Our immune system protects us against infections caused by parasites, fungi, bacteria and viruses. However, this defense method can sometimes work against you. With an organ transplant, for example, you want a patient to have specific tolerance for the ‘strange’, new organ. Whereas in the case of tumor cells you want to generate an effective immune response.
The name says it all. Startup Trained Therapeutix Discovery (TTxD) wants to train our immune system with nanobiological therapy to combat diseases that are difficult to treat.
Joost Kreijtz is Chief Development Officer at TTxD. He will join the company in 2021, after a PhD in virology at Erasmus MC, postdoc positions at Erasmus MC and LMU (Munich, Germany) and various positions in the biotech industry. “Our goal is to regulate the immune response. We do this with nanotechnology developed by TTxD founder Willem Mulder. In the bone marrow, white blood cells are produced by progenitor cells. We take control of this production process, as it were. In this way we can ensure that the immune system is given a tolerant status, or the opposite of that.”
A (short) lesson in immunology
Freshen up. Our immune system consists of two parts. The innate part – a kind of first line of defense – is the first to try to clear an infection. When the threat remains, the adaptive part takes over the defense.
Then there’s immunological memory: the immune system’s ability to remember exposure to a particular antigen so that it can respond more quickly and efficiently upon a second exposure. In short, it ensures that a patient is better protected.
The start-ups and spin-offs of TU Eindhoven
Eindhoven University of Technology (TU/e) is a breeding ground for new ideas that rely on scientific research. Sometimes these ideas grow into spin-offs and start-ups. This brings scientific research one step closer to society. Every month, in collaboration with The Gate and TU/e, Innovation Origins puts an innovative company in the spotlight that results from scientific research. This time: Trained Therapeutix Discovery.
Read the other stories in this series here.
Trained Immunity
It was long thought that immunological memory resides exclusively in the adaptive immune system. Research by TTxD founders Mihai Netea and Leo Joosten showed that the innate immune system also has memory. We call this ‘trained immunity’.
The drugs that TTxD develops consist of nanobiologics. In other words: molecules that occur naturally in our blood. “That is naturally safer. The core of our medicine consists of fats of which the active substance is an intrinsic part. To make it into a solid skeleton, it is surrounded by a large protein. This combination ensures that the particles are safe and accepted by the body. In addition, they accumulate in the bone marrow, where our progenitor cells generate white blood cells.”
By having the body produce immune cells that are more active – or, conversely, calmer – TTxD aims to let the body fight diseases itself. “We are not going to look at the bottom of the stream to see what we can do. Our medicine works upstream. We want to tackle ‘wrong’ cells at their origin, in the bone marrow.”
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Two candidates
The biotech start-up is working on two candidates. The first candidate activates the immune system so that it, in combination with other drugs, causes a tumor to shrink.
Many immunotherapies are available, but they only work in a subset of patients. This is partly due to myeloid cells that form a kind of shield around a tumor, so that it can continue to grow and the immunotherapy does not reach the tumor. TTxD wants to manipulate those cells in such a way that they support the immune system instead of the tumour.
“The goal is to work synergistically with other drugs to more effectively treat different types of cancer,” Kreijtz explains.
The second drug candidate should inhibit inflammatory diseases when the immune system’s response is too intense, such as in infectious diseases (e.g. Covid-19) or organ transplants.
“We are not going to look at the bottom of the stream to see what we can do. Our medicine works upstream. We want to tackle ‘wrong’ cells at their origin, in the bone marrow.”
Joost Kreijtz
Pioneers
TTxD is the first company to combine nanotechnology and trained immunity put together in a medicine. That brings a lot of uncertainty. It is a major challenge to maintain long-term financing, says Kreijtz. “We talk a lot with investors about what to expect. And we show a lot of data. This gradually reduces the risk and increases the chance of success.”
With a team of about twenty people (internal and external), TTxD is now focusing on the development of the two drugs, their mode of action and safety, and the scalability of production. After this, the medicines can be tested in the clinic.
It will take at least another five years before the drug can actually enter the market. Kreijtz had to get used to the long process that precedes the development of a medicine. “As a biomedical scientist, I was trained to work in the lab where you can see the results of your work fairly immediately. Now I almost always sit behind my desk. People now look at me strangely when I walk into the laboratory (laughs).”
As a CDO, Kreijtz is involved in finding the right dose to presenting it to investors. His range of tasks is varied, but that is exactly what he likes about it. He long saw his “ADHD nature” as a weakness – in the scientific world he was trained as a specialist – but now he embraces it. “One day I’m looking for the right bottle for our medicine, while the next day I can immerse myself in a scientific discussion about the effect of our medicine against cancer. “It gives great satisfaction that we, together with our entire team, take a medicine a little further towards the patient every day, in order to ultimately make a difference there.”
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