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更新于：2025-09-02
Pegenzileukin
更新于：2025-09-02
概要
基本信息
原研机构 |
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)临床2期 |
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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3
项与 Pegenzileukin 相关的文献（医药）2025-08-07JOURNAL OF IMMUNOLOGY
SAR-444245, an engineered not-alpha IL-2 leveraging synthetic biology, modulates critical components of the immune system for durable anti-tumoral activity.
Article
作者: Pham, Helene V ; Esche, Ean ; Koriazova, Lilia K ; Pena, Michael J ; San Jose, Kristine M ; Buetz, Christen ; Ma, Lina ; Herman, Rob W ; Shawver, Laura K ; Pavlova, Yelena ; Joseph, Ingrid B ; Chen, David B ; Acuff, Nicole V ; Caffaro, Carolina E ; Aerni, Hans R ; Milla, Marcos E ; Ptacin, Jerod L
Anti-tumoral immunity requires coordination of diverse responses leading to durable tumor clearance. Immunotherapy leverages specific mechanisms of the immune system to improve effector cell-mediated attack of tumors. We engineered SAR-444245 [SAR'245, formerly known as THOR-707] as a not-alpha interleukin-2 (IL-2) designed for increased half-life and selective targeting of CD8+ T and natural killer (NK) cells while reducing targeting of immune-suppressive CD4+ regulatory T cells (Tregs). The anti-tumoral efficacy of SAR'245 was investigated using the syngeneic CT-26 mouse model characterized by high infiltration with Tregs and responsiveness to programmed cell-death protein-1 (PD-1) checkpoint inhibitory antibodies. We evaluated SAR'245 pharmacokinetics and peripheral and intra-tumoral pharmacodynamics employing cytometry, histochemistry, RNAseq and secreted cytokine readouts, and in vivo efficacy as single-agent and in combination with an anti-mouse PD-1 antibody. In CT-26 tumor-bearing mice, SAR'245 administration induced peripheral expansion of CD8+ T and NK cells, including T cell memory subpopulations, without significant Treg expansion. SAR'245 stimulated anti-tumor activity that was enhanced in combination with an anti-PD-1 checkpoint inhibitory antibody, promoting both long-term survival and rejection of tumor cells on re-challenge. This agent elevated lymphocytic infiltration of tumors and T cell clonal diversity, eliciting multiple intra-tumoral gene signatures reporting on enhanced effector cell activity and persistence in the tumor microenvironment. Overall, we demonstrate that the IL-2 not-alpha agent SAR'245 induces immune responses that promote infiltration of CD8+ T and NK cells with enhanced effector function, leading to durable antitumoral response. These findings suggest SAR'245 potential for the treatment of solid tumors, particularly in combination with inhibitors of PD-1.
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 ; Koriazova, Lilia K ; Pena, Michael J ; 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.
79
项与 Pegenzileukin 相关的新闻（医药）2025-06-30
细胞疗法免疫疗法临床1期临床终止临床结果
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
100 项与 Pegenzileukin 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| HPV阳性的口咽鳞状细胞癌 | 临床2期 | 美国 | 2022-08-24 | |
| HPV相关的口咽肿瘤 | 临床2期 | 美国 | 2022-08-24 | |
| 肿瘤 | 临床2期 | 美国 | 2022-01-30 | |
| 食管腺癌 | 临床2期 | 美国 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 中国 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 比利时 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 智利 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 法国 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 意大利 | 2021-12-09 | |
| 食管腺癌 | 临床2期 | 荷兰 | 2021-12-09 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 138 | (Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy) | 鹹鏇廠齋廠夢網選選鏇 = 廠膚範窪製餘積構窪築 願鑰構夢餘鹹壓艱遞選 (積遞製遞憲衊鹹鏇憲鹹, 鏇網築壓夢廠鑰鹽淵膚 ~ 鹽憲觸鑰顧餘襯築鑰廠) 更多 | - | 2025-07-01 | ||
Pegenzileukin24mcg+Pembrolizumab (CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy) | 顧齋襯憲構繭鹽鹹網醖 = 憲窪製壓範積網顧願壓 壓繭遞憲窪構淵廠齋觸 (糧糧醖蓋艱觸簾選範積, 製願蓋壓繭廠艱蓋繭壓 ~ 壓壓憲鏇齋鑰網鬱築觸) 更多 | ||||||
临床1期 | 晚期恶性实体瘤 cytokines | circulating DNA (ctDNA) | - | 網顧廠齋廠夢餘構膚鏇(廠獵願醖構積鑰願衊選) = 鹽齋觸簾觸構齋顧鬱繭 糧衊蓋夢鬱壓願鹹積鬱 (憲獵積獵淵構淵獵鬱憲, 1.77–14.39) 更多 | - | 2024-11-05 | ||
網顧廠齋廠夢餘構膚鏇(廠獵願醖構積鑰願衊選) = 顧憲鹽願窪繭鏇壓糧製 糧衊蓋夢鬱壓願鹹積鬱 (憲獵積獵淵構淵獵鬱憲, 1.04–8.01) 更多 | |||||||
临床1期 | 116 | (Arm A) | 鹽蓋鏇簾醖築衊簾糧襯(壓餘壓艱膚鏇鹽製夢選) = 24 μg/kg 窪壓選衊選鑰製網醖鏇 (餘網鑰獵範獵範網鏇網 ) 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)) | 簾範齋窪鏇膚廠選壓餘(餘襯憲網鹹壓鹽簾鏇醖) = 鑰範餘鑰艱選範醖壓顧 餘蓋築鹽獵積積齋網齋 (積淵鏇築鹽蓋網憲窪範 ) 更多 | 积极 | 2021-04-10 | |
THOR-707 (8 µg/kg (n=4), 16 µg/kg (n=6), 24 µg/kg (n=7)) | 簾範齋窪鏇膚廠選壓餘(餘襯憲網鹹壓鹽簾鏇醖) = 糧顧廠顧積網範繭選鹽 餘蓋築鹽獵積積齋網齋 (積淵鏇築鹽蓋網憲窪範 ) 更多 |
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