Publications

A successful search for new, efficient, and silverfree manufacturing processes for key platinum(II) intermediates applied in antibody–drug conjugate (ADC) production

​Merkul et al. Green Chemistry. 2020.

In this paper, we describe the multigram scale manufacturing of the crucial drug-Lx linker complexes as direct precursors for our Lx ADCs. The publication proudly underlines our environmentally and economically benign approach to ADC manufacturing.

First platinum(II)-based metal-organic linker technology (Lx®) for a plug-and-play development of antibody-drug conjugates (ADCs)

​Merkul et al. Expert Opinion on Drug Delivery. 2019.

In this peer-reviewed paper, we summarize all advantages that our platinum-based Lx® linker technology holds for the development and manufacturing of antibody-drug conjugates. Our Lx®-based lead ADC outperforms all benchmarks whilst displaying a favorable safety profile, at least in part due to outstanding in vivo stability. In addition, Lx® technology enables highly cost-efficient manufacturing in a very simple plug-and-play manufacturing process. We believe that Lx® technology will enable the creation of ADCs that are effective, safe and affordable.

The antifibrotic potential of a sustained release formulation of a PDGFβ-receptor targeted rho kinase inhibitor

Van Dijk et al. J Contr Release. February 2019.

In this paper, our collaborators describe how controlled release of an Lx^®-based conjugate, targeting the PDGFβ-receptor and carrying the rho-kinase inhibitor Y27632, results in amelioration of liver fibrosis. These results once more demonstrate the feasibility of using Lx^® Linker technology for targeted delivery of kinase inhibitors to treat chronic liver disease.

Folate-dactolisib conjugates for targeting tubular cells in polycystic kidneys

Shi et al. J Control Release. November 2018.

In this study, our collaborators demonstrate targeted delivery of a therapeutic kinase inhibitor to polycystic kidneys using an Lx^®-based conjugate. These results go to underscore the feasibility of using Lx^® Linker technology for targeted delivery of kinase inhibitors to specific, disease-affected organs.

In Vivo Characterization of Platinum(II)-Based Linker Technology for the Development of Antibody–Drug Conjugates: Taking Advantage of Dual Labeling with ^195mPt and ⁸⁹Zr

Muns et al. Journal of Nuclear Medicine. July 2018.

In this publication we describe the behavior and stability of Lx®-based conjugates such as LxC-001 in the living body. In multiple laboratory studies, we show that Lx®-based conjugation does not change the behavior of the trastuzumab antibody. Moreover, the Lx® Linker held drug and antibody firmly together throughout the studies, confirming the strength of the platinum bond.

A novel Platinum (II) Based Bifunctional ADC Linker Benchmarked Using ⁸⁹Zr-Desferal and Auristatin- F Conjugated Trastuzumab

Sijbrandi et al. Cancer Research. January 2017.

In this publication we describe the therapeutic activity of LxC-001. In multiple preclinical models of human Her2-expressing cancer, this Lx®-based antibody-drug conjugate performed better than existing treatment options. LxC-001 achieved complete cures, even when cancer cells expressed low levels of the targeted Her2 molecule.

Platinum(II) as bifunctional linker in antibody-drug conjugate formation: coupling of a 4-nitrobenzo-2-oxa-1,3-diazole fluorophore to trastuzumab as a model.

Waalboer et al. ChemMedChem. May 2015.

In this paper, we describe the development of the Lx® Linker as a simple and versatile means to conjugate drugs to antibodies. The publication describes the heart of our platform technology.

HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects.

Klein et al. Journal of Hepatology. December 2012.

In this paper, our collaborators demonstrate immediate relief of portal hypertension after administration of an Lx®-based conjugate targeted at activated hepatic stellate cells. These results underscore the feasibility of targeting kinase inhibitors to the liver to alleviate the symptoms of end-stage liver disease.

Immuno-PET: shedding light on clinical antibody development.

Van Dongen et al. Cancer biotherapy & radiopharmaceuticals. 2010