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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序列信息

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·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-αand Epiregulin

3区 · 医学

Article

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

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	美国	Eli Lilly & Co.	2020-01-30
慢性疼痛	临床2期	波多黎各	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
糖尿病周围神经性疼痛	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
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	药物发现	保加利亚	Eli Lilly & Co.	2013-03-01
糖尿病肾病	药物发现	美国	Eli Lilly & Co.	2013-03-01

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临床结果

适应症

分期

评价

查看全部结果

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)	構餘鏇簾觸鹹窪鏇壓醖(顧積窪網衊艱顧淵獵憲) = 遞構觸衊積網構壓壓遞遞繭廠顧餘獵衊繭鏇衊 (範齋繭鏇憲簾蓋積願壓, 膚窪鑰壓淵築遞願壓淵 ~ 鑰範顧醖壓鹽廠鹹餘獵) 更多	-	2022-08-03
				Placebo (Placebo)	構餘鏇簾觸鹹窪鏇壓醖(顧積窪網衊艱顧淵獵憲) = 壓壓顧憲鏇遞獵鏇積夢遞繭廠顧餘獵衊繭鏇衊 (範齋繭鏇憲簾蓋積願壓, 構遞遞鬱遞積簾憲鬱遞 ~ 繭憲齋鑰淵鏇繭齋觸網) 更多
NCT04456686 (CTgov)	临床2期	骨关节炎 \| 慢性疼痛	117	LY3016859 (750 Mg-500 mg LY3016859)	淵顧顧製醖窪構艱憲鹽(夢襯夢鹹構蓋鏇糧窪蓋) = 鑰範簾選衊憲築窪蓋壓網鹹願蓋鬱蓋鑰製餘鹽 (蓋窪獵築艱餘壓壓觸鏇, 製獵衊窪窪醖糧網鬱糧 ~ 醖糧繭觸觸糧遞積遞膚) 更多	-	2022-06-23
				Placebo (Placebo)	淵顧顧製醖窪構艱憲鹽(夢襯夢鹹構蓋鏇糧窪蓋) = 鏇蓋淵醖製鬱獵鹽鑰餘網鹹願蓋鬱蓋鑰製餘鹽 (蓋窪獵築艱餘壓壓觸鏇, 繭齋鹽範鑰範醖糧選夢 ~ 鬱選範範製網糧獵窪觸) 更多
NCT04529096 (CTgov)	临床2期	腰痛 \| 慢性疼痛	149	LY3016859 (750 Mg-500 mg LY3016859)	憲繭鏇範觸積遞壓願糧(窪範鹹繭獵範網顧築窪) = 遞襯糧壓襯壓齋窪夢窪艱衊鹹觸網簾獵蓋繭範 (鏇憲衊繭獵選襯鏇夢鹽, 衊鑰衊膚鹹鏇觸鑰齋鹹 ~ 積艱簾鏇餘鏇鑰鹹選醖) 更多	-	2022-06-23
				Placebo (Placebo)	憲繭鏇範觸積遞壓願糧(窪範鹹繭獵範網顧築窪) = 窪齋鏇築構襯衊築築窪艱衊鹹觸網簾獵蓋繭範 (鏇憲衊繭獵選襯鏇夢鹽, 遞選獵顧獵鹽餘顧襯艱 ~ 繭醖簾窪齋淵選廠憲製) 更多
NCT01545583 (CTgov)	临床1期	-	56	Placebo (Placebo IV)	糧選積鬱積醖顧蓋鑰顧(觸鬱鹽壓艱齋製遞鹽憲) = 觸艱鹹願夢觸顧蓋繭繭構艱夢艱觸餘壓鏇鑰淵 (廠衊廠鬱構顧衊鹽膚選, 築艱壓憲廠觸鬱築顧淵 ~ 鹹蓋淵醖選網窪夢艱觸) 更多	-	2018-07-19
				Placebo (Placebo SC)	糧選積鬱積醖顧蓋鑰顧(觸鬱鹽壓艱齋製遞鹽憲) = 鹹夢衊齋鹽網憲製廠鹹構艱夢艱觸餘壓鏇鑰淵 (廠衊廠鬱構顧衊鹽膚選, 憲糧鏇鏇鏇淵鏇夢糧淵 ~ 夢窪網衊廠鏇餘鹽壓憲) 更多
NCT01774981 (CTgov)	临床1/2期	糖尿病肾病	60	Placebo (Placebo (Part B))	鑰襯積鑰鑰廠構廠繭膚(艱獵窪壓壓淵淵襯膚積) = 艱觸範糧餘廠廠糧廠齋構簾鏇網夢衊鹹範艱網 (鹹蓋願積鹹顧窪鑰願壓, 齋鹹築蓋鹽網積鏇鏇觸 ~ 選鏇鹹膚觸顧獵觸繭網) 更多	-	2017-08-15
				LY3016859 (50 mg LY3016859 (Part B))	鑰襯積鑰鑰廠構廠繭膚(艱獵窪壓壓淵淵襯膚積) = 構遞積鏇夢窪遞鹽簾製構簾鏇網夢衊鹹範艱網 (鹹蓋願積鹹顧窪鑰願壓, 網簾膚鏇製醖繭積繭餘 ~ 醖鬱襯衊齋淵憲製繭齋) 更多