预约演示
更新于：2025-04-28
Pegenzileukin
更新于：2025-04-28
概要
基本信息
原研机构 |
在研机构 |
最高研发阶段临床1/2期 |
首次获批日期- |
最高研发阶段(中国)终止 |
特殊审评- |
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结构/序列
Sequence Code 611938424
来源: *****
关联
9
项与 Pegenzileukin 相关的临床试验NCT05535023
Phase 2 Study of Neoadjuvant SAR444245 Plus Cemiplimab in HPV Related Oropharynx
CTR20220689
一项评估SAR444245（THOR-707）联合其他抗癌疗法治疗晚期和转移性胃肠癌受试者的临床获益的II 期、非随机、开放标签、多队列、多中心研究（Pegasus Gastrointestinal 203）
NCT05104567
A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Advanced and Metastatic Gastrointestinal Cancer
100 项与 Pegenzileukin 相关的临床结果
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100 项与 Pegenzileukin 相关的转化医学
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100 项与 Pegenzileukin 相关的专利（医药）
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2
项与 Pegenzileukin 相关的文献（医药）2024-10-01Cancer research communications
A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates
Article
作者: Shawver, Laura K. ; Milla, Marcos E. ; San Jose, Kristine M. ; Acuff, Nicole V. ; Leveque, Joseph A. ; Pena, Michael J. ; Caffaro, Carolina E. ; Buetz, Christen ; Herman, Rob W. ; Ma, Lina ; Pham, Helene V. ; Byers, Anthony M. ; Ismaili, Taylor K. ; Koriazova, Lilia K. ; Joseph, Ingrid B. ; Chen, David B. ; Sassoon, Ingrid ; Carrio, Roberto ; Cucchetti, Margot ; Ptacin, Jerod L. ; Mooney, Jill M. ; Pavlova, Yelena ; Aerni, Hans R.
Abstract:
We have created a precisely pegylated IL-2 [SAR-444245 (SAR’245) or pegenzileukin, previously THOR-707] designed for proliferation of target CD8+ T and NK cells for anticancer activity, with minimal expansion of anti-target regulatory CD4+ T cells (Treg) that counter their action, or eosinophils that trigger vascular leak syndrome (VLS). We performed in vivo studies in nonhuman primates (NHP) to monitor the safety of SAR’245, pharmacokinetic profile, and pharmacodynamic parameters including expansion of peripheral CD8+ T and NK cells, and effects on Tregs and eosinophils. Studies included multiple ascending dosing and repeat dosing with different regimens (QW, Q2W, Q3W and Q4W). We also conducted ex vivo studies using human primary cells to further evaluate SAR’245 stimulation of target cells alone and in combination with programmed cell-death 1 (PD-1) checkpoint inhibitors. The pharmacokinetic profile of SAR’245 in NHP demonstrated dose-proportional exposure that was comparable with redosing. It elicited expansion of peripheral CD8+ T and NK cells that was comparable with each dose and with multiple dosing regimens. Once-weekly dosing showed no significant adverse effects, including no hallmark signs of VLS at dosing levels up to 1 mg/kg. Ex vivo, SAR’245 enhanced T-cell receptor responses alone and in combination with PD-1 inhibitors without inducing cytokines associated with cytokine release syndrome or VLS. Results support the clinical development of SAR’245 as a drug candidate for the treatment of solid tumors, alone or in combination with PD-1 inhibitory agents.
Significance::
SAR-444245 (SAR’245, pegenzileukin) is an extended half-life IL-2 that targets effector CD8+ T and NK cells, with little effect on regulatory T cells. We show that in the nonhuman primate model that closely approximates human immune function and response to IL-2, SAR’245 selectively activates CD8+ T and NK effectors without significant serious side effects (vascular leak syndrome or cytokine release syndrome), suggesting its potential for the treatment of solid tumors in humans.
Nature communications1区 · 综合性期刊
An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism
1区 · 综合性期刊
ArticleOA
作者: Caffaro, Carolina E ; Pena, Michael J ; Koriazova, Lilia K ; Shawver, Laura K ; Ma, Lina ; Herman, Rob W ; Joseph, Ingrid B ; Pavlova, Yelena ; Chen, David B ; San Jose Gall, Kristine M ; Milla, Marcos E ; Aerni, Hans R ; Acuff, Nicole V ; Ptacin, Jerod L
Abstract:
The implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties. One variant, termed THOR-707, selectively engages the IL-2 receptor beta/gamma complex without engagement of the IL-2 receptor alpha. In mice, administration of THOR-707 results in large-scale activation and amplification of CD8+T cells and NK cells, without Treg expansion characteristic of IL-2. In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating CD8+T and NK cells, and leads to a dose-dependent reduction of tumor growth. These results support further characterization of the immune modulatory, anti-tumor properties of THOR-707 and represent a fundamental advance in the application of synthetic biology to medicine, leveraging engineered semi-synthetic organisms as cellular factories to facilitate discovery and production of differentiated classes of chemically modified biologics.
78
项与 Pegenzileukin 相关的新闻（医药）2025-04-16
·靶点圈
细胞疗法临床结果临床研究免疫疗法
2025-02-20
·医药速览
抗体药物偶联物
2025-02-15
引进/卖出临床3期并购免疫疗法抗体药物偶联物
100 项与 Pegenzileukin 相关的药物交易
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研发状态
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 116 | (Arm A) | 獵築鏇襯窪廠鏇壓齋遞(襯遞襯範餘簾構遞淵範) = 24 μg/kg 觸襯壓繭鹽鹽鑰鹹鬱蓋 (蓋淵選鹹築蓋選衊遞遞 ) 更多 | 积极 | 2022-09-10 | ||
(Arm B) | |||||||
临床1/2期 | 实体瘤 二线 | 28 | THOR-707 (8 µg/kg (n=4)) | 糧蓋積憲製艱鬱鏇獵鑰(糧膚膚構鏇鹹鏇蓋醖蓋) = 鹹餘醖鏇獵範餘遞範襯 夢築願壓蓋膚廠廠壓淵 (繭繭蓋範築鏇夢廠繭顧 ) 更多 | 积极 | 2021-04-10 | |
THOR-707 (8 µg/kg (n=4), 16 µg/kg (n=6), 24 µg/kg (n=7)) | 糧蓋積憲製艱鬱鏇獵鑰(糧膚膚構鏇鹹鏇蓋醖蓋) = 蓋選鹽繭積糧淵鹽獵構 夢築願壓蓋膚廠廠壓淵 (繭繭蓋範築鏇夢廠繭顧 ) 更多 |
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