of serum IgE and cell-bound IgE for 3 D. farinae-sensitive patients were performed by CRIE, RAST and PRIST assays. Furthermore the basophils from these same patients were studied by histamine release assays in the presence of Df 6 and Df 11. All the individual patient’s cell and serum IgE samples displayed the presence of IgE antibodies specific for Df 6 and Df 11 but the relative quantities of the IgE for these two specificities were characteristic of each patient. The ratios (Specific IgE for Df 11): (Specific IgE for Df 6) (ratio 11:6) were similar in the serum and on the cells for an individual patient. As judged by histamine release assays, the basophil sensitivities towards Df 6 and Df 11 were very different from one atopic patient to another. Moreover cell sensitivities reflected the proportion of Df 6- and Df 11-specific IgE antibodies found in the serum and in the cell eluate.

项与 DF-006 相关的新闻（医药）

2024-05-06

·药渡

进展！药物牧场慢乙肝免疫调节剂DF-006将为2024年欧洲肝脏研究协会大会作最新突破研究壁报展示

-中国上海美国康涅狄格州-以正向遗传学结合人工智能技术，致力于从靶点发现到原创新药（first-in-class）开发的生物科技公司药物牧场日前宣布，公司自主研发的DF-006免疫调节剂1b期实验（ACTRN12621000592842）的慢性乙型肝炎患者数据即将在2024年6月欧洲肝脏研究协会（EASL）会议上做最新突破研究壁报展示。（最新突破研究壁报展示: 一项 1 期、双盲、随机、安慰剂对照、多中心全球研究，评估 DF-006 在慢性乙型肝炎、病毒学抑制患者中的安全性、耐受性和抗病毒活性）DF-006是一种首创的口服ALPK1激动剂免疫调节剂，可有效刺激肝脏中的局部先天免疫[1]。DF-006目前已成功完成健康志愿者单次和多次递增剂量（MAD）评估，以及病毒学抑制的HBeAg阴性慢性乙型肝炎（CHB）患者的多次递增剂量评估。新西兰奥克兰大学医学教授、奥克兰医院首席肝病学家、移植医师兼新西兰肝移植科副主任爱德华·甘恩（Ed Gane）博士评价道：“目前尚无有效治愈慢乙肝（CHB）的方法。DF-006具有一种新的作用机制，能够刺激人体自身的免疫系统，帮助清除感染。作为一种每周给药一次的口服药物，DF-006有可能成为HBV联合治疗方案的首选免疫调节剂。”药物牧场首席医学官Jeysen Yogaratnam博士说：“DF-006在临床前研究中已经显示出有效的抗病毒反应，包括抑制共价闭合环状DNA（cccDNA）和T细胞募集。这项1b期研究的数据为一种新作用机制的药物提供了临床支持，该药物可用于帮助治愈慢乙肝（CHB）患者。”参考文献：1. Xu C, et al. Hepatology. 2023 Jan 1;77(1):275-289. doi: 10.1002/hep.32614. Epub 2022 Sep 17关于药物牧场药物牧场是一家致力于从靶点发现到原创新药（first-in-class）开发的生物科技公司，聚焦开拓乙肝、癌症、心脏和肾病以及ROSAH综合征等自身免疫性疾病的创新疗法。药物牧场独有的IDInVivo+平台结合遗传学和人工智能的突破性技术来发现新的治疗方法，可以在免疫系统健全的模式动物中直接挑选基因靶标。利用IDInVivo+平台，药物牧场已经发现多个全新先天免疫通路和靶点，目前正快速推进多个原创新药进入临床开发。网址：www.drug-farm.com

