Cutting-edge biotech on demand from Vienna

Programmable bacteria and genetic scissors create the basis for Covid vaccines and personalised cancer therapies.

The history of Biomay AG began in the 1980s, when the company was mainly involved in allergens and allergy therapies. Since 2019, the company has focused exclusively on contract manufacturing of biopharmaceuticals as a CDMO company (Contract Development and Manufacturing Organisation). With a focus on plasmid DNA, messenger RNA (mRNA) and recombinant proteins, the company, based at Seestadt Aspern in Vienna, is at the spearhead of the latest developments in the biotech sector. Biomay produces personalised cancer therapeutics and a starting material for Biontech/Pfizer’s mRNA vaccine against Covid-19. Biomay CEO Hans Huber gives us a behind-the-scenes look at cutting-edge biotechnology and its future.

Could you briefly explain your business model?
Hans Huber: Biomay AG is a biopharmaceutical company. We deal with biotechnology in the context of the pharmaceutical industry. However, we are not active in the research industry, but in the manufacturing industry. A researching pharmaceutical company is not automatically a company that is also good at producing its own developed products. That is our job. We are a contract manufacturer for the production of biopharmaceuticals – such as recombinant proteins, messenger RNA and plasmid DNA – using biotechnological methods. Our microorganisms, mostly bacteria, are the cell factories. We use the synthesis and production capacity of bacteria, the workhorse being Escherichia coli (E. coli). These E. coli cells produce recombinant proteins, DNA and the like for us.

Do pharmaceutical companies come to you with their developments?
Huber: Pharmaceutical companies, biotech companies and also start-ups usually approach us with a precise definition of their product, but they usually only have a rough idea of how to produce it. We have this production know-how, and we use it together with our experience to manufacture products for other biotech companies.

Your company history already began in the 1980s.
Huber: The company was actually founded as early as 1984, making Biomay one of the oldest genuine biotech companies in Austria. The founding focus was on allergies and the production of allergens using biotechnological methods. In the process, molecular biology and genetically modified bacteria produce a so-called recombinant allergen, such as the birch pollen allergen, for research purposes. That was long before my time. We still sell allergens today, but it has become a niche business. Then, Biomay got involved in the product development of vaccines against allergic diseases. We started this business line in 2009, when we manufactured our own clinical trial products in our own facility. Subsequently, the business idea arose to use our production facilities for other companies as well. As a result, Biomay became profitable in the mid-2010s. We then decided to sell the allergy product division and be a pure contract manufacturer. After a parallel operation, we have been a pure CDMO company, a Contract Development and Manufacturing Organisation, since 2019.

Biomay deals with three product groups. What are the recombinant proteins?
Huber: Proteins are the molecules of life and often involved in the course of diseases. That is why certain proteins are generally important for therapies. Biomay produces such proteins recombinantly. Here is an example: We know insulin from diabetes therapy. Diabetics lack this insulin protein, their body cells cannot produce it themselves. A diabetic must be injected with insulin. In the past, this therapeutic insulin was extracted from the pancreases of pigs. At the end of the 1970s, a method was developed to produce insulin artificially using cloned microorganisms (recombinantly). In this process, bacterial or yeast cells are reprogrammed to produce insulin inside their cells. Since then, production processes have been used in which Escherichia coli bacteria or Saccharomyces cerevisiae yeast fungi are used to produce insulin biotechnologically so that it can be used as a drug. We are not using this process principle for insulin, but for novel protein products. We reprogramme bacterial cells to produce a certain protein, cultivate them in a bioreactor to multiply them. Then the cells are broken open, usually mechanically, and the protein is extracted from inside the cell. This active agent is our product, which we supply to pharmaceutical companies and which they fill into a final container.

Another business field is plasmid DNA.
Huber: In the past decades, the novel field of gene therapy emerged. We produce DNA in the form of ring-shaped plasmids. This plasmid ring is also found in the Biomay logo. The plasmids are multiplied in bacteria. The resulting DNA can be used in many ways. It can be used directly as an active agent, because the proteins ultimately derive from DNA. If a plasmid is administered to a patient, he produces the protein himself after the intermediate step via the mRNA. Therefore, you could treat a diabetic with a corresponding plasmid and he produces the insulin with the help of his own body cells. This is how the basic principle of gene therapy and DNA vaccination works, in which the patient is not given the therapeutic protein itself, but the genetic information for the production of this protein. However, the plasmid DNA can also be used as starting material for a vaccine. This principle has been widely known since the Covid pandemic.

