Oligonucleotide stars of the future can be underpinned by the superb Amideus brand from Primopus AG.
August 7th, 2024
Oligonucleotides moving from rare drug provision to wider population usage can be underpinned by affordable phosphoramidite provision. A bold statement becomes real with the 2021 approval of Inclisiran, used for the treatment of cardiovascular disease. A breadth of common diseases, including cardiovascular disease, oncology and metabolic disorders will respond to Oligonucleotide drug provision. Oligonucleotides because of their ability to target ‘undruggable’ protein sites within the human genome are often cited as a cornerstone of the future of personalised medicines.
It is however the potential for treatment of common diseases with its significant technical challenges that offers the most global hope for the unique classification of drugs reaching its potential quickly.
The considerable barrier to harnessing Oligonucleotide comes from scale-up cost, wastage and skill shortages, part of which can be solved if you have an excellent phosphoramidite supply. In the case of the Amideus brand of Primopus, you can in the end leave a lot of the bulk manufacture at source reducing aspects of carbon footprint. A significant challenge for the supply chain is the requirement for high volumes of reactants and solvents needed for the synthesis. It is estimated that there is 4.3 tonnes of waste per kg in Oligonucleotide development. No specific in-depth research has gone into how much of this is the phosphoramidite production, but you might expect it may be very significant.
More... Capacity issues we already know are slowing down the development of Oligonucleotides at the clinical trial level, also ultimately impacting the aforementioned health opportunity for the wider population. Synthesis is usually via solid-state synthesis where the oligonucleotide is bound to a solid support material during the chain assembly. Purification is expensive and uses inordinate amounts of solvent, also producing hazardous waste. Primopus, because of its backward integration into Deccan Fine Chemicals, has the capacity and the knowledge to treat waste at source. Alternative liquid phase synthesis can be an alternative solution for Oligonucleotide production but again costs rise significantly. As the Oligonucleotides industry develops it will have choices to make. Some of these may be temporary. Lypholization is an extremely energy-intensive process involving refrigeration and vacuum systems. It is more efficient than spray drying, but only at a certain batch level. In very high volume situations, it might be that spray drying and accepting a lesser % yield serves purpose. Innovation will catch up. Primopus AG based in Muttenz, Basel, Switzerland is aiming its sites high. Focussing a major part of its strategy via its Amideus brand it squarely sets itself up for considerable challenges in providing phosphoramidites for bulk drug provision with backward integration into India. This helps offset some of the carbon footprint, and while not being a complete answer for innovation, it does give a focus for both the short and medium term. Success in Oligonucleotide production for the wider health market cries out for novel solutions in key intermediates supply, reducing transport, and energy usage while engaging with like-minded science-driven partners. Primopus therefore is ambitious. It seeks to help Oligonucleotide manufacturing innovators by producing phosphoramidites, a key intermediate. Oligonucleotides by their very special nature span chemistry and biology. The opportunity to serve a wider therapeutic need is implicit in this unique category. Affordability and the provision of the Oligonucleotides depend on the practical commercial challenges allied to superb science. Amideus is a valuable brand of Primopus AG, Basel. Less...