临床1期临床2期

2024-05-06

·医药观澜

入选最新突破研究壁报，药物牧场将公布慢性乙肝新药临床数据

▎药明康德内容团队编辑近日，药物牧场（Drug Farm）宣布其自主研发的ALPK1激动剂DF-006免疫调节剂治疗慢性乙型肝炎患者的1b期研究DF-006-1001的数据将在2024年欧洲肝脏研究协会（EASL）大会上以“late breaking poster presentation（最新突破研究壁报）”形式展示。2024年EASL大会将于6月5日至8日在意大利米兰举行。药物牧场是一家致力于从靶点发现到“first-in-class”药物开发的生物科技公司，聚焦开拓乙肝、癌症、心脏和肾病以及ROSAH综合征等自身免疫性疾病的创新疗法。据悉，该公司的IDInVivo+平台结合遗传学和人工智能的突破性技术来发现新的治疗方法，可以在免疫系统健全的模式动物中直接挑选基因靶标。利用IDInVivo+平台，药物牧场已经发现多个全新先天免疫通路和靶点，目前正快速推进多个原创新药进入临床开发。DF-006是药物牧场开发的一种潜在“first-in-class”ALPK1激动剂免疫调节剂，可有效刺激肝脏中的局部先天免疫。DF-006目前已成功完成健康志愿者的单次和多次递增剂量评估，并在病毒学抑制的HBeAg阴性慢性乙型肝炎（CHB）患者中完成了多次递增剂量评估。“目前尚无有效治愈慢乙肝的方法。DF-006具有一种新的作用机制，能够刺激人体自身的免疫系统，帮助清除感染。作为一种每周给药一次的口服药物，DF-006有可能成为HBV联合治疗方案的首选免疫调节剂。”新西兰奥克兰大学医学教授、奥克兰医院首席肝病学家、移植医师兼新西兰肝移植科副主任爱德华·甘恩（Ed Gane）博士评价道。“DF-006已经显示出有效的临床前抗HBV反应，包括抑制环状DNA(cccDNA)和T细胞募集。这项1b期研究的数据为DF-006提供了临床支持，该药物可用于帮助治愈CHB患者。”药物牧场首席医学官Jeysen Yogaratnam博士说。本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床1期

2024-05-02

·BioSpace

Drug Farm Announces anti-HBV immunomodulator, DF-006 is Accepted as a Late-Breaking Presentation at the 2024 European Association for the Study of the Liver Conference

GUILFORD, Conn.--(BUSINESS WIRE)-- Drug Farm, a private biotechnology company utilizing genetics and artificial intelligence technologies to discover and develop innovative, immune-modulating therapies, today announced that the chronic hepatitis B patient data from their Phase 1b trial (ACTRN12621000592842) was accepted as a late breaking poster presentation at the 2024 European Association for the Study of the Liver (EASL) conference that will be held in Milan, Italy between 05 June 2024 to 08 June 2024. Poster #LB46 Title: A phase 1, double-blinded, randomized, placebo-controlled, multicenter global study evaluating the safety, tolerability, and antiviral activity of DF-006 in chronic hepatitis B, virologically-suppressed patients. Date: 05 June 2024 Time: 8.30 am – 5.00 pm CET DF-006 is a first-in-class, orally administered ALPK1 agonist immunomodulator that potently stimulates local, innate immunity in the liver1. DF-006 has successfully completed single and multiple ascending dose (MAD) evaluation in healthy volunteers, and MAD evaluation in virologically suppressed HBeAg negative chronic hepatitis B (CHB) patients. “There remains no effective cure for CHB. DF-006 has a novel mechanism of action that is capable of stimulating the body’s own immune system to help clear the infection. As an oral drug administered once weekly, DF-006 has the potential to be the immunomodulator of choice in combination HBV cure regimens”, said Dr. Ed Gane, Professor of Medicine at the University of Auckland, New Zealand and Chief Hepatologist, Transplant Physician, and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital. “DF-006 has demonstrated potent antiviral responses in preclinical studies, including inhibition of cccDNA and recruitment of T-cells. The data from this trial study now provides clinical support for a drug with a novel mechanism of action that could be used to help cure CHB patients”, said Drug Farm’s Chief Medical Officer, Dr. Jeysen Yogaratnam. About Drug Farm. Drug Farm is a private biotechnology Company developing innovative treatments targeting innate immunity for hepatitis B, cancer, and autoimmune diseases. Drug Farm's unique IDInVivo platform combines breakthrough technologies in genetics and AI to discover new treatments. IDInVivo technology allows the direct assessment of gene targets in living animals with intact immune systems. Using the IDInVivo platform, Drug Farm has identified novel innate immunity pathways and targets and is now rapidly advancing multiple first-in-class drug candidates into clinical development. For more information please visit: Reference: Xu C, et al. Hepatology. 2023 Jan 1;77(1):275-289. doi: 10.1002/hep.32614. Epub 2022 Sep 17. View source version on businesswire.com: Contacts United States: Henri Lichenstein, Ph.D. Chief Executive Officer Email: hlichens@drug-farm.com China: Tony Xu, Ph.D. Co-founder and Chief Operating Officer Email: tony.xu@drugfarminc.com Source: Drug Farm View this news release online at:

临床1期临床结果免疫疗法

100 项与 DF-006 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
慢性乙型肝炎	临床1期	澳大利亚	浙江药苑生物科技有限公司	2023-09-13
肝细胞癌	临床1期	-	上海药苑生物科技有限公司初创企业	-