Delving into the Latest Updates on Nanjing Hongyun Biotechnology Co., Ltd. with Synapse

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Respiratory Diseases

Neoplasms

Small molecule drug

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A glimpse into the focused therapeutic areas

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Disease Domain	Count

Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	2

Top 5 Target	Count

HPK1(Mitogen-activated protein kinase kinase kinase kinase 1)	1
EGFR C797S(Epidermal Growth Factor Receptor C797S)	1

[Translation] An open-label, dose-escalation and expansion phase I/IIa clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of H002 in patients with locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor mutation-positive

评估H002的安全性和耐受性，并确定最大耐受剂量（MTD）或最佳生物效应剂量（OBD）/II期推荐剂量（RP2D）。评估H002口服给药的药代动力学（PK）特征。评估H002治疗的初步抗肿瘤作用。

[Translation]

To evaluate the safety and tolerability of H002 and determine the maximum tolerated dose (MTD) or optimal biological effect dose (OBD)/recommended dose for Phase II (RP2D). To evaluate the pharmacokinetic (PK) characteristics of oral administration of H002. To evaluate the preliminary anti-tumor effect of H002 treatment.

Start Date12 Aug 2022

Sponsor / Collaborator

Nanjing Hongyun Biotechnology Co., Ltd.

100 Clinical Results associated with Nanjing Hongyun Biotechnology Co., Ltd.

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0 Patents (Medical) associated with Nanjing Hongyun Biotechnology Co., Ltd.

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2

Literatures (Medical) associated with Nanjing Hongyun Biotechnology Co., Ltd.

01 Oct 2022·International Journal of Biological Macromolecules

Atomic resolution Cryo-EM structure of human proteasome activator PA28γ

Article

Author: Shen, Chao-Hui ; Deng, Xian-Ming ; Chen, Dan-Dan ; Hao, Jia ; Yun, Cai-Hong

The PA28 family proteasome activators play important roles in regulating proteasome activities. Though the three paralogs (PA28α, PA28β, and PA28γ) are similar in terms of primary sequence, they show significant differences in expression pattern, cellular localization and most importantly, biological functions. While PA28αβ is responsible for promoting peptidase activity of proteasome to facilitate MHC-I antigen processing, but unable to promote protein degradation, PA28γ is well-known to not only promote peptidase activity but also proteolytic activity of proteasome. However, why this paralog has the unique function remains elusive. Previous structural studies have mainly focused on mammalian PA28α, PA28β and PA28αβ heptamers, while structural studies on mammalian PA28γ of atomic resolution are still absent to date. In the present work, we determined the Cryo-EM structure of the human PA28γ heptamer at atomic resolution, revealing interesting unique structural features that may hint our understanding the functional mechanisms of this proteasome activator.

15 Jun 2022·Cancer Research

Abstract 5461: H002: A wide spectrum, highly selective fourth-generation EGFR inhibitor overcoming resistance harboring C797S mutation in NSCLC

Author: Zhang, Jianming ; Li, Haibo ; Huang, Wei ; Yun, Caihong ; Li, Xiangyu ; Hao, Jia ; Chen, Zhiming ; Huang, Xin ; Yan, Xiaoe ; Zhu, Lin ; Deng, Xianming ; Jia, Yunchuan ; Li, Shan

AbstractBACKGROUND: Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major challenge in non-small cell lung cancer (NSCLC) treatment. EGFR activating mutations, such as exon 19 deletions (Del19) and L858R substitution, have been reported in 10-50% of patients with NSCLC. Although these patients respond well to early generations of TKIs, acquired resistance by mechanisms such as T790M mutation compromises their efficacy. Recently, the C797S mutation in combination with Del19 or L858R, and with T790M, has emerged as one of the most common mechanisms underlying on-target resistance to a third generation EGFR TKI, osimertinib. We are developing a fourth-generation EGFR inhibitor, H002, with a wide spectrum and high selectivity to address the growing unmet needs in NSCLC patients harboring C797S mutation.METHODS: H002’s selectivity was assessed by KINOMEscan against more than 400 human kinases. A panel of 44 kinases was further evaluated to enable early identification of off-target effect. In vitro and in vivo anti-tumor efficacy was determined in drug-resistant mutant cell lines, CDX and PDX models. Single mutants (Del or L858R), double mutants (Del/T790M or L858R/T790M) and triple mutants (Del/T790M/C797S or L858R/T790M/C797S) as well as wild type EGFR were assessed. Drug metabolism and pharmacokinetic (DMPK) properties were further assessed. H002’s safety profile was evaluated in rats and beagle dogs, and by hERG potassium channel assay. Acute toxicity, and repeated dose GLP toxicity studies were also conducted in IND-enabling studies.RESULTS: High kinase selectivity and very low off-target effects were demonstrated by kinome-wide profiling and safety screening. H002 was highly active against all forementioned single, double or triple EGFR mutants (IC50 < 5 nM), and highly selective against wild type EGFR. H002 also exhibited potent anti-tumor effects in a dose-dependent manner in various CDX and PDX models. Excellent PK properties were observed in rats and beagle dogs with bioavailability over 70%. H002 was shown to cross the blood-brain barrier post i.g. administration in rats. No adverse effects of respiratory, cardiovascular and central nervous system were observed in safety studies. Repeated-dose toxicity studies only showed EGFR-related adverse reactions, such as gastrointestinal and liver toxicity, with high safety margin over 10-folds.CONCLUSION: H002 has been demonstrated as a promising next generation EGFR inhibitor, with high selectivity, a wide spectrum and potent anti-tumor activity against various EGFR activating mutations, favorable DMPK and safety profiles. It will be further developed as a fourth-generation EGFR inhibitor to overcome drug resistance in NSCLC.Citation Format: Wei Huang, Lin Zhu, Xiaoe Yan, Xin Huang, Jia Hao, Shan Li, Xiangyu Li, Zhiming Chen, Yunchuan Jia, Haibo Li, Jianming Zhang, Xianming Deng, Caihong Yun. H002: A wide spectrum, highly selective fourth-generation EGFR inhibitor overcoming resistance harboring C797S mutation in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5461.

100 Deals associated with Nanjing Hongyun Biotechnology Co., Ltd.

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100 Translational Medicine associated with Nanjing Hongyun Biotechnology Co., Ltd.

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Pipeline

Pipeline Snapshot as of 16 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Phase 2 Clinical

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