Delving into the Latest Updates on Linxis B V with Synapse

Overview

Tags

Neoplasms

Respiratory Diseases

Skin and Musculoskeletal Diseases

Antibody drug conjugate (ADC)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	2

Top 5 Drug Type	Count

Antibody drug conjugate (ADC)	2

Top 5 Target	Count

HER2 x Tubulin	1
MAGEA1(Melanoma-associated antigen 1)	1

Author: van Dongen, Guus A. M. S. ; Schooten, Erik ; Noordman, Yvet E. ; Cali, Sagel ; van Dasselaar, Rychon D. J. ; Verheij, Joanne ; van de Graaf, Stan F. J. ; Eibergen, Arthur C. ; Nijmeijer, Bart A. ; Merkul, Eugen ; Muns, Joey A. ; Oliveira, Sabrina ; Sijbrandi, Niels J. ; Adamzek, Kevin ; Takkenberg, R. Bart ; Pronk, Sebas D. ; van Bergen en Henegouwen, Paul M. P.

Hepatic fibrosis develops as a response to chronic liver injury, resulting in the formation of fibrous scars.This process is initiated and driven by collagen-producing activated myofibroblasts which reportedly express high levels of platelet derived growth factor receptor-β (PDGFRβ).We therefore regard PDGFRβ as an anchor for diagnosis and therapy.The Fibrobody SP02SP26-ABD is a biparatopic VHH-construct targeting PDGFRβ.Here, we explore its potential as a theranostic vector for liver fibrosis.Specificity, cross-species binding, and cellular uptake of SP02SP26-ABD was assessed using human, mouse and rat PDGFRβ ectodomains and PDGFRβ-expressing cells.Cellular uptake by PDGFRβ-expressing cells was also evaluated by equipping the Fibrobody with auristatinF and reading out in vitro cytotoxicity.The validity of PDGFRβ as a marker for active fibrosis was confirmed in human liver samples and 3 mouse models of liver fibrosis (DDC, CCl4, CDA-HFD) through immunohistochem. and RT-PCR.After radiolabeling of DFO*-SP02SP26-ABD with 89Zr, its in vivo targeting ability was assessed in healthy mice and mice with liver fibrosis by PET-CT imaging, ex vivo biodistribution and autoradiog.SP02SP26-ABD shows similar nanomolar affinity for human, mouse and rat PDGFRβ.Cellular uptake and hence subnanomolar cytotoxic potency of auristatinF-conjugated SP02SP26-ABD was observed in PDGFRβ-expressing cell lines.Immunohistochem. of mouse and human fibrotic livers confirmed co-localization of PDGFRβ with markers of active fibrosis.In all three liver fibrosis models, PET-CT imaging and biodistribution anal. of [89Zr]Zr-SP02SP26-ABD revealed increased PDGFRβ-specific uptake in fibrotic livers.In the DDC model, liver uptake was 12.15 ± 0.45, 15.07 ± 0.90, 20.23 ± 1.34, and 20.93 ± 4.35%ID/g after 1,2,3 and 4 wk of fibrogenesis, resp., compared to 7.56 ± 0.85%ID/g in healthy mice.Autoradiog. revealed preferential uptake in the fibrotic (PDGFRβ-expressing) periportal areas.The anti-PDGFRβ Fibrobody SP02SP26-ABD shows selective and high-degree targeting of activated myofibroblasts in liver fibrosis, and qualifies as a vector for diagnostic and therapeutic purposes.

100 Deals associated with Linxis B V

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100 Translational Medicine associated with Linxis B V

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Pipeline

Pipeline Snapshot as of 10 Jan 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

Preclinical

2

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