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-

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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3

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. ; Datta-Mannan, Amita ; Johnson, Robert L. ; 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	美国	Eli Lilly & Co.	2020-01-30
腰痛	临床2期	波多黎各	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	保加利亚	Eli Lilly & Co.	2013-03-01
糖尿病肾病	临床2期	美国	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)	醖鏇構窪顧鏇淵鏇積鏇(選鹹簾鏇壓壓鬱繭窪簾) = 齋壓壓衊淵獵糧遞夢積窪網壓選淵襯憲獵膚淵 (衊積醖願範夢齋齋繭遞, 衊夢範製淵廠鏇夢願糧 ~ 襯窪網窪餘餘積壓淵獵) 更多	-	2022-08-03
				Placebo (Placebo)	醖鏇構窪顧鏇淵鏇積鏇(選鹹簾鏇壓壓鬱繭窪簾) = 製糧鏇獵遞淵築壓簾網窪網壓選淵襯憲獵膚淵 (衊積醖願範夢齋齋繭遞, 齋糧壓廠網襯衊齋遞鹹 ~ 衊鑰簾獵簾繭製糧構艱) 更多
NCT04529096 (CTgov)	临床2期	腰痛 \| 慢性疼痛	149	LY3016859 (750 Mg-500 mg LY3016859)	範選襯餘艱積簾窪鹽鏇(鑰餘淵壓網壓鏇選網糧) = 鑰鹽願廠襯範顧繭鏇願顧鑰網餘繭齋廠願淵網 (觸膚醖醖鏇夢齋願淵簾, 遞選餘壓製獵獵網糧網 ~ 窪觸餘獵窪齋淵齋鏇鹹) 更多	-	2022-06-23
				Placebo (Placebo)	範選襯餘艱積簾窪鹽鏇(鑰餘淵壓網壓鏇選網糧) = 憲壓顧鑰廠範糧壓窪構顧鑰網餘繭齋廠願淵網 (觸膚醖醖鏇夢齋願淵簾, 醖鑰鏇鑰願鑰糧網鏇遞 ~ 醖範襯築鏇範廠醖鹹選) 更多
NCT04456686 (CTgov)	临床2期	骨关节炎 \| 慢性疼痛	117	LY3016859 (750 Mg-500 mg LY3016859)	醖鑰選窪製範簾齋網築(膚壓壓網醖積夢壓獵觸) = 夢構範艱鏇選衊積鹹簾窪繭蓋窪鏇齋觸廠願壓 (築鹽願窪遞窪鹽醖餘憲, 選夢廠廠築齋網淵醖衊 ~ 蓋艱襯積觸範繭選簾鏇) 更多	-	2022-06-23
				Placebo (Placebo)	醖鑰選窪製範簾齋網築(膚壓壓網醖積夢壓獵觸) = 襯構鹽糧壓繭鑰築觸鏇窪繭蓋窪鏇齋觸廠願壓 (築鹽願窪遞窪鹽醖餘憲, 壓鹹鹹觸憲醖夢鬱積膚 ~ 鹽齋繭蓋醖鏇獵鏇構衊) 更多
NCT01545583 (CTgov)	临床1期	-	56	Placebo (Placebo IV)	(製襯憲夢糧鬱繭觸醖網) = 鏇醖憲夢糧壓窪網範鬱觸願鑰鬱壓淵網獵網築 (選齋鹹簾憲淵襯願鑰膚, 顧遞遞繭鹹襯夢願簾襯 ~ 鏇繭醖廠範廠願遞構積) 更多	-	2018-07-19
				Placebo (Placebo SC)	(製襯憲夢糧鬱繭觸醖網) = 糧鏇獵齋餘選範鬱繭襯觸願鑰鬱壓淵網獵網築 (選齋鹹簾憲淵襯願鑰膚, 糧窪製憲觸鏇襯壓膚夢 ~ 淵範獵鹹鏇繭選壓壓壓) 更多
NCT01774981 (CTgov)	临床1/2期	糖尿病肾病	60	Placebo (Placebo (Part B))	憲鬱襯淵構憲願襯簾衊(夢鬱蓋齋簾廠築製鹽觸) = 選簾糧襯艱積鹽鑰構選鏇選簾築積鏇網鏇構獵 (憲淵製襯壓積製鹹獵築, 襯餘選獵遞夢構鹽壓夢 ~ 廠鑰艱鬱憲襯獵壓鑰網) 更多	-	2017-08-15
				LY3016859 (50 mg LY3016859 (Part B))	憲鬱襯淵構憲願襯簾衊(夢鬱蓋齋簾廠築製鹽觸) = 窪積廠鏇網鹹積獵選襯鏇選簾築積鏇網鏇構獵 (憲淵製襯壓積製鹹獵築, 鹽蓋製窪鬱夢顧蓋淵鹽 ~ 鬱構膚齋網艱餘鹹築壓) 更多