SIM-323(SIM-323) - 药物靶点：CD28 x CTLA4 x IL-2Rβγ_在研适应症：晚期恶性实体瘤，膀胱癌，结直肠癌_专利_临床

概要

基本信息

药物类型

Fc融合蛋白

别名

CD80-IgG4 Fc-IL2v、GI 101、GI-101

+ [2]

靶点

CD28 x CTLA4 x IL-2Rβγ

作用方式

抑制剂、激动剂

作用机制

CD28抑制剂(T细胞特异性表面糖蛋白CD28抑制剂)、CTLA4抑制剂(细胞毒性T淋巴细胞相关抗原4抑制剂)、IL-2Rβγ激动剂(白细胞介素-2受体βγ亚基复合物激动剂)

治疗领域

肿瘤感染消化系统疾病+ [4]

在研适应症

晚期恶性实体瘤膀胱癌结直肠癌+ [11]

非在研适应症-

原研机构

在研机构

非在研机构

权益机构

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)无进展

特殊审评孤儿药 (美国)

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结构/序列

Sequence Code 5063

靶点: *****

Sequence Code 6077linker

Sequence Code 315647156

Sequence Code 524284409linker

Sequence Code 524284410

Sequence Code 524284411

Sequence Code 524284413Fusion protein

关联

2

项与 SIM-323 相关的临床试验

KCT0009580

/ Not yet recruiting临床2期IIT

Phase 2a, open-label, multi-center study of GI-101A or GI-102 (CD80-IgG4 FC-IL2v) in patients with relapsed/refractory diffuse large B-cell lymphoma following anti-CD19 chimeric antigen receptor T-cell therapy (CARNATION)

开始日期2024-07-31

申办/合作机构

Asan Medical Center

NCT04977453

/ Recruiting临床1/2期

A Phase 1/2, Open-label, Dose-escalation, and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101 as a Single Agent and in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Patients With Advanced or Metastatic Solid Tumors (Keynote B59)

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.

开始日期2021-08-02

申办/合作机构

GI Innovation, Inc.

[+1]

100 项与 SIM-323 相关的临床结果

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100 项与 SIM-323 相关的转化医学

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100 项与 SIM-323 相关的专利（医药）

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13

项与 SIM-323 相关的文献（医药）

2012-12-01·Journal of translational medicine2区 · 医学

Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells

2区 · 医学

ArticleOA

作者: Aladar A Szalay ; Huiqiang Wang ; Boris R Minev ; Nanhai G Chen

Abstract:

Background:

Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy.

Methods:

Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44+CD24+ESA+cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models.

Results:

We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44+CD24+ESA+cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44+CD24-ESA+cells.

Conclusions:

Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.

2011-05-01·AMERICAN JOURNAL OF PATHOLOGY

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Article

作者: Price, Janet E. ; Marchetti, Dario ; Lee, Ju-Seog ; Guo, Lixia ; Zhang, Fahao ; Langley, Robert R. ; Fidler, Isaiah J. ; Fan, Dominic

An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic potential is highly desirable. Here, we demonstrate that plating GI-101A human breast cancer cells on hard (0.9%) agar selects for the subpopulation of metastasis-initiating cells. The agar-selected cells, designated GI-AGR, were homogeneous for CD44(+) and CD133(+) and five times more invasive than the parental GI-101A cells. Moreover, mice injected with GI-AGR cells had significantly more experimental brain metastases and shorter overall survival than did mice injected with GI-101A cells. Comparative gene expression analysis revealed that GI-AGR cells were markedly distinct from the parental cells but shared an overlapping pattern of gene expression with the GI-101A subline GI-BRN, which was generated by repeated in vivo recycling of GI-101A cells in an experimental brain metastasis model. Data mining on 216 genes shared between GI-AGR and GI-BRN breast cancer cells suggested that the molecular phenotype of these cells is consistent with that of cancer stem cells and the aggressive basal subtype of breast cancer. Collectively, these results demonstrate that analysis of cell growth in a hard agar assay is a powerful tool for selecting metastasis-initiating cells in a heterogeneous population of breast cancer cells, and that such selected cells have properties similar to those of tumor cells that are selected based on their potential to form metastases in mice.

