Delving into the Latest Updates on PrecisemAb Biotech Co., Ltd with Synapse

Overview

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Neoplasms

Other Diseases

Congenital Disorders

Antibody drug conjugate (ADC)

Monoclonal antibody

Antibody

Disease domain score

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Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	4
Immune System Diseases	1
Nervous System Diseases	1

Top 5 Drug Type	Count

Antibody drug conjugate (ADC)	3
Antibody	1
Probody	1
Monoclonal antibody	1

Top 5 Target	Count

EGFR(Epidermal growth factor receptor erbB1)	1
CanAg(Tumor-associated carbohydrate antigen CanAg)	1
IL-1β(Interleukin-1 beta)	1

Author: Lin, Wen-Wei ; Shen, Ying-Rou ; Ho, Kai-Wen ; Chang, Tong-Husan ; Liao, Tzu-Yi ; Cheng, Tian-Lu ; Hong, Shih-Ting ; Hsieh, Yi-Hsuan ; Wu, Hsuan-Hui ; Lee, Yu-Chi ; Lu, Yun-Chi ; Lee, Wen-Han ; Chang, Chia-Chun ; Chen, Yen-Ying ; Liu, Liang-Yirn ; Chen, Ching-Kuei ; Yang, Mei-Chun ; Cheng, Yi-An ; Huang, Bo-Cheng

Lewis Y carbohydrate antigen is overexpressed in various epithelial cancers, making it a potential therapeutic target. However, anti-Lewis Y antibodies have faced challenges due to gastrointestinal toxicity from Lewis Y antigen expression in normal tissues. To mitigate the toxicity, we engineered L-HKM4, a protease-activated anti-Lewis Y antibody, by modifying the N-terminal of HKM4 with an IgG1 hinge domain and a matrix metalloproteinase (MMP)-cleavable linker. This design ensures selective activation in the MMP2/9-rich gastric and colon tumor microenvironment, minimizing off-tumor effects. The results demonstrated that L-HKM4 binding to AGS gastric cancer cells decreased 104.6-fold compared to HKM4, accompanied by a 15.82-fold reduction in antibody-dependent cell-mediated cytotoxicity (ADCC) and no activity in complement-dependent cytotoxicity (CDC), all of binding and cytotoxicity were restored upon MMP2 activation. In mice, L-HKM4 showed minimal gastric tissue binding, confirming reduced on-target toxicity in vivo. In an AGS xenograft model, L-HKM4 achieved tumor-specific activation and inhibited tumor growth by 82 % (P < 0.001) compared to saline control. In conclusion, L-HKM4 enables tumor-specific activation while minimizing gastric toxicity, preserving strong tumor inhibition. This innovative approach overcomes key limitations of anti-Lewis Y therapies, making L-HKM4 a promising and safer treatment for gastrointestinal cancers.

01 May 2025·International Journal of Biological Macromolecules

Development of a tumor-region-selective activation monoclonal antibody targeting the 4-1BB receptor for enhanced therapeutic efficacy and safety

Article

Author: Chen, Michael ; Cheng, Yi-An ; Chen, Chiao-Yun ; Chuang, Chih-Hung ; Ho, Kai-Wen ; Huang, Bo-Cheng ; Lin, Wen-Wei ; Chuang, Kuo-Hsiang ; Liu, En-Shuo ; Chen, Fang-Ming ; Liao, Tzu-Yi ; Hong, Shih-Ting ; Liu, Yen-Ling ; Cheng, Tian-Lu ; Wu, Bing-Tsung

4-1BB is a co-stimulatory immune checkpoint receptor that triggers CD8⁺ T cell activation, leading to robust anti-tumor responses. Although antibodies targeting 4-1BB show promise in preclinical studies, systemic 4-1BB over-activation can cause severe hepatotoxicity, limiting their clinical use. In this study, we developed Pro-Urelumab, an engineered version of the clinical anti-4-1BB antibody (Urelumab), utilizing an autologous hinge as a spatial hindrance-based antibody lock, linked the antibody and antibody lock with a matrix metalloproteinase-2/9 (MMP-2/9) substrate. This design selectively reactivates Pro-Urelumab within the tumor microenvironment, reducing systemic toxicity. Our results demonstrated that Pro-Urelumab exhibited a 389-fold reduction in binding ability toward the 4-1BB receptor compared to Urelumab, effectively preventing pro-inflammatory cytokine secretion from T cells. After MMP-2/9 cleavage, its agonist activity was fully restored. In a human T-cell-transfer mouse model, Pro-Urelumab avoided the 4-1BB antigen sink effect without causing organ damage. Mice treated with Pro-Urelumab exhibited 100 % survival over 14 days, while all Urelumab-treated mice succumbed to treatment-related toxicity. Additionally, Pro-Urelumab achieved 77 % tumor growth inhibition (TGI), compared to 45 % with Urelumab, and significantly increased T cell activation within the tumor. This study underscores the potential of tumor-selective 4-1BB activation for enhancing both the efficacy and safety of immuno-oncology therapies.

100 Deals associated with PrecisemAb Biotech Co., Ltd

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100 Translational Medicine associated with PrecisemAb Biotech Co., Ltd

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Pipeline

Pipeline Snapshot as of 16 May 2025

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

Discovery

1

5

Preclinical

Other

5

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

PSM101-ADC	Solid tumor More	Preclinical
PSM-101	Head and Neck Neoplasms More	Preclinical
Lock-EGFR-ADC ( EGFR )	Neoplasms More	Preclinical
TBD(PrecisemAb Biotech)	Transient Bullous Dermolysis of the Newborn More	Preclinical
Lock-IL-1β ( IL-1β )	Multiple Sclerosis More	Preclinical