Modified molecules that are changing the world

4GENE has developed a platform technology for the glycosylation of active pharmaceutical compounds and other small molecules. The platform serves as an “enabling technology” for developing a wide variety of applications.

Heiko Adamski 4Gene

Heimo Adamski, CEO 4Gene GmbH

„Currently, we have a portfolio of more than 100 molecules that we have glycosylated, covering different market segments.“

Heimo Adamski
CEO 4Gene GmbH

4GENE was founded 5 years ago as a spin-off of the department for “Biotechnology of Natural Products” at the Technical University of Munich and moved to the Freisinger Campus of the Innovation and Start-up Center for Biotechnology (IZB). Under the direction of co-founder and managing director Heimo Adamski, what began with the refinement of fragrances and aromas has now become a platform for “improved molecules” that are used in the fields of cosmetics, pharmaceuticals and industrial safety. An interview about inspiration from nature and the ability to think outside the box.

Mr. Adamski, you are with 4GENE on the IZB’s Freising campus. What is special about this location for you?
This location is interesting for us due to two aspects. On the one hand, we come from the TU Munich, from the Department for Biotechnology of Natural Substances, and are now very close to the place where 4GENE was born. Due to the physical proximity, we can easily maintain contact and networking with various institutes at the Technical University of Munich. The second aspect is more of a problem and affects start-ups in the biotech scene in general: there is simply not enough suitable laboratory space for spin-offs and start-ups. You can find a laboratory with 2,000 m2 of space on every street corner. But start-ups don’t want to play football, they want to work, and for that they usually need smaller spaces to begin with. The IZB is perfectly suited for this, and we are very happy that we have found a home with you and have settled in.

When you review your time at the IZB, which events will you always remember?
I can certainly list many highlights from the 5 years that 4GENE has existed. The first milestone was of course leaving the university, which was a wow experience for all of us. Then followed the first talks with investors in order to even manage to equip the laboratory with the essential equipment. For many colleagues from the natural sciences, such an investment agreement is a completely new experience, and very few have experienced it before. Signing the first investment agreement is an inspiring event. And then, of course, the opportunity to set up your own start-up and bring it to life, in other words to further develop the things that you basically developed at university and turn them into successful products. This is one of the most exciting things you can do in business life.

How would you explain to a child what 4GENE does?
Imagine it is 12 noon in summer and you are walking across a meadow full of flowers. Your nose picks up so many scents and aromas that you can hardly process and distinguish them, because the plants give off these substances to either ward off predators or to attract pollinating friends. But if you walk the same way across the same meadow at midnight? Then you don’t smell anything!

The reason for this is that the plant produces substances called metabolites that are very small and therefore volatile. To store these volatile metabolic products, it attaches a sugar molecule, a molecule of glucose, to these substances, which binds to them and means they can no longer be smelled. They also become more stable, more soluble in water and can be better stored by the plant. Then, with the first rays of the sun, this process is reversed. Plant enzymes ensure that the glucose is split off again and the volatile starting material is released and can be smelled again. In principle, we do exactly what the plant does.

How does it work technically and in which areas do you use your platform?
This attachment of sugar molecules is called glycosylation. We use the enzymes required for this in a biotechnological process and are therefore able to produce glucosides from specific starting materials, so from small molecules. We currently have a portfolio of more than 100 molecules that we have glycosylated and that address different market segments.

When choosing the market segments to be actively worked on, we looked at what regulatory hurdles exist in which area and asked what resources do we have as a start-up? On this basis, we have decided that we will initially focus on the cosmetics, pharmaceuticals and industry segments, since this is where we can bring our products to market fastest and where glucosides can be used in products.

With “Sniff & Save” you marketed your first product for industry. Was there no fire protection before?
Yes of course. There are many legal requirements and regulations. However, our product is analogue, meaning it is very different from the digital systems existing and used today. With Sniff & Save, there can be no power outage or hardware breakdown. The basic principle is the same as we use in our technology platform in the other market segments: we take a noticeable odorant, in the case of Sniff & Save a smoky, intensely unpleasant one, and process it with our platform. This substance is then in a bound – non-smelling ­­– stable form. We apply this stable version of the warning substance to a carrier material, for example a sticker. Chemically, this bound version has the property that heat acts as a trigger to break the bond between the scent molecule and the sugar molecule.

This means that if this sticker is stuck on a piece of equipment that normally operates at a temperature of 80-90 degrees, then nothing will happen. But when the device starts running hot and reaches a defined temperature range, say 130 degrees, then this smoky, intensely unpleasant odor is released and alerts people nearby. Of course, the machine would not actually catch fire at 130°C, only much later. But that means, two hours before it actually catches fire, it already smells as smoky as if it were burning. This gives people the chance to turn off the equipment and stop production and so prevent a fire and further damage.

