Kira Astakhova. Foto: Bax Lindhardt

Startup is developing treatment of rheumatoid arthritis

Monday 08 Jun 20
by Morten Andersen


Kira Astakhova
Associate Professor
DTU Chemistry
+45 93 51 35 52

About Kira

At the age of only 31, Kira Astakhova (left) took up a position as Associate Professor at DTU Chemistry in 2017. She completed her studies in Russia and Denmark.

Kira Astakhova conducts research into synthetic biology, where she moves at the intersection of chemistry and biology. It has taken eight years of research to arrive at a drug candidate against rheumatoid arthritis.

Doctors can currently only alleviate the symptoms of rheumatoid arthritis. The start-up Ibio Tech is working on a drug which may lead to treatment of this incapacitating disease.

When, in 2018, tennis star Caroline Wozniacki revealed that she suffers from rheumatoid arthritis, it helped put the spotlight on the disease. Around one per cent of the world’s population suffers from the disease, which manifests itself in the form of swollen, inflamed, and aching joints. Many patients gradually become disabled and have reduced life expectancy. For unknown reasons, the disease is particularly widespread in Scandinavia. Based on blood tests and people’s experience of pain in the joints, it is estimated that four per cent of the Scandinavian population are at risk of developing the disease.

Rheumatoid arthritis is an autoimmune disease. This means that the body is attacked by its own immune system, which attacks the cells in the joints. The reason why the immune system selects a completely wrong target is not known. This makes it difficult to develop any efficient medication. In the last 30 years, however, a number of products have been launched on the market. A joint feature of these drugs is that they alleviate the symptoms and delay the deterioration of the patient’s condition. But the start-up Ibio Tech has now patented a product that has the prospect of becoming a treatment for rheumatoid arthritis in so-called ‘poor responders’, that is patients who do not respond to the medication currently available.

The start-up is exploiting that rheumatoid arthritis is precisely an autoimmune disease.

“Our product is able to ‘recruit’ immune defence cells that transport the medicine to where the disease is manifesting itself. That is in the synovia (the fluid in the joints). This means that our product is both more efficient and has fewer adverse effects than other products which are released throughout the body,” says founder of Ibio Tech and Associate Professor at DTU Chemistry, Kira Astakhova.

Effective for those worst affected
The current products on the market are so-called disease-modifying anti-rheumatic drugs, of which MTX (methotrexate) is today the most widely used. However, MTX only has an effect on half of the patients with rheumatoid arthritis. Unfortunately, doctors are unable to predict which patients will benefit from the product. It must therefore be administered to all patients. A switch can subsequently be made to another preparation for those patients who do not benefit from the drug. Approx. 20 per cent of patients experience no effect, regardless of which of the currently available products they receive.

With Ibio Tech’s product—which so far only bears the laboratory name ANC0031802—it is possible to identify in advance the patients who will benefit from the treatment. This is done based on a blood test. The majority of rheumatoid arthritis patients have elevated levels of a particular type of antibodies—ACPA—in their blood. The technical medical term is that the patients are seropositive. ACPA is both an indicator of rheumatoid arthritis and a treatment target. ANC0031802 binds specifically to ACPA at the inflammation site.

However, the agent does not work on all rheumatoid arthritis patients. In fact, some patients have fairly normal levels of ACPA in their blood, and 15-20 per cent of the patients actually have lower levels—they are seronegative. The drug only has an effect on seropositive patients.

“Our drug candidate only works on approximately 60 per cent of patients with high levels of ACPA. However, these are precisely the patients who experience the worst symptoms, and they’re also those who are today the most difficult to treat,” says Kira Astakhova.

Basic research into biomolecule
Ibio Tech originates from basic research into biomolecules. Kira Astakhova particularly works with advanced strategies for production of nucleic acids, including interactions between nucleic acids, peptides, and antibodies.

It took the research group eight years to arrive at ANC0031802, which consists of a peptide sequence and a nano-particle.

“To enable us to produce the drug, we had to find the optimal peptide sequence for ACPA binding. We then had to add this ACPA-binding peptide to a nanoparticle that could interact with immune cells,” explains Kira Astakhova.

The research group found the peptide sequence based on a combination of literature studies and experiments in which they tested the ability of the sequences to bind to ACPA. They selected the 30 most promising peptide candidates, which were then added to a nanoparticle.

A number of possible nanoparticles were identified, and the five most promising nanoparticles were thoroughly examined for their ability to dissolve in the body, for their size, material properties, immunological properties, and interaction with cells.

Finally, the best candidates for the finished drug were studied in trials with mice and rats.

Other products to fall back on
Due to the rigorous requirements for safety and clinical testing, the time frame for new medicines is significantly longer than for many other types of inventions. Normally, it takes about ten years from the discovery of a new drug candidate and until it is widely used. Ibio Tech has passed the first two years.

ANC0031802 will be ready for the first test on humans in 18 months. If it goes well, the agent must undergo another two studies—in which a much larger number of patients in many countries will receive the drug—until an application can finally be submitted for actual approval of the drug. During the process, the costs will run up to such a high level that a start-up cannot cover the expenses without major investments.

“At some point, we’ll have to either sell the product or enter into a partnership with an existing pharmaceutical company that can shoulder the costs of bringing the product all the way to the market,” says Kira Astakhova. If everything goes as the start-up hopes, this exit—as it is called in entrepreneurial jargon—will take place in about six years. Again, it is a prerequisite that ANC0031802 does not run into obstacles along the way, such as the discovery of unforeseen adverse effects. But even if the product has to be abandoned, this will not necessarily stop the start-up’s activities, says Kira Astakhova:

“What we’ve developed is not only the specific product, but a technology platform that can be used to produce several different related types of medicines. This means that we can develop other candidates relatively quickly. However, both our business plan and the time at which patients can benefit from a new treatment will obviously be postponed.”

Shortcut to early diagnosis
Although ANC0031802 only has an effect on seropositive patients, Kira Astakhova stresses that she is also interested in the other patients who either have normal ACPA levels or are seronegative:

“As a researcher, I want to understand the mechanisms better. It is thought-provoking that the disease manifests itself so differently in different patients,” says Kira Astakhova.

A better understanding of the mechanisms behind rheumatoid arthritis will allow doctors to adjust the treatment so that it is even better geared to the individual patients. At the same time, the hope is also that it can help doctors make the diagnosis at an earlier stage, says Kira Astakhova, and elaborates:

“Early diagnostics will be a great advantage to all treatment types, including the treatment that we will hopefully develop. The earlier rheumatoid arthritis is detected, the greater the chance that we can succeed in treating it and thus give people who otherwise risked disability a good life.”

Read about Kira Astakhova's research and other interesting stories in the latest issue of DTU's Dynamo magazine (Danish)

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