2011-01-01·Cancer gene therapy2区 · 医学

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

2区 · 医学

Article

作者: J M von Hof ; L F Tietze ; M Hess ; J B Sturm ; I Gentschev ; N Chen ; C M Seubert ; B Krewer ; A A Szalay ; U Donat ; J Stritzker

Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed enzyme prodrug therapy. Here, the lacZ-carrying vaccinia virus (VACV) strain GLV-1h68 was used in combination with a β-galactosidase-activatable prodrug derived from a seco-analog of the natural antibiotic duocarmycin SA. Tumor cell infection with the VACV strain GLV-1h68 led to production of β-galactosidase, essential for the conversion of the prodrug to the toxic compound. Furthermore, drug-dependent cell kill and induction of the intrinsic apoptosis pathway in tumor cells was also observed on combination therapy using the prodrug and the GLV-1h68 strain, despite the fact that VACV strains encode antiapoptotic proteins. Moreover, GI-101A breast cancer xenografts were effectively treated by the combination therapy. In conclusion, the combination of a β-galactosidase-activatable prodrug with a tumor-specific vaccinica virus strain encoding this enzyme, induced apoptosis in cultures of the human GI-101A breast cancer cells, in which a synergistic oncolytic effect was observed. Moreover, in vivo, additional prodrug treatment had beneficial effects on tumor regression in GLV-1h68-treated GI-101A-xenografted mice.

5

项与 SIM-323 相关的新闻（医药）

2025-01-22

·PRNewswire

GI Innovation-LaNova Medicines Signs MOU for GI-102 + ADC Pancreatic Cancer Combination Therapy

SEOUL, South Korea, Jan. 22, 2025 /PRNewswire/ -- GI Innovation (KQ:358570) announced that it signed a Memorandum of Understanding (MOU) with LaNova Medicines (LaNova) for the development of GI-102 and ADC pancreatic cancer combination therapy. This MOU was held on January 15th, local time, during JP Morgan Healthcare Conference (San Francisco, USA). Continue Reading From the left, Rhee Byung-geon, Chairman and CEO of GI Innovation, Dr. Crystal Quin, CEO of LaNova Medicines, and Jang Myoung-ho, CSO of GI Innovation. (Source: GI Innovation) The two companies have been conducting combination therapy study of the immuno-oncology drug GI-102 and ADC LM-302 targeting Claudin18.2 and recently observed excellent anticancer activity in a preclinical pancreatic cancer model. Both substances are in the clinical stage. GI-102 has completed phase 1 clinical trial in the US and Korea and can quickly enter phase 2. LM-302 is currently in phase 3 clinical trial for 3L and above gastric cancer in China. Pancreatic cancer has no approved immunotherapy, and the only approved treatment is a chemotherapy cocktail, but its treatment efficacy is low and its toxicity is high. Through this agreement, both companies will conduct clinical trial targeting patients with metastatic pancreatic cancer. Dr. Myoung Ho Jang, CSO said, "We are delighted to be conducting a combination study with LaNova, which is recognized by global pharma companies. LaNova's ADC, which directly destroys tumor cells to increase the response rate, and GI-102, which can enhance immune memory to increase overall survival, are expected to be a combination therapy that can change the pancreatic cancer treatment paradigm." "GI-102 exemplifies GI Innovation's robust R&D capabilities in immunotherapy. We are excited to explore its combination with LaNova's Claudin18.2 ADC, LM-302, which holds the potential to provide a novel therapeutic option for pancreatic cancer patients" Dr. Crystal Qin, LaNova CEO emphasized. About GI Inovation GI Innovation, a KOSDAQ-listed biotech, pioneers fusion protein drugs for cancer and allergies. Since 2017, it secured $230 million through funding rounds, IPO, and licensing deals for preclinical and clinical assets. Leveraging global partnerships for rapid development, the leading programs include immuno-oncology assets GI-101, subcutaneous form GI-102, and anti-allergy asset GI-301, metabolic immuno-oncology asset GI-108 alongside other innovative programs. SOURCE GI Innovation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期免疫疗法临床2期抗体药物偶联物上市批准

2024-10-25

·药研网

先声药业癌症新药CDH6 ADC申报临床

10月25日，CDE官网显示，先声药业旗下先祥医药申报的1类新药—注射用SIM0505的临床试验申请获得NMPA受理。据其官网，SIM0505为一款 CDH6 ADC，是先声药业申报的首款ADC新药，也是第2款国产CDH6 ADC。根据管线信息，先声药业SIM0686（FGFR2b-ADC）、SIM0323（CD80/IL-2双功能融合蛋白）等抗肿瘤管线也处于临床前阶段。 2024年8月22日，先声药业旗下抗肿瘤创新药公司先声再明宣布，其自主研发的抗肿瘤候选药物－DNA聚合酶θ（Polθ）小分子抑制剂SIM0508已获得国家药监局批准开展药物临床试验，拟用于治疗晚期实体瘤。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾 1 8月 | 高达22家药企裁员 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