Infografik 4Gene

Technology platform for the glycosylation of small molecules

What advantages does 4GENE’s platform offer the pharmaceutical sector?
Let me explain this with an example: Many active pharmaceutical compounds are poorly soluble in water and are therefore offered as tablets. But there are many people who have problems with swallowing and cannot take pills, or can only take them with aids such as a gel. For this reason, many people do not take the dose that is necessary or prescribed. Water solubility can be significantly improved by glycosylation of the active ingredients. So with our technology, for example, it would be possible to develop an active ingredient as a drink. For the benefit of patients.

To demonstrate that this actually works, we took paracetamol and glycosylated it as a proof-of-concept. This is of course a poor example for marketing, because the price for paracetamol on the market is so low that even a refined form would be difficult to market. But what we did with paracetamol can be taken as a blueprint for other active ingredients that would be economically interesting. We are currently working on specific projects with partners and industry.

Are you now going into drug development yourselves?
Pharma is an interesting segment for us, but we will never be the ones developing the product and conducting the clinical trials. Our core competence lies in the innovative application of our technology platform. We are the technical innovation team bringing new technology to the pharmaceutical companies and CDMOs.

As in the other market segments, we either offer our customers one of the molecules from our portfolio, or the customer comes to us with their own molecule and commissions us to analyze what advantages glycosylation of the molecule could bring. As a technology provider, we usually conduct a feasibility study for the specific active ingredient and, in a second step, check whether this also works in large-scale production and whether it makes economic sense. Then the customer receives a small sample for the laboratory, then their pilot quantity and then we license the processes to the customer, who can then produce the active ingredient themselves.

In which of these market segments do you see the greatest potential for 4GENE?
We have been actively marketing our platform since January 2022. From a purely economic point of view, the pharmaceutical segment is interesting with regard to possible license fees. But pharmaceuticals is also a long-term business, so you need patience.

We also see great potential in the industrial environment; especially with regard to e-mobility, there are already talks with the automotive industry about our Sniff & Save early warning system for overheating in battery systems.

In the field of cosmetics, the trend is towards natural products, probiotics and postbiotics. It’s all about the skin microbiome. Glucosides, especially those used in the cosmetics field, have the pleasing property of not only enhancing fragrances and aromas, but also making cosmetic ingredients more skin-friendly.

How is 4GENE financed?
4GENE is classically financed by VC. Initially, we acquired a seed investment with which we completed and paid for the development of the platform. Now we are in marketing and need to grow to take advantage of market opportunities. Indeed, the topic of glycosylation is gaining in importance, and we want to transform the growing market interest into corporate growth and profitability.

To this end, we want to expand the organization in the area of ​​business development. To grow purely organically would be too slow for me personally. We want to grow more rapidly and seize the opportunities in the market, which is why we are currently working on another round of financing in order to implement the growth strategy in the context of an equity investment.

What do you do to find and retain new employees for your growing start-up?
We follow the principle: train your people so well that they will always find a job in industry, and then treat them so well that they stay with you. That’s very philosophical, but in concrete terms it means that we promote the talents of the individual and also enable our employees to think outside the box and look into other areas that interest them.

When it comes to new employees, the proximity to the department from which we come naturally helps us. We have a good pool of scientists who are familiar with our topic. It is currently rather difficult to find specialists in the field of process development and process technology. With a great team, we built a biotechnological platform in about a year and a half, which is still scalable. For me, that is really world class and a good argument for the spirit that new employees can expect from us. In addition, we created and implemented an employee participation program in the summer of 2022.

What else would you like to achieve with 4GENE?
Today, our technology platform offers us enormous flexibility that we didn’t have at the beginning. We currently have an inquiry from a new market segment that we would never have thought about 2 years ago. The topic of glucosides as a technology for improving, refining, and modifying molecules has meanwhile gained momentum in various market segments.

With the positioning of the technology platform as “enabling technology” for several market segments, we have found our niche where we feel very comfortable and are successful. This gives us the opportunity to create value and bring benefits.

We want to offer our employees a personal and professional environment so that they enjoy doing what they do. They should have a long-term perspective with us and be able to contribute to the development of the company.

What advice would you give to young entrepreneurs?
The TOP 3 of good advice are old friends:

  • Make your teams as heterogeneous as possible right from the start. Not only do you need someone who can solve difficult problems in the lab, you also need someone with an eye on the numbers and someone who keeps their nose in the market wind.
  • Reach out to potential customers very early on and take them with you as you develop your product. Many start-ups don’t do this because they are afraid that too many details will be revealed before they’re finished. But the customers need be informed because they can provide important feedback from the market. What does the market really need, what should the final product be able to do? You’re not giving away secrets out there, you’re gaining partners who will help you to be faster and better than the others.
  • Last, but not least: Business Plan, Pitch Deck, and Investment. Again, you must focus on the essentials. Take part in as many competitions as possible (PlanB Straubing, Munich Business Plan Competition, Science4Life, …). The feedback and experience from these competitions help with good financing.