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Research & Reviews: Journal ofPharmaceutical Analysis | ISSN : 2320-0812
Euro Pharma Chemistry & Future Pharma 2019
June 27-28, 2019 | Amsterdam, Netherlands
12th World congress on
Joint Event
4
th
Pharmaceutical Chemistry Conference Future Pharma
Volume 08
ThePt(II)-based Lx
®
linker technology for development andproduction
of antibody-drug conjugates (ADCs) with distinguished features
A
ntibody-drug conjugates (ADCs) are a cutting-edge modalities in the
pharmaceutical field because they allow targeted delivery of drugs, which
are otherwise too potent/toxic to be applied systemically, selectively to cancer
cells. However, a greater control is desirable in the stochastic conjugation
technology used to synthesizeADCs. We have recently introduced a metalorganic
platinum(II) linker, an ethylenediamineplatinum(II) moiety called Lx, that allows
to provide ADCs with some unique features, such as targeting the histidine
residues of native unmodified antibodies and an improved hydrophilicity of
synthetic intermediates and presumably metabolites. The general concept of
this novel linker technology (shown in the scheme below) for the preparation of
stable and efficacious ADCs will be presented. The milestones of the Lx platform
development as well as the key features of thus produced Lx-based ADCs such
as serum stability, biodistribution,
in-vitro
cytotoxicity, and in-vivo efficacy
data, along with some recent highlights such as dual radiolabeling of Lx ADCs
with 195mPt and 89Zr radioisotopes, will be presented. Finally, first results will
be shown regarding the manufacturing of our lead ADC, with the corresponding
“semi-final” product being successfully produced at a multi-gram scale and the
original Lx ADC conjugation method successfully technology-transferred to a
CMO for a near-future upscaling and manufacturing.
Biography
Eugen Merkul has completed his PhD with Summa Cum Laude from the University of
Düsseldorf/Germany, and Post-doctoral studies from the University of Antwerp/Belgium,
followed by industrial experience at German and Dutch Companies. He is the Head of
Chemistry of LinXis B.V., an innovative Dutch Biotech Company developing a proprietary
ADC (antibody-drug conjugates) platform technology. He is an author/coauthor of 23 papers in
reputed peer-reviewed journals and inventor/coinventor of 10 patent applications.
merkul@linxispharmaceuticals.comEugen Merkul, Pharmaceutical Analysis 2019, Volume 08
Eugen Merkul
LinXis Pharmaceuticals, Netherlands