TGF-alpha/epiregulin monoclonal antibody(Eli Lilly)(TGF-alpha/epiregulin monoclonal antibody(Eli Lilly)) - 药物靶点：EREG x TGF-α_在研适应症：慢性疼痛，糖尿病周围神经性疼痛，腰痛_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

EPIREG/TGFa MAB、Fepixnebart

+ [2]

靶点

EREG x TGF-α

作用方式

抑制剂

作用机制

EREG抑制剂(表皮调节素抑制剂)、TGF-α抑制剂(转化生长因子α抑制剂)

治疗领域

免疫系统疾病神经系统疾病内分泌与代谢疾病+ [1]

在研适应症

慢性疼痛糖尿病周围神经性疼痛腰痛+ [1]

非在研适应症

糖尿病肾病

原研机构

Eli Lilly & Co.

在研机构

Eli Lilly & Co.

非在研机构-

权益机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 126428H

来源: *****

Sequence Code 126431L

来源: *****

关联

6

项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的临床试验

NCT04529096

/ Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Chronic Low Back Pain

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of chronic low back pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-08-25

申办/合作机构

Eli Lilly & Co.

NCT04476108

/ Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Diabetic Peripheral Neuropathic Pain

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-07-15

申办/合作机构

Eli Lilly & Co.

NCT04456686

/ Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Osteoarthritis

This study is being done to test the safety and efficacy of LY3016859 for the treatment of osteoarthritis pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-07-01

申办/合作机构

Eli Lilly & Co.

100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的临床结果

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100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的转化医学

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100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的专利（医药）

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4

项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的文献（医药）

2018-09-01·Clinical Pharmacology in Drug Development4区 · 医学

Evaluation of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy After Single and Multiple Dosings of LY3016859 in Healthy Subjects and Patients With Diabetic Nephropathy

4区 · 医学

Article

作者: Eli, Michelle ; Raddad, Eyas ; Deeg, Mark A. ; Flynt, Amy ; Sloan‐Lancaster, Joanne ; Tumlin, James

AbstractTwo phase 1 studies (TGAA and TGAB) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of LY3016859 (LY), a monoclonal antibody that binds epiregulin and transforming growth factor α (TGF‐α), administered intravenously or subcutaneously. In TGAA, 56 healthy subjects received a single dose of LY (0.1–750 mg intravenously, 50 mg subcutaneously) or placebo. In TGAB part A, 15 patients with diabetic nephropathy (DN) received 2 doses of LY (10–750 mg intravenously) or placebo, and in TGAB part B, 45 patients with DN received 5 doses of LY (50–750 mg intravenously) or placebo. Pharmacokinetics, pharmacodynamics, anti‐LY antibodies, and change in proteinuria and albuminuria were evaluated. Single and multiple doses of LY administered 3 weeks apart were well tolerated. Pharmacokinetics were nonlinear in healthy subjects and patients with DN, indicating target‐mediated drug disposition. Epiregulin level increased in both studies, and TGF‐α levels increased in the TGAB study, consistent with target engagement; however, LY treatment did not significantly reduce proteinuria or albuminuria in patients with DN. There was no obvious effect of LY on the disease‐related biomarkers monocyte chemoattractant protein‐1, synaptopodin, or transferrin. Although LY administration resulted in a high frequency of anti‐LY antibodies, pharmacokinetics, target engagement, and efficacy were not impacted.

2016-11-01·Protein Science4区 · 生物学

Structural basis of selectivity and neutralizing activity of a TGFα/epiregulin specific antibody

4区 · 生物学

Article

作者: Boyles, Jeffrey S. ; Druzina, Zhanna ; Witcher, Derrick R. ; Atwell, Shane ; Heuer, Josef G.

