Delving into the Latest Updates on Zucero Therapeutics Pty Ltd. with Synapse

概览

排名前五的药物类型	数量

小分子化药	1

关联

2

项与 Zucero Therapeutics Pty Ltd. 相关的药物

ZUC002

靶点-

作用机制-

在研机构

Zucero Therapeutics Pty Ltd.

原研机构

Zucero Therapeutics Pty Ltd.

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

PG-545

靶点

HPSE

作用机制

乙酰肝素酶抑制剂 [+1]

在研机构-

原研机构

TBG Diagnostics Ltd.

在研适应症-

非在研适应症

晚期恶性实体瘤 [+7]

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

2

项与 Zucero Therapeutics Pty Ltd. 相关的临床试验

NCT02042781 / Completed临床1期

An Open-label, Multi-centre Phase I Study of the Safety and Tolerability of IV Infused PG545 in Patients With Advanced Solid Tumours

This Phase Ia study aims to establish the maximum tolerated dose of once-weekly IV infused PG545 and to evaluate its safety in subjects with advanced solid tumours. In addition, the study will explore whether PG545 exposure results in changes to chemicals produced by the body that are associated with cancer growth and spread.

开始日期2014-01-01

申办/合作机构

Zucero Therapeutics Pty Ltd.

NCT01252095 / Terminated临床1期

An Open-label, Single Centre Phase I Study of the Safety and Tolerability of PG545 in Patients With Advanced Solid Tumours

This first-in-human study aims to establish the maximum tolerated dose of PG545 and to evaluate its safety in subjects with advanced solid tumours. In addition the study will explore whether PG545 exposure results in changes to chemicals produced by the body that are associated with cancer growth and spread.

开始日期2011-01-01

申办/合作机构

Zucero Therapeutics Pty Ltd.

[+2]

100 项与 Zucero Therapeutics Pty Ltd. 相关的临床结果

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0 项与 Zucero Therapeutics Pty Ltd. 相关的专利（医药）

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2

项与 Zucero Therapeutics Pty Ltd. 相关的文献（医药）

2017-08-01·Molecular Cancer Therapeutics2区 · 医学

Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth

2区 · 医学

Article

作者: Spyrou, Argyris ; Forsberg-Nilsson, Karin ; Vlodavsky, Israel ; Haseeb, Lulu ; Kundu, Soumi ; Dredge, Keith ; Olofsson, Tommie ; Barash, Uri ; Hammond, Edward ; Yu, Di

AbstractCurative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM. Here, we report that the levels of HPSE in pediatric brain tumors are higher than in healthy brain tissue and that treatment of pediatric brain tumor cells with HPSE stimulated their growth. In addition, the latent, 65 kDa form of HPSE (that requires intracellular enzymatic processing for activation) enhanced cell viability and rapidly activated the ERK and AKT signaling pathways, before enzymatically active HPSE was detected. The HPSE inhibitor PG545 efficiently killed pediatric brain tumor cells, but not normal human astrocytes, and this compound also reduced tumor cell invasion in vitro and potently reduced the size of flank tumors in vivo. Our findings indicate that HPSE in malignant brain tumors affects both the tumor cells themselves and their ECM. In conclusion, HPSE plays a substantial role in childhood brain tumors, by contributing to tumor aggressiveness and thereby represents a potential therapeutic target. Mol Cancer Ther; 16(8); 1705–16. ©2017 AACR.

2017-05-20·Journal of Clinical Oncology

An open-label, multi-center phase I study of the safety and tolerability of the novel immunomodulatory agent PG545 in subjects with advanced solid tumors.

作者: Bampton, Darryn ; Lin, Liwen ; Brennan, Todd ; Yang, Yiping ; Hammond, Edward ; Dredge, Keith ; Brown, Michael Paul ; Millward, Michael ; Lickliter, Jason D.

3083 Background: PG545 (pixatimod, pINN) is a novel immunomodulatory agent which stimulates dendritic cells (DC) via TLR9/IL-12 pathway to activate natural killer (NK) cells. It also inhibits tumour-associated macrophages in cancer models. We report on safety, PK, PD, and antitumor activity of PG545 monotherapy. Methods: In this dose escalation (3+3 design) study, eligible pts (ECOG≤1) with advanced solid malignancies who failed standard therapies received PG545 once weekly as a 1-hour i.v. infusion until disease progression or discontinuation due to intolerability. The primary objective was determination of the maximum tolerated dose (MTD). Secondary objectives evaluated safety, antitumor activity based on RECIST (1.1) criteria, PK and PD (plasmacytoid DC & NKp46+NK cells from PBMC, and plasma cytokines/chemokines). Results: The study recruited 23 subjects across four cohorts (25, 50, 100 & 150 mg). Three dose limiting toxicities (DLTs) - hypertension (2), epistaxis (1) - occurred in the 150 mg cohort, which was identified as a non-tolerated dose level. No DLTs occurred in the 100 mg cohort, which was identified as the MTD. Six SAEs were reported to be possibly or likely related to PG545 treatment. No RECIST 1.1 objective responses were reported; best response was prolonged stable disease up to 24 weeks (mCRC), with disease control rate in evaluable subjects of 38% (6/16) at eight weeks. Exposure (AUC0-last) was proportional up to 100mg and mean half-life was 144 hours. At 50 and 100mg dose levels, two subjects in each cohort exhibited up to 4-fold increased numbers of NKp46+NK cells, IFN-α-producing pDCs, and increases (up to 25-fold) in plasma IFN-γ, TNF-α, IP-10 and MCP-1. Conclusions: PG545 is well tolerated up to 100 mg once-weekly via i.v. infusion. Human exposure data at 50mg and 100mg reach exposures consistent with those required for preclinical efficacy. Preliminary PD data support the proposed mechanism of action, which represents a promising approach to improve the efficacy of existing therapies. These data, and the absence of toxicities associated with chemo- or immunotherapies, support the development of PG545 in combination clinical trials. Clinical trial information: NCT02042781.

100 项与 Zucero Therapeutics Pty Ltd. 相关的药物交易

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100 项与 Zucero Therapeutics Pty Ltd. 相关的转化医学

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