PRS-080(PRS-080) - 药物靶点：Hepc_专利_临床

概要

基本信息

药物类型

重组蛋白

别名

靶点

Hepc

作用机制

Hepc抑制剂(铁调素抑制剂)

治疗领域

内分泌与代谢疾病血液及淋巴系统疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

贫血缺铁性贫血慢性肾衰竭贫血

原研机构

Pieris Pharmaceuticals, Inc.

在研机构-

非在研机构

Pieris Pharmaceuticals GmbH

Pieris Pharmaceuticals, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

5

项与 PRS-080 相关的临床试验

NCT03325621 / Completed临床1/2期

Phase 2a Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Repeated Administrations Over 4 Weeks of the Hepcidin Antagonist PRS-080#022-DP in Anemic Chronic Kidney Disease Patients Undergoing Hemodialysis

Anticalin® proteins are engineered human proteins that are able to bind specific target molecules. The Anticalin PRS-080#022-DP to be investigated in this study is directed against hepcidin and is intended for the treatment of anemia of chronic disease. This pilot Phase 2a study shall investigate the safety, pharmacokinetics and pharmacodynamics of repeated administrations of PRS-080#022-DP in anemic stage 5 chronic kidney disease (CKD) patients undergoing hemodialysis.

开始日期2017-09-30

申办/合作机构

Pieris Pharmaceuticals GmbH

[+1]

EUCTR2016-004472-21-DE / Not yet recruiting临床2期

Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis

开始日期2017-08-31

申办/合作机构

Pieris Pharmaceuticals GmbH

EUCTR2016-004472-21-CZ / Not yet recruiting临床2期

Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis

开始日期2017-08-31

申办/合作机构

Pieris Pharmaceuticals GmbH

100 项与 PRS-080 相关的临床结果

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100 项与 PRS-080 相关的转化医学

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100 项与 PRS-080 相关的专利（医药）

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2

项与 PRS-080 相关的文献（医药）

2018-06-01·BioDrugs

Anticalin® Proteins as Therapeutic Agents in Human Diseases

Review

作者: Rothe, Christine ; Skerra, Arne

Anticalin proteins are an emerging class of clinical-stage biopharmaceuticals with high potential as an alternative to antibodies. Anticalin molecules are generated by combinatorial design from natural lipocalins, which are abundant plasma proteins in humans, and reveal a simple, compact fold dominated by a central β-barrel, supporting four structurally variable loops that form a binding site. Reshaping of this loop region results in Anticalin proteins that can recognize and tightly bind a wide range of medically relevant targets, from small molecules to peptides and proteins, as validated by X-ray structural analysis. Their robust format allows for modification in several ways, both as fusion proteins and by chemical conjugation, for example, to tune plasma half-life. Antagonistic Anticalin therapeutics have been developed for systemic administration (e.g., PRS-080: anti-hepcidin) or pulmonary delivery (e.g. PRS-060/AZD1402: anti-interleukin [IL]-4-Rα). Moreover, Anticalin proteins allow molecular formatting as bi- and even multispecific fusion proteins, especially in combination with antibodies that provide a second specificity. For example, PRS-343, which has recently entered clinical-stage development, combines an agonistic Anticalin targeting the costimulatory receptor 4-1BB with an antibody directed against the cancer antigen human epidermal growth factor receptor 2 (HER2), thus offering a novel treatment option in immuno-oncology.

2018-04-01·British Journal of Pharmacology2区 · 医学

Sustained plasma hepcidin suppression and iron elevation by Anticalin‐derived hepcidin antagonist in cynomolgus monkey

2区 · 医学

Article

作者: Rattenstetter, Barbara ; Gille, Hendrik ; Meibohm, Bernd ; Christian, Hans Jürgen ; Swinkels, Dorine W ; Laarakkers, Coby M ; Olwill, Shane A ; Trentmann, Stefan ; Katzmann, Galina ; Andersen, Nicole ; Hohlbaum, Andreas M ; Allersdorfer, Andrea ; Kolodziejczyk, Maria ; van Swelm, Rachel P L ; Audoly, Laurent P

Background and PurposeAnaemia of chronic disease (ACD) has been linked to iron‐restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte‐derived peptide that controls systemic iron homeostasis. Here, we report the engineering of the human lipocalin‐derived, small protein‐based anticalin PRS‐080 hepcidin antagonist with high affinity and selectivity.Experimental ApproachAnticalin‐ and hepcidin‐specific pharmacokinetic (PK)/pharmacodynamic modelling (PD) was used to design and select the suitable drug candidate based on t1/2 extension and duration of hepcidin suppression. The development of a novel free hepcidin assay enabled accurate analysis of bioactive hepcidin suppression and elucidation of the observed plasma iron levels after PRS‐080‐PEG30 administration in vivo.Key ResultsPRS‐080 had a hepcidin‐binding affinity of 0.07 nM and, after coupling to 30 kD PEG (PRS‐080‐PEG30), a t1/2 of 43 h in cynomolgus monkeys. Dose‐dependent iron mobilization and hepcidin suppression were observed after a single i.v. dose of PRS‐080‐PEG30 in cynomolgus monkeys. Importantly, in these animals, suppression of free hepcidin and subsequent plasma iron elevation were sustained during repeated s.c. dosing. After repeated dosing and followed by a treatment‐free interval, all iron parameters returned to pre‐dose values.Conclusions and ImplicationsIn conclusion, we developed a dose‐dependent and safe approach for the direct suppression of hepcidin, resulting in prolonged iron mobilization to alleviate iron‐restricted erythropoiesis that can address the root cause of ACD. PRS‐080‐PEG30 is currently in early clinical development.

100 项与 PRS-080 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性肾衰竭贫血	临床2期	捷克	Pieris Pharmaceuticals GmbH	2017-09-30
慢性肾衰竭贫血	临床2期	德国	Pieris Pharmaceuticals GmbH	2017-09-30
贫血	临床2期	德国	Pieris Pharmaceuticals GmbH	2016-06-06
缺铁性贫血	临床2期	捷克	Pieris Pharmaceuticals, Inc.	-
缺铁性贫血	临床2期	德国	Pieris Pharmaceuticals, Inc.	-

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临床结果

适应症

分期

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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


NCT02754167 (Pubmed \| J Biol Chem) 人工标引	临床1期	慢性肾病	72	PRS 080 (1b：CKD undergoing hemodialysis)	(窪壓構簾憲蓋衊憲製獵) = 齋觸窪顧壓憲顧窪膚鏇艱鑰淵襯鏇願範鹹餘製 (醖製構遞窪鹽構顧顧網 ) 更多	积极	2019-03-27