Animal-free thanks to Scinora

Scinora - a biotech startup

Scinora is a Swiss biotech start-up specializing in the development of animal-free, highly functional cell culture media. Instead of using animal products, the company relies on components from continuously growing human cell lines, which provide specific proteins that are essential for cell growth. Products such as XplaceH or SimplaceX enable stable, safe and ethical cell culture - and are therefore a strong alternative to conventional animal-based solutions. Furthermore, Scinora offers chemically defined cell culture media as a kit for on-site culture optimization as well as cell-specific special media. Scinora thus exemplifies a shift in the life science industry towards greater responsibility and technological excellence.

Interview with Beat Thalmann

Mr. Thalmann, you are the founder of Scinora. How did it come about and what was the trigger?

I need to expand a little on that. It was directly after the practical work for my doctoral thesis in a biopharmaceutical SME that I switched to an academic laboratory for environmental toxicology. I was used to animal-free cell culture media and cell cultures in suspension and was again confronted with serum-containing systems with adherent cultures. In order to primarily simplify the processes and make them more reproducible, it was my task to bring the numerous cell lines into suspension, at least on a trial basis, and if possible to get them animal-free. This worked very well. Subsequently, a first product and a first spin-off were launched with the aim of replacing a widely used product in toxicology - rat liver S9 - with biotechnologically produced alternatives: EWOMIS. Dissatisfied that I was no longer able to work on the other areas of expertise, i.e. cell culture media and cell line development, I started a solo project at around the same time: Scinora. Scinora as a solo project. Scinora has been based in Rafz since 2022, and the EWOMIS portfolio is now also part of Scinora.

Why is animal-free serum a topic in research?

Foetal calf serum, FCS for short, was long considered irreplaceable due to a lack of alternatives. It is obtained in an alienating way from fresh or unborn calf fetuses. In the 1980s, there were increasing efforts to replace FCS with serum-free special media. These were not able to establish themselves due to the price. The BSE cases at the beginning of the 1990s posed an acute threat to biopharmaceutical production. FCS became massively more expensive as it could only be imported from countries without BSE. At the same time, recombinant antibodies were produced using FCS-containing medium. Blood and, to a lesser extent, FCS contain a high proportion of antibodies. This impaired the purification of the human recombinant antibodies. Ultimately, the switch to serum-free, complex and then chemically defined media facilitated the purification of the products and increased productivity. Furthermore, chemically defined media were convincing due to their very high reproducibility. Due to ethical concerns, advances in laboratory meat and mainly the high price, alternatives in standard cell culture are becoming interesting again. In addition, the desire for reproducibility and the switch to human-relevant cell culture, i.e. without the addition of any animal products other than human proteins, is growing. Such developments always come in waves, with price ultimately playing the most decisive role. I am also aware that customers do not want to do without existing protocols and therefore a supplement should work functionally similar to FCS and in combination with the standard basal media. Chemically defined complete media only meet these requirements to a limited extent and are therefore not yet accepted, except for applications in highly specialized, standardized processes. As a result, universal, human-relevant serum replacement supplements with the same handling and effectiveness as FCS are in great demand. With the Simplace product line in particular, in which SimplaceX is the first widely tested product, we are fulfilling the desire for a complete serum replacement and enriching XplaceH with additional vitamins, trace elements and growth factors.

What ingredients do you use to produce the serum you mentioned?

For years Scinora has been using specially developed human suspension cell lines, i.e. cell lines that grow without the use of surfaces or 3D structures in chemically defined, animal-free and protein-free media. These cell cultures are shaken in the bioreactor and achieve cell densities similar to standard cell lines such as HEK293 and CHO. Scinora works with liver cell lines that contain a variety of plasma proteins such as albumin, transferrin and alpha-1-antitrypsin as well as numerous adhesion proteins such as fibronectin, nidogen-1 and vitronectin. These proteins are enriched and purified as a mixture. The resulting XplaceH thus offers numerous functions that are mediated by the FCS.

What has been your biggest milestone so far - and what has been the biggest challenge?

The biggest milestone was the idea itself. Previously, the focus was on the production of HiCultS9, which replaces a preparation for toxicology from rat livers. However, only the cells are required for the production of HiCultS9. After separating the cells, the used medium remains, which was previously simply disposed of. Curious as I am, I wanted to know what the cells produce and started investigations into the protein content and the individual components. This led to the realization that disposal was a waste and that the proteins needed to be purified. At the same time, challenges arose with the chemically defined media in terms of adherent cell culture, as individual customers reported low adherence - interestingly, particularly after using trypsin. By adding XplaceH, adherence and growth could be improved abruptly. One explanation could be the presence of special trace proteins, which the cells otherwise only find in the FCS. This means that each cell line picks the components it needs from the serum or XplaceH.