Plasmid DNA is related to your third product group, messenger RNA?
Huber: The mRNA is the third important class of molecules that we produce. The fundamental biological information in all cells is DNA, the genetic code. DNA is transcribed into mRNA, messenger RNA. The messenger RNA is then translated into the protein. This is the fundamental, biological principle of the flow of genetic information: from DNA, to mRNA, to protein. Plasmid DNA is also used for biotechnological production of mRNA. In this process, a piece of DNA, the DNA template, is transcribed in vitro in the bioreactor. The process is called in vitro transcription of RNA. So, we produce plasmid DNA, prepare it so that it is suitable as a starting material for mRNA production, and deliver it to the customer. During the pandemic, we supplied Biontech/Pfizer mRNA vaccine with a starting template for their mRNA vaccine against Covid.

So, the Covid vaccine actually comes from Biomay?
Huber: I have to put that into perspective. Only part of their total requirements came from us, we were not the only supplier. But a substantial part of the starting material for the production of the vaccine came from Biomay.

But in all this, the mRNA does not interfere with human DNA?
Huber: No, because this path is only possible from DNA to RNA; it doesn’t work the other way around, at least in the human cell. The RNA is not incorporated into the DNA.

Do you also use the famous gene scissors in production, which have been causing a stir for some time?
Huber: Simple types of gene scissors, which are only used to cut DNA, have been around for some time. Biomay is indeed involved in those novel gene scissors that received a Nobel Prize in 2020, but I can’t say too much about it for reasons of secrecy. I can say this much though: We are making the gene scissors CRISPR/Cas9 for a company. Cas9 is a smart gene scissor that becomes individually programmable by a short RNA code (‘guide RNA’). This makes it possible to cut, insert or correct something at very specific points in the genome. This can be used, for example, to correct a disease that is based on the mutation of a single protein, such as when the protein is missing or defective. This involves taking spinal cord cells and then using the gene scissors to perform what is known as gene editing.

Biomay is active in many more areas than popularly known.
Huber: The customer doesn’t always have an interest in project details leaking out to the public, or they like to be in charge of communication themselves. We are also bound by confidentiality agreements. Publicity is not our highest priority. However, we are already very proud of our gene scissors because this project is relatively far advanced and will soon be approved for the market.

You work with E. coli bacteria. That probably rings alarm bells among many people.
Huber: E. coli is a bacterium that exists naturally in the intestinal tract of higher organisms, such as vertebrates. It is a certain component of the natural intestinal microbiome, which is why it is also used as a faecal indicator in drinking water analysis. There are also pathogenic, i.e. disease-causing, E. coli strains that can cause various small intestinal diseases. We do not use these pathogenic strains, and our laboratory strains do not possess these pathogenic properties. They are all in the lowest, i.e. safest, biological safety level and are ‘good’ E. coli bacteria, so to speak. As early as the 1970s, the first protein was cloned using E. coli, and the bacterium is still one of the workhorses in biotechnological production. E. coli is one of the best-studied organisms there is, easy to handle, and it has been around for many years.

How did your relatively new location at Seestadt Aspern come about?
Huber: We didn’t complete and move into the facility here until December 2021, although our production facility in Lazarettgasse in Vienna still exists. Here, the premises are much larger. We were made very welcome at Seestadt from the start and have established a small biotech hub here. Across from Biomay, a Hookipa Biotech site will be built, and Takeda Pharmaceutical will also settle nearby

Is there enough young talent in Austria in your field?
Huber: It used to be easier to find good and enough staff, especially when a company is growing like ours. In Austria, and especially in the Vienna area, there are traditional universities on the one hand, and relatively new universities of applied sciences covering biotechnology, bioengineering and others on the other. The offer of practical and scientific training opportunities and the number of graduates with good qualifications is there. There is also a labour market, there are global corporations and start-ups operating in Vienna.

Do the conditions for Austria as a business location need to be improved?
Huber: I don’t want to complain, because the City of Vienna is doing a lot for the life sciences sector and for settlements. But there are other provinces in Austria that neglect this or set other priorities. Lower Austria has also done a lot in the past decades, biotech hubs and life sciences centres have been established in Tulln, Krems and Klosterneuburg. As I mentioned, the range of educational institutions is large, and the base and know-how of graduates is available. Companies are supported at the start and in the early phases of research. When it comes to the clinical phases and towards market launch, the capital market in Austria is rather underdeveloped. However, we are not affected by this, because we want to grow organically under our own steam and not take in external investors. We have managed to do this very well so far.

What can we expect from Biomay in the near future?
Huber: We are active in the manufacturing sector and can implement innovations within the scope of the products we manufacture. But we are driven by the innovations of our customers. Here I definitely see revolutionary developments, such as in gene therapies, Covid vaccines, mRNA products or gene editing with CRISPR/ Cas9. We are living in exciting times. In addition, there is the personalised production of active agents. Here, our customer designs a patient-specific plasmid or vaccine, and we produce a batch for just one tumour patient. These are highly innovative therapies and products. In the future, the field of synthetic DNA could become interesting, which is no longer produced biotechnically, but precisely enzymatically-synthetically, which brings a number of advantages. That seems to be the next big step. In the next five years, we will see products that we don’t even know about today.