PPMX-T003(PPMX-T003) - 药物靶点：TfR1_在研适应症：真性红细胞增多症，大颗粒淋巴细胞白血病_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

靶点

TfR1

作用机制

TfR1拮抗剂(转铁蛋白受体1拮抗剂)

治疗领域

肿瘤血液及淋巴系统疾病其他疾病+ [1]

在研适应症

真性红细胞增多症大颗粒淋巴细胞白血病

非在研适应症-

原研机构

Perseus Proteomics, Inc.

在研机构

Tokai University

Perseus Proteomics, Inc.

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 PPMX-T003 相关的临床试验

JPRN-jRCT2061230008 / Recruiting临床1/2期IIT

Multicentre, open-label, dose-escalation phase I/II study to evaluate the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive NK cell leukaemia (ANKL) (physician-initiated clinical trial).

开始日期2023-09-21

申办/合作机构-

NCT05863234 / Recruiting临床1/2期IIT

Multicenter, Open-label, Dose-escalation Phase I/II Study to Evaluate the Tolerability, Safety, Efficacy and Pharmacokinetics of Repeated Continuous Intravenous PPMX-T003 in Patients With Aggressive NK Cell Leukaemia (ANKL) (Physician-initiated Clinical Trial)

This is Phase I/II Dose-Escalation Study to evaluate the tolerability, safety, efficacy and pharmacokinetics of PPMX-T003 in aggressive NK-cell leukemia.

开始日期2023-04-20

申办/合作机构

Hiroshima University

NCT05074550 / Recruiting临床1期

Phase I, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of A Single Intravenous PPMX-T003 in Polycythemia Vera

This is PhaseI Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of PPMX-T003 in Polycythemia Vera

开始日期2022-08-24

申办/合作机构

Perseus Proteomics, Inc.

100 项与 PPMX-T003 相关的临床结果

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100 项与 PPMX-T003 相关的转化医学

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100 项与 PPMX-T003 相关的专利（医药）

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3

项与 PPMX-T003 相关的文献（医药）

2024-08-01·Leukemia

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia

Article

作者: Nakamura, Naoya ; Hirao, Atsushi ; Nakagawa, So ; Matsuura, Tadashi ; Onizuka, Makoto ; Carreras, Joaquim ; Hasegawa, Ami ; Ando, Kiyoshi ; Yamauchi, Takuji ; Kameda, Kazuaki ; Watanabe, Natsumi ; Yanagiya, Ryo ; Handa, Hiroshi ; Miyatake, Yuji ; Mashima, Tetsuo ; Ueno, Masaya ; Kanamori, Akane ; Kotani, Ai ; Kamakura, Takeshi ; Maeda, Takahiro ; Ishizawa, Kenichi ; Okabe, Sachiko ; Ishii, Keisuke ; Nakayama, Shunya ; Shimizu, Takanobu

AbstractAggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition. However, the microenvironmental factors that regulate the iron dependency of ANKL cells remain unclear. In this study, we first revealed that the anti-neoplastic effect of PPMX-T003 was characterized by DNA double-strand breaks in a DNA replication-dependent manner, similar to conventional cytotoxic agents. We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut.

2023-07-27·Blood

The hepatic niche leads to aggressive natural killer cell leukemia proliferation through the transferrin-transferrin receptor 1 axis.

Article

作者: Ishida, Fumihiro ; Takahashi, Naoto ; Ishihara, Rei ; Nakazawa, Hideyuki ; Carreras, Joaquim ; Harigae, Hideo ; Nakamura, Naoya ; Miyatake, Yuji ; Fukuhara, Noriko ; Iida, Shinsuke ; Yanagiya, Ryo ; Fujioka, Yuki ; Ando, Kiyoshi ; Murakami, Yuki ; Nakagawa, So ; Imadome, Ken-Ichi ; Higuchi, Hiroshi ; Kanda, Yoshinobu ; Matsuura, Tadashi ; Tagawa, Hiroyuki ; Murayama, Hiromichi ; Ishida, Takashi ; Iwabuchi, Sadahiro ; Hashimoto, Shinichi ; Ito, Asahi ; Wada, Hidenori ; Ishizawa, Kenichi ; Kameda, Kazuaki ; Kotani, Ai