The biggest challenge was and continues to be that customers are reluctant to switch to serum-free systems. Either the customer is working on highly personalized solutions, where a switch to chemically defined media is possible due to the low process complexity, or they want a 1:1 replacement of the FCS, which is requested in over 90% of cases. The fact that the numerous cell lines worldwide have been treated, cultivated and stored in different ways does not make the situation any easier. Even "the FCS" alone does not exist and has numerous qualities as well as a high batch variability. In most cases, the FCS is then treated with XplaceH and the cells simply die because they cannot cope with the change to something new, as some of them have only been surrounded by bovine proteins for 20-50 years. But I am happy to take on the challenge, as I enjoy my job as a cell whisperer.

What does a typical day look like for you?

Inconsistent. So I simply cannot give you an exact answer to this question. But in addition to the obligatory office work, there is also a lot of laboratory work. However, the ratio and daily working hours change depending on the order situation.

What is special about your products?

Scinora offers numerous solutions to the challenges of cell culture, whether it is chemically defined media or serum replacement supplements. In principle, there is a suitable solution for all cell lines, multicellular constructs and tissues. We have also combined some of the chemically defined media in the SciKit, with which the customer can obtain the desired cell line serum-free with >90% probability. Scinora deliberately relies on a modular principle that allows a high degree of flexibility. Once the right combination of media and supplements has been found, it can be produced on a customer-specific basis. The SciKit is therefore an initial measure to test the needs of the cell line. The XplaceH is of course also included here, which works wonders in most cases. If you only want to have the essence of all products and do without the flexibility, Scinora offers the complete serum replacement SimplaceX. This product contains all the components that cells need for growth in commercially available basal media such as DMEM, DMEM/F12 or RPMI1640.

Does the customer have to pay attention to anything when using your product?

Primarily, the customer must not give up straight away. In most cases, one passage is not enough. It should also be noted that most cell lines have been subject to selection over decades and have therefore adapted to the local conditions. This has also created subpopulations that can slowly overgrow or displace others. If the customer now switches to XplaceH or another product, the optimum conditions are not always present and, in the worst case, the cells die off. In this case, a gradual weaning of the FCS is necessary. Furthermore, some cell lines require additional components, which are shown in SimplacX, as XplaceH as a pure protein preparation does not contain any trace elements or vitamins, for example, and therefore does not offer a complete solution with regard to commercially available basal media. For all these questions and further information, we recommend that all customers contact me to discuss the steps and their individual needs.

What are the scientific or technological principles behind Scinora and what is your philosophy?

For a long time, I was a purist when it came to chemically defined media, but I realized that adapting cell lines and switching from serum-containing to serum-free media is not trivial, especially at the customer's site. The collaboration is based not only on the provision of products, but also on intensive scientific and, in some cases, technological advice. The task of Scinora analogous to the tasks of a therapist for doping or addiction victims. FCS is this drug because it contains a large number of growth-promoting substances that are produced by cancer cells in the early stages of development or in isolated cases. This does not always correspond to the cell's typical environment. The weaning to natural cell-typical growth is a lengthy process.

The aim is a minimal solution, i.e. to provide the cells with everything they need for cell-typical growth, whereby they produce the rest themselves. This approach is by no means new and is already used in the differentiation of stem cells. In many cases, I have observed that the cell lines no longer require external proteins after around 5-10 passages, as they have learned to produce the necessary proteins themselves and have thus also regained the cell-typical properties. This aspect is particularly important for organ-on-a-chip or organoid culture applications. This is where Scinora's products can help.

What plans are you pursuing for the near future - what can we look forward to?

I won't stop at the existing products, but I don't want to give too much away. What will certainly come in the short term, however, are further kit systems. An easy-to-use supplement kit for use in standard basal media will certainly be added to the portfolio. In concrete terms, this means that the Simplace product line will be expanded and continued. The trend is therefore also moving towards easier handling and automation.

Of course, there are always questions of upscaling. I rely on the expertise of partners with appropriate facilities and processes so that I can focus more on the customer and innovation.

What advice would you give to other founders?

I don't know if I can be a good example for founders, especially in this business area. Scinora I wanted to grow organically right from the start. However, it is not easy to grow in the biotech sector without external funding, as development costs are always very high. That's why you always have to be creative and flexible and maintain a keen interest in the subject matter. After many years as a founder and unfortunately also as a liquidator, I would summarize my ideal constellation as follows:

• Scalable product that is easy to understand;
• A founding team of 2-3 motivated people who do not necessarily have to be of the same opinion or have the same background, but always have the same goal in mind;
• Be aware that you have no financial security for 5-10 years and must ensure that the project does not fall apart as a result;
• Focus on strategic partnerships, which take longer to achieve than venture capital, but open up more prospects in the long term. This also means entering into strategic alliances for mutual benefit and being aware that you should occasionally hand over cherished projects to other hands;
• And very importantly, you should let sick horses die a venerable death and not ride them to the bitter end.

This ideal does not completely apply to Scinora in many respects, but I would still do it exactly the same way again.

Outlook