AbstractRecent studies have implicated a role of the epidermal growth factor receptor (EGFR) pathway in kidney disease. Skin toxicity associated with therapeutics which completely block the EGFR pathway precludes their use in chronic dosing. Therefore, we developed antibodies which specifically neutralize the EGFR ligands TGFα (transforming growth factor‐alpha) and epiregulin but not EGF (epidermal growth factor), amphiregulin, betacellulin, HB‐EGF (heparin‐binding epidermal growth factor), or epigen. The epitope of one such neutralizing antibody, LY3016859, was characterized in detail to elucidate the structural basis for ligand specificity. Here we report a crystal structure of the LY3016859 Fab fragment in complex with soluble human TGFα. Our data demonstrate a conformational epitope located primarily within the C‐terminal subdomain of the ligand. In addition, point mutagenesis experiments were used to highlight specific amino acids which are critical for both antigen binding and neutralization, most notably Ala41, Glu44, and His45. These results illustrate the structural basis for the ligand specificity/selectivity of LY3016859 and could also provide insight into further engineering to alter specificity and/or affinity of LY3016859.

2014-05-01·The Journal of Pharmacology and Experimental Therapeutics3区 · 医学

Generation and Activity of a Humanized Monoclonal Antibody That Selectively Neutralizes the Epidermal Growth Factor Receptor Ligands Transforming Growth Factor-α and Epiregulin

3区 · 医学

Article

作者: Breyer, Matthew D. ; Yang, Derek D. ; Harlan, Shannon M. ; Johnson, Robert L. ; Datta-Mannan, Amita ; Ellis, Bernice ; Petrovan, Ramona J. ; Heuer, Josef G. ; Chu, Shaoyou ; Conner, Elaine M. ; Witcher, Derrick R. ; Beidler, Catherine B. ; Stauber, Anja ; Boyles, Jeffrey S.

At least seven distinct epidermal growth factor (EGF) ligands bind to and activate the EGF receptor (EGFR). This activation plays an important role in the embryo and in the maintenance of adult tissues. Importantly, pharmacologic EGFR inhibition also plays a critical role in the pathophysiology of diverse disease states, especially cancer. The roles of specific EGFR ligands are poorly defined in these disease states. Accumulating evidence suggests a role for transforming growth factor α (TGFα) in skin, lung, and kidney disease. To explore the role of Tgfa, we generated a monoclonal antibody (mAb41) that binds to and neutralizes human Tgfa with high affinity (KD = 36.5 pM). The antibody also binds human epiregulin (Ereg) (KD = 346.6 pM) and inhibits ligand induced myofibroblast cell proliferation (IC50 values of 0.52 and 1.12 nM for human Tgfa and Ereg, respectively). In vivo, a single administration of the antibody to pregnant mice (30 mg/kg s.c. at day 14 after plug) or weekly administration to neonate mice (20 mg/kg s.c. for 4 weeks) phenocopy Tgfa knockout mice with curly whiskers, stunted growth, and expansion of the hypertrophic zone of growth plate cartilage. Humanization of this monoclonal antibody to a human IgG4 antibody (LY3016859) enables clinical development. Importantly, administration of the humanized antibody to cynomolgus monkeys is absent of the skin toxicity observed with current EGFR inhibitors used clinically and no other pathologies were noted, indicating that neutralization of Tgfa could provide a relatively safe profile as it advances in clinical development.

100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 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
慢性疼痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
慢性疼痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
糖尿病周围神经性疼痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
糖尿病周围神经性疼痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
腰痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
腰痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
膝关节炎	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
膝关节炎	临床2期	美国	Eli Lilly & Co.	2020-01-30
糖尿病肾病	临床2期	美国	Eli Lilly & Co.	2013-03-01
糖尿病肾病	临床2期	保加利亚	Eli Lilly & Co.	2013-03-01

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临床结果

适应症

分期

评价

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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