Aggressive natural killer cell leukemia (ANKL) is a rare lymphoid neoplasm frequently associated with Epstein-Barr virus, with a disastrously poor prognosis. Owing to the lack of samples from patients with ANKL and relevant murine models, comprehensive investigation of its pathogenesis including the tumor microenvironment (TME) has been hindered. Here we established 3 xenograft mice derived from patients with ANKL (PDXs), which enabled extensive analysis of tumor cells and their TME. ANKL cells primarily engrafted and proliferated in the hepatic sinusoid. Hepatic ANKL cells were characterized by an enriched Myc-pathway and proliferated faster than those in other organs. Interactome analyses and in vivo CRISPR-Cas9 analyses revealed transferrin (Tf)-transferrin receptor 1 (TfR1) axis as a potential molecular interaction between the liver and ANKL. ANKL cells were rather vulnerable to iron deprivation. PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a noncanonical hematopoietic organ in adults, serves as a principal niche for ANKL and the inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.

2023-06-01·Clinical Pharmacology in Drug Development

Phase 1 Clinical Trial of PPMX‐T003, a Novel Human Monoclonal Antibody Specific for Transferrin Receptor 1, to Evaluate Its Safety, Pharmacokinetics, and Pharmacodynamics

Article

作者: Kirisako, Hiromi ; Komatsu, Norio ; Nomura, Fumiko ; Ohira, Yuta ; Yamamoto, Yukiya ; Yokokawa, Takuya ; Araki, Marito ; Matsuura, Tadashi ; Kumagai, Yuji ; Masubuchi, Nami ; Kyoya, Akiko ; Akiyoshi, Hiroko ; Ogama, Yoichiro

AbstractThis study aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of PPMX‐T003, a novel human monoclonal antibody for transferrin receptor 1 (TFR1), in healthy individuals. Forty participants were enrolled and randomized to PPMX‐T003 dose groups (n = 6/group) and the placebo group (n = 10). The safety and pharmacokinetics profiles were assessed according to the sequential, ascending single‐dose intravenous infusions of PPMX‐T003 from 0.008 mg/kg to 0.25 mg/kg. Adverse events (AEs) after PPMX‐T003 administration occurred in 16 of 30 participants. Any severe AE and AE incidence were not reported, but they tended to increase depending on the dose. Laboratory tests, vital signs, and standard 12‐lead electrocardiogram showed no clinically relevant changes. Five participants experienced an infusion‐related reaction but recovered on days 5–10. Regarding pharmacokinetics, PPMX‐T003 has a nonlinear elimination pattern. PPMX‐T003 in the 0.25 mg/kg group showed apparent (>50%) decreased serum levels of reticulocytes from day 3 and sustained moderate (<10%) fall of hematocrit and hemoglobin counts from day 7. In conclusion, the antibody‐mediated blockade of TFR1 elicited the expected fall in blood cell levels and showed an acceptable safety profile, supporting the continuing development of PPMX‐T003 as a new candidate for polycythemia vera treatment.

100 项与 PPMX-T003 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
真性红细胞增多症	临床1期	日本	Perseus Proteomics, Inc.	2022-08-24
大颗粒淋巴细胞白血病	临床前	日本	Perseus Proteomics, Inc.	-
大颗粒淋巴细胞白血病	临床前	日本	Tokai University	-

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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


PPMX-T003 (AACR2017)	N/A	血液肿瘤	-	PPMX-T003	糧餘齋壓積窪齋積顧鏇(鏇蓋築襯遞廠襯窪顧淵) = 廠築鑰鏇積艱衊遞選糧網壓襯鏇窪鬱簾網齋蓋 (壓簾夢鬱範齋製窪膚醖 )	积极	2017-07-01