抗体药物偶联物优先审批疫苗申请上市并购

2024-08-26

·Business Wire

GI Innovation Announces New Clinical Trial Collaboration and Supply Agreement to Evaluate GI-102 in Combination with KEYTRUDA® (pembrolizumab) in Patients with Immunotherapy-Resistant Liver Cancer, Melanoma, and Renal Cell Carcinoma

SEOUL, South Korea--( BUSINESS WIRE )--The South Korean biotech company GI Innovation announced today that it has signed a clinical trial collaboration and supply agreement with MSD (a tradename of Merck& Co., Inc., Rahway, NJ, USA) to evaluate the combination of GI-102 and MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in patients with immunotherapy-resistant liver cancer, melanoma, and renal cell carcinoma. This agreement marks GI Innovation’s second clinical trial collaboration with MSD, following a previous collaboration for GI-101A. The Phase 2 clinical trial including GI-102 in combination with KEYTRUDA will enroll patients with resistance or non-response to immuno-oncology treatments, leaving them with no further treatment options. GI Innovation is focused on three indications with significant market potential and potential likelihood of success: metastatic liver cancer, melanoma, and renal cell carcinoma. The company has already demonstrated strong anti-cancer efficacy with a 42.9% overall response rate (ORR) in a monotherapy trial of GI-102 in melanoma patients who failed to respond to standard-of-care treatment (3 partial responses out of 7 patients). Complete tumor regression was previously observed in 60% of mice treated with GI-102 monotherapy in a preclinical liver cancer model. Fourteen hospitals in South Korea and world-renowned sites in the U.S. have agreed to join the trial, including the Mayo Clinic (campuses in Rochester, Florida, and Arizona), Cleveland Clinic and Memorial Sloan Kettering Cancer Center. In South Korea, the trial will take place at leading hospitals including Samsung Medical Center, Asan Medical Center, Seoul National University Hospital, Severance Hospital of Yonsei University, and St. Vincent’s Hospital. "We are pleased to enter into another clinical trial collaboration and supply agreement with MSD, a world leader in immuno-oncology. We aim to maximize the therapeutic value of GI-102 by combining it with KEYTRUDA, MSD’s anti-PD-1 therapy”, said Dr Myung-Ho Jang, GI Innovation’s Chief Scientific Officer. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway NJ, USA.

临床2期免疫疗法

100 项与 SIM-323 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
晚期恶性实体瘤	临床2期	美国	GI Innovation, Inc.	2021-08-02
晚期恶性实体瘤	临床2期	韩国	GI Innovation, Inc.	2021-08-02
膀胱癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
膀胱癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02
结直肠癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
结直肠癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02
食管鳞状细胞癌	临床2期	美国	GI Innovation, Inc.	2021-08-02
食管鳞状细胞癌	临床2期	韩国	GI Innovation, Inc.	2021-08-02
黑色素瘤	临床2期	美国	GI Innovation, Inc.	2021-08-02
黑色素瘤	临床2期	韩国	GI Innovation, Inc.	2021-08-02

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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


NCT04977453 (Keynote-B59, SITC2023)	临床1/2期	晚期恶性实体瘤	25	GI-101 (CD80-IL2v) + Pembrolizumab	製繭網襯齋糧夢鹽蓋繭(鏇鑰繭襯顧膚範簾鹽廠) = 28%, 24% 築製簾簾築壓憲蓋願鬱 (膚淵獵構壓襯選遞鹽獵 ) 更多	积极	2023-11-02
NCT04977453 (GII-101-P101, ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	晚期恶性实体瘤	57	GI-101	糧簾繭夢鹽選鏇鬱範憲(構製繭製糧膚憲壓襯膚) = 築襯夢繭獵衊膚範餘淵築簾鬱襯憲廠選鹽選鑰 (鹽顧積鑰襯顧積糧鏇壓 ) 更多	积极	2023-10-23
				GI-101 (MSS CRC with liver metastasis)	願範構蓋製艱艱觸簾憲(積夢鏇糧鹽鹹顧願醖製) = 衊網鏇網繭窪壓簾夢淵範獵繭築糧艱願壓選築 (顧窪齋遞鏇繭窪製餘鑰 )
NCT04977453 (GII-101-P101, SITC 12022 \| SITC 22022) 人工标引	临床1/2期	转移性实体瘤	25	GI-101	鬱蓋顧艱積繭獵糧糧積(築觸窪遞鏇觸網蓋簾顧) = No dose-limiting toxicities up to 0.15 mg/kg were reported with planned dose level of 0.002~0.6 mg/kg. 夢選夢醖鹹顧獵積願壓 (淵觸觸觸衊顧鹽膚憲齋 )	积极	2022-11-01
				pembrolizumab+GI-101