Five minutes at CPhI worldwide with …
Chemistry Today/Pharma Horizon: What platform are you responsible for within CordenPharma?
Matthieu Giraud: I am responsible for the Peptides, Oligonucleotides, Lipids & Carbohydrates platform, where we support the customers from Phase I to commercial phase at any scale of development. The idea is to provide a one-stop-shop, a fully integrated solution to reduce the customer’s need for multiple suppliers. To that end, we not only provide the individual bio-organic molecules (i.e. peptides, oligonucleotides, lipids, carbohydrates), but also various conjugates and excipients. In fact, we see that the development of biological drug products as more and more about the conjugation of different biomolecules, in all their possible combinations: peptide-oligonucleotides, lipids-oligonucleotides, carbohydrate-oligonucleotides, lipids-peptides, etc. We can produce the peptide at one of three sites, the oligo at another site, and perform the conjugation at yet a third facility. To complete the full-service model, CordenPharma additionally provides the fill & finish for the final dosage drug product, thanks to our dedicated lines for peptide/oligonucleotide manufacturing.
CT/PH: What application drives these conjugates?
MG: The key problem for oligonucleotide-based therapeutics is to deliver the active oligonucleotide to its site of action in the nucleus or cytosol of cells within tissues. Two parts to this problem have been identified: the first being to convey the oligonucleotide to the tissue of therapeutic interest while minimizing exposure of other tissues; and the second challenge is to convey the oligonucleotide to the right intracellular location. In most tissues neither transport system is capable of efficiently conveying typical nanoparticles (∼100 nm). However in some tissues, such as spleen and liver, there are fenestrations between the endothelial cells, thus allowing egress of larger macromolecules and particles. Endothelial permeability is also increased in sites of inflammation and in some tumors. This last case is a basis of the ‘Enhanced Permeation Retention’ (EPR) effect that has evoked much interest among proponents of nanoparticle-based drug delivery for cancer therapy. The concept is that the increased leakiness of tumor vasculature will allow nanoparticles to selectively accumulate at these sites.
CT/PH: How are new therapeutic areas evolving?
MG: We see a strong demand in oncology, but in fact peptides touch many types of therapeutic areas – Diabetes, immune system, vaccines – it is very broad. Customization and personalization of drugs is increasing and I think that is where we’ll see a lot of growth in the future. Especially in the oncology sector, where physicians look at each patient, sequence the genotype of the cancers, and design a personalized cocktail of peptides which will treat the patient. Each patient has a unique cocktail, which includes from 5 up to 15 peptides. So it is not only about synthesizing all the peptides very rapidly, because these patients cannot wait, but about characterizing the end product, too. This is a real challenge since CDMOs / pharma companies need to provide regulatory agencies with a definite measure of product stability. How do we measure stability on a custom product that has to be shipped tomorrow? How do we ensure low toxicity without any toxicology studies? We do not have months to figure out how stable it is and to check the toxicology of the degradation product.
CT/PH: And how does CordenPharma meet this challenge?
MG: We have to be pragmatic: we have to be able to very quickly supply APIs to our customer, and ultimately a patient, while working with generic analytical methods using the minimum amount of material, and without waiting for full stability studies. Those constraints can only be overcome by a high degree of synthesis and purification.
CT/PH: What kind of expression systems or manufacturing technologies does CordenPharma provide?
MG: Even though our sister company CordenBiochem in Frankfurt (DE) offers contract development of microbial fermentation, and is thus ideally equipped to manufacture large-scale peptides and technical enzymes as well as apply biocatalysis for the synthesis of intermediates and small molecules APIs, we manufacture biomolecules mainly by means of chemical synthesis. Yet we can provide peptides up to 50-100 amino acids long. Our scales go from milligram to tons of GMP-manufactured peptides, thanks to our cGMP facility CordenPharma Colorado located in Boulder, CO (US), which is fully inspected by all major regulatory agencies. This site also has long-standing and unique expertise in peptide precipitation, which is a key technology alternative to freeze drying. For oligonucleotide manufacturing, which is also done at CordenPharma Colorado, we provide up to the kg scale (1.5 Mol/batch), GMP or non-GMP. These processes are very scalable, as we leverage the complete GE Healthcare oligo offering from the OligoPilote to the large OligoProcess, so if a customer asks first for 1 kg of, say, siRNA, and then finds out that they need to produce 100 kg, this is a point where CordenPharma excels.
CT/PH: Is RNA in big demand?
MG: We see more and more demand for RNA products. For modified RNA especially – we can modify the base, but usually backbone modifications are needed to improve bioavailability or stability: here we can perform sulfurization, or insert modified sugars with fluorines or methoxy groups in the 2’ position, for example. Peptide Nucleic Acid (PNA) oligos or Phosphorodiamidate Morpholino Oligomers (PMOs), which show extraordinary in-vivo stability and good affinity for DNA/RNA targets, are also in our platform offering. We have a huge versatility in this sector.
CT/PH: What should we expect from CordenPharma in the future?
MG: When CordenPharma entered the oligonucleotide manufacturing market recently – only 1 year ago – we took it seriously: we acquired experts in the field with over 20 years of experience and installed cutting-edge equipment. In the next few years we will perhaps branch out this piece of the platform, since it is a growing market and we have the competence to make it happen. On peptides, I think the trend is, as I said, towards ease of customization of the end drug product. We are still forming our strategy there, as we continue listening to our customers and keeping informed of market developments, so this is another big focus in the future for CordenPharma.