NCT04476108 (CTgov)	临床2期	慢性疼痛 \| 糖尿病周围神经性疼痛	125	LY3016859 (750 Mg-500 mg LY3016859)	積醖鹽蓋鹽鹽憲憲齋鹽(獵鏇鑰齋憲餘選積蓋鏇) = 鬱窪憲齋襯襯壓窪築獵糧蓋製範範範鏇簾繭廠 (壓醖襯積繭遞憲壓築夢, 憲築鬱醖築蓋選築構網 ~ 遞遞願艱鑰壓壓願範範) 更多	-	2022-08-03
				Placebo (Placebo)	積醖鹽蓋鹽鹽憲憲齋鹽(獵鏇鑰齋憲餘選積蓋鏇) = 築壓獵衊糧膚範顧廠齋糧蓋製範範範鏇簾繭廠 (壓醖襯積繭遞憲壓築夢, 積膚壓廠繭鑰衊蓋鏇鹹 ~ 鹽壓夢繭繭觸範簾構壓) 更多
NCT04456686 (CTgov)	临床2期	骨关节炎 \| 慢性疼痛	117	LY3016859 (750 Mg-500 mg LY3016859)	糧簾鏇壓鹽艱獵夢鏇糧(網鑰觸蓋積顧網艱遞膚) = 遞壓獵膚繭壓淵鹹鏇製餘膚衊選範繭構構鹹築 (獵餘繭顧齋積願艱窪壓, 壓觸簾鹽餘廠獵膚憲網 ~ 網簾齋鹹構獵簾鹹廠積) 更多	-	2022-06-23
				Placebo (Placebo)	糧簾鏇壓鹽艱獵夢鏇糧(網鑰觸蓋積顧網艱遞膚) = 艱遞範餘壓繭淵壓製衊餘膚衊選範繭構構鹹築 (獵餘繭顧齋積願艱窪壓, 艱衊鹹顧觸簾艱鹹窪遞 ~ 觸鬱廠積襯製憲繭獵廠) 更多
NCT04529096 (CTgov)	临床2期	腰痛 \| 慢性疼痛	149	LY3016859 (750 Mg-500 mg LY3016859)	壓繭鬱鑰廠築襯鏇壓淵(餘壓網鹽築遞製窪獵築) = 糧衊鹽製衊夢艱觸繭簾鹽衊積鹹糧積獵淵襯鏇 (範製築淵衊製鏇繭餘壓, 醖鑰簾簾鑰壓壓衊遞構 ~ 鹹鏇廠繭網壓繭觸衊艱) 更多	-	2022-06-23
				Placebo (Placebo)	壓繭鬱鑰廠築襯鏇壓淵(餘壓網鹽築遞製窪獵築) = 鑰製築艱蓋壓繭繭餘夢鹽衊積鹹糧積獵淵襯鏇 (範製築淵衊製鏇繭餘壓, 構醖鏇鹹獵顧衊選製膚 ~ 範築壓範築廠製觸鑰淵) 更多
NCT01545583 (CTgov)	临床1期	-	56	Placebo (Placebo IV)	(壓願襯齋夢築餘餘製齋) = 壓淵範鑰簾窪鏇積醖糧鏇鬱壓齋糧繭遞製遞鏇 (膚遞製鬱範顧遞鏇鑰顧, 構鑰構膚蓋範糧膚構廠 ~ 積鹹淵願鬱顧構蓋衊獵) 更多	-	2018-07-19
				Placebo (Placebo SC)	(壓願襯齋夢築餘餘製齋) = 繭窪醖簾願鬱繭鹹觸廠鏇鬱壓齋糧繭遞製遞鏇 (膚遞製鬱範顧遞鏇鑰顧, 壓艱蓋範糧蓋窪淵獵觸 ~ 醖鏇襯襯製鬱壓膚齋願) 更多
NCT01774981 (CTgov)	临床1/2期	糖尿病肾病	60	Placebo (Placebo (Part B))	繭鑰壓憲製鹽醖齋顧簾(願窪範齋夢齋範觸鹹壓) = 廠觸顧憲齋醖築鑰淵夢蓋製餘襯鑰鬱選構齋廠 (艱範鏇網遞鏇膚憲願衊, 醖糧願遞膚鹽鹹製顧積 ~ 觸壓鏇選遞顧鑰鑰構廠) 更多	-	2017-08-15
				LY3016859 (50 mg LY3016859 (Part B))	繭鑰壓憲製鹽醖齋顧簾(願窪範齋夢齋範觸鹹壓) = 製淵蓋壓築鹽壓鏇夢糧蓋製餘襯鑰鬱選構齋廠 (艱範鏇網遞鏇膚憲願衊, 餘壓遞膚觸遞繭醖鬱醖 ~ 壓衊築網膚選繭遞鏇憲) 更多