Can you tell us about Sekisui XenoTech and the products and services the company offers to the pharmaceutical industry?
Sekisui XenoTech, LLC is a global Contract Research Organization with unparalleled ADMET / DMPK / DDI experience and proven expertise from discovery through clinical support, providing cell and tissue-based products, screening, radiolabeling, chemical synthesis, in vitro ADMET and pharmacology, in vivo ADMET and QWBA, metabolite ID and production, bioanalytical services and consulting. Our product selection includes a wide-range of high quality, standard and unique reagents, such as subcellular fractions, NPCs, hepatocytes, cell lines, tissue samples, recombinant enzymes, substrates and metabolites. Sekisui XenoTech also regularly prepares and delivers custom-designed products and services in response to client requests.
Our consultative approach and dedication to quality has made us a trusted partner for 35 of the top 40 pharmaceutical companies worldwide.
Regarding products offered, can you tell us specifically what lysosomes are and how they can be used to be a more cost effective and accurate in vitro test system to monitor the stability/catabolism of targeted biotherapeutics that enter cells through the endosomal-lysosomal pathway?
Lysosomes are membrane-bound cellular organelles that are the site of degradation / catabolism of extracellular substrates (endocytic pathway) and intracellular substrates (autophagy pathway). Lysosomes contain a multitude of acidic hydrolytic enzymes and have isopycnic densities similar to mitochondria. Tritosomes are lysosomes isolated from Tyloxapol-treated animals for improved separation of the organelle from the mitochondria, and consequently, high specific activity of its catabolic enzymes.
Considering their unique pH and the presence of a variety of catabolic enzymes, therapeutic strategies are being designed to take advantage of lysosomes as the primary site of catabolism/activation for targeted biopharmaceuticals that enter cells through the endosomal-lysosomal pathway, such as ADCs, siRNA/RNAi molecules, immunotherapeutics, biodegradable copolymers and nanoparticles, etc.
Lysosomes are an important in vitro diagnostic tool because they are the most representative test system available, as multiple enzymes or physical characteristics are very likely to have a synergistic effect on the stability of biomolecules. For instance, ADCs are likely to have a heterogeneous drug antibody ratio (DAR) and targeted modifications that stabilize the compound while in circulation. Differing amounts of drug, conjugated to various regions of the antibody, with assorted types of linkers and modifications of the primary structure of the antibody will undoubtedly affect ADCs’ stability. Therefore, it is beneficial to conduct initial screens with this simple and most in vivo-relevant system available.
Why should a pharmaceutical company choose your company’s lysosomes and associated services over another company’s? What benefits do you provide to a potential customer that other companies don’t?
Before we released these test systems, there was not a high-quality, specific, relevant, easy and ready to use, in vitro test system to monitor stability/catabolism of targeted biotherapeutics like there was for small molecule compounds. However, purified hepatic lysosomes show superior lysosomal enzymatic activity when compared to liver homogenate or S9 fraction, and are likely to be more predictive than individual purified proteins.
Sekisui XenoTech offers human liver lysosomes and rat liver tritosomes as standard products, and other custom preparations can be made ondemand. Our lysosomes and tritosomes contain high concentrations of lysosomal degradative enzymes, and we can also provide a 10x catabolism buffer that has been formulated and optimized to extract the most in vitro catabolic performance.
What assurances can you give a pharmaceutical company that wants to use your products not only in the United States but worldwide? What regulatory assistance can you provide for companies with international operations?
We have extensive experience shipping cellular and tissue-based products and performing research services for customers around the world. Sekisui XenoTech has facilities in North America, Europe and Asia as well as a global network of partners and distributors. We also employ strict quality standards, satisfying the expectations of all applicable regulatory agencies. The guidance of our technical support, scientific and consulting teams spans multiple disciplines and is available to all of our customers.
Looking ahead are there specific products and/or services that you will be adding to your portfolio to further enhance your company’s value to current and future clients?
We monitor regulatory requirements and research needs on an ongoing basis to provide the most effective assays and products to help our clients develop safer therapeutics and avoid delays in drug approval. For instance, lysosomes, genotyped cellular test systems, and disease-diagnosed tissue and cells are just a few examples of recently released products for which we have seen a need. We have also been adding in vivo assays that complement our core in vitro capabilities and will be providing additional in vitro toxicology studies and regulated bioanalytical assays in order to maximize convenience and efficiency for our customers.