For a long time, it was mainly used as a model system for basic research – archaeon Sulfolobus acidocaldarius. It is one of the extremophilic microorganisms that thrive in very hot, acidic conditions and can be an extremely valuable natural resource. Dr. Julian Quehenberger, CTO at the Austrian Vienna University of Technology spin-off NovoArc, researched the microorganism in his dissertation with Professor Oliver Spadiut at the same university and came up with the idea of using it for industrial purposes. In 2021, Quehenberger and Spadiut founded the biotech company NovoArc together with Dr. David Wurm. They succeeded in commercializing the idea with spin-off fellowship funding from the Austrian Research Promotion Agency (FFG). Here is CEO David Wurm in an interview with Innovation Origins:
What’s wrong with using syringes?
Many active ingredients must be injected due to their instability in the stomach and poor absorption in the body after oral administration. Currently, chemical coatings are used to protect the active ingredient in the stomach, but these often take up a large portion of the entire tablet. In some cases, active ingredients with poor bioavailability are administered to patients in extremely high dosages so that the body can absorb a sufficient amount. This leads to severe side effects, such as with antibiotics, which can destroy the intestinal flora. It also places a heavy burden on the aquatic ecosystem. For example, infertility of fish occurs due to the excreted hormones of the birth control pill.
How does the microorganism solve this problem?
We use a biological envelope of lipids – called liposomes – to protect different active ingredients from degradation in the stomach and increase absorption in the intestine. The lipids originate from the cell membrane of the extremophilic microorganism and serve as a biological barrier against the harsh environmental conditions in its natural habitat. The use of these lipids was established several years ago and has been successfully tested in numerous in vivo studies for the delivery of insulin, antibiotics, cancer therapeutics and other agents.
There are no products with this technology on the market yet because of the poor availability of the lipids required for this purpose. So far, they could not be produced in sufficient quality and quantity. After years of research, we have succeeded in establishing a production process that solves this problem. This means that the technology can now finally be used in the pharmaceutical sector.
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Where does this innovation fit into the research environment?
There are currently various approaches to replacing syringes with tablets, but they always involve a number of disadvantages. Yet, the topic is extremely important. After all, more than 20 percent of the entire population is afraid of injections, and many people even faint briefly when injections are administered.
What challenges did you face in R&D?
The biggest challenge was to develop a defined production process for the required lipids. We produce these substances via a biotechnological process using archaea. These archaea grow very slowly in nature and require very complex conditions. Cultivating them in a defined, controlled laboratory atmosphere in a reproducible and scalable way was no easy task. This is where our know-how from bioprocess development and many years of experience in the field of pharmaceutical production processes came in handy.
To what extent is the product already marketable?
The pharmaceutical market is very sluggish, which is why we are all the more pleased that we already have several collaboration agreements with pharmaceutical companies and have already sold our product to them. Since we are an innovation-driven company, we want to constantly develop our product further. We are currently working on special lipid mixtures that we are adapting to specific active ingredients.
Also, in addition to the field of oral drug delivery, we would like to get involved in the field of dermal and nasal drug delivery.
Can you describe your business model?
Our core business is to sell lipid mixtures and pure lipid fractions. Before we sell our products to customers, we often do paid proof- of-concept studies with pharmaceutical companies to show that their active ingredients can be packaged into our liposomes. In addition, the liposomes must be characterized physicochemically, in vitro or in vivo. If this initial study is successful, the process is optimized in a proof-of-process study. This generates more data to better estimate how much active ingredient is absorbed by the body and how long it takes. We then produce the lipids for clinical trials – and in the final step for the pharmaceutical market. We either transfer the encapsulation step of the active ingredients to the pharmaceutical partner or carry it out together with an established formulation company, such as Polymun, with whom we are already in contact.
To what extent is the product environmentally friendly?
An additional major advantage of our technology is the stabilizing effect of our lipids on the active ingredients during storage. Normally, many active ingredients must be stored at temperatures as low as minus 70 degrees Celsius. This is associated with high costs, a large logistical effort and high energy consumption. Our lipids should make it possible to store many active ingredients at room temperature. This in turn will significantly reduce the CO2 footprint. It will also make it possible to provide medical care to people in remote areas.
Are you also planning to use the microorganism for the production of green hydrogen?
We also plan to use the stable lipids of Sulfolobus to develop novel mini-power plants for the production of green hydrogen (H2). H2 is a carbon-free alternative energy carrier and is being touted as the sustainable fuel of the future. This is due in no small part to its high gravimetric energy density (i.e., how much energy is stored per unit of weight of raw material).
But most H2 used today is derived from non-renewable sources such as natural gas or coal. Only a small fraction, around 4 percent, is produced from water by electrolysis. But electrolysis is only sustainable if the required electricity comes from renewable energy sources, such as wind or solar energy – and this is only true for 5 percent. New, sustainable methods for the production of green H2 are therefore in great demand.
One possible green process for producing energy or hydrogen is semi-artificial photosynthesis. In this process, the enzymes responsible for photosynthesis from plants or microorganisms are used in photoelectrochemical cells. These enzymes are embedded in membranes in their natural environment. If you want to use them efficiently for a long time, you need to embed them in such an environment to stabilize them.
Recently, these enzymes have been successfully incorporated into conventional liposomes, but this served a purely basic science purpose. Conventional lipids are not stable enough to withstand the high temperatures and oxygen which are required for photosynthesis.
We want to produce green H2 sustainably from light and water in stable mini-power plants. To this end, we will biotechnologically extract the photoactive building blocks in CO2-negative processes and package them in NovoArcs stable lipids. We will submit a corresponding FFG project application in 2022.
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