Cyxone recently reached a milestone in its rheumatoid arthritis project, rabeximod, when succeeding in identifying the molecule’s target protein. This means that it is now easier to identify other diseases in which this mechanism of action plays an important role. BioStock reached out to CEO Carl-Magnus Högerkorp for a comment on the company’s year-end report for 2023.

Cyxone develops first-in-class drugs for the treatment of autoimmune diseases. The company’s product portfolio consists of the main candidate rabeximod for the treatment of rheumatoid arthritis (RA) and T20K for the treatment of multiple sclerosis (MS).

Rabeximod is in clinical phase II development and targets patients who do not experience sufficient improvement with today’s disease-modifying antirheumatic drugs (DMARDs), such as TNFα inhibitors.

New findings on rabeximod’s mechanism of action

Recently, Cyxone succeeded in identifying the biological target protein for rabeximod, which was later confirmed in an independent scientific analysis. The new research results provide a more detailed insight into the mechanism of action, i.e. how the candidate affects the pro-inflammatory cells, while confirming its first-in-class status.

In a previous interview with BioStock, CEO Carl-Magnus Högerkorp said that the new knowledge is essential for the further development of the project and that it contributes to an increased understanding of the processes that are affected in the body during treatment. This allows one to design programmes to learn more about the possible side effects of the drug. At the same time, it is important to have a clear picture of the mechanism of action to move forward in partnering discussions. Read the full interview here.

New patient focus for increased commercial potential

On 27 February, Cyxone published the year-end report for 2023, which focuses on the company’s strategy change during the year. A newly appointed Board saw benefits in targeting another patient group that would benefit more from a treatment with rabeximod – patients with inadequate responses to DMARDs, such as TNFα inhibitors.

Today, the intended original group of patients has good access to treatment options. Now the company instead focuses on the patients who do not have these opportunities – which is a much more commercially viable way forward. The new strategy has been developed in consultation with world-leading Key Opinion Leaders in rheumatoid arthritis.

The new strategy involves several smaller, exploratory studies, which is a way for the company to reduce costs. At the end of 2023, the company’s cash and cash equivalents amounted to 17.5 million SEK.

Comments from the CEO

To find out more about the milestones in 2023 and the way forward for Cyxone, BioStock once again reached out to CEO Carl-Magnus Högerkorp.

First of all, can you discuss the new patient population that Cyxone chose to target in 2023?

— As a starting point for the revised strategy, we have looked ahead to understand what the changing landscape looks like for disease-modifying drugs in rheumatoid arthritis. About 25 years ago, biological drugs (TNFa blockers) began to be introduced for the treatment of rheumatoid arthritis. These drugs have since established themselves as a reliable second-line therapy after methotrexate. Due to the success of this type of drug, there followed an intensive period of research and development among the major pharmaceutical companies to develop new biological drugs based on other advances made in immunology in the 1990s. This led to the development of several TNFa blockers, as well as biologics that modulated other pro-inflammatory signalling molecules such as interleukin 1 and interleukin 6.

— This intensive research has meant that patients with rheumatoid arthritis now have access to fairly good treatment options, but which have long been costly. In 2023, the patent protection for one of the most important TNFa blockers, Humira, expired, which led to several pharmaceutical companies choosing to launch their own versions of Humira. The consequence of this is that there are now many good alternatives available that also lead to cheaper treatments.

— However, what we see as the next challenge is the patients who are treated with TNFa blockers but who, for various reasons, gradually stop responding to the treatment. For these patients, there are immediately no good alternatives. It is in this patient group that we see opportunities for rabeximod.

What specific insights from the planning of the original phase IIb study with rabeximod led to the new strategy?

— During the planning of the phase IIb study, which targeted patients who do not respond to methotrexate, we came to realise the great interest in investigating rabeximod in the patient group who have an inadequate response to TNFa blockers. In the planning work, proposals were made to include both patients who do not respond to methotrexate and patients who do not respond to TNFa blockers, since there is a more pronounced medical need in the latter group. With these insights, we chose to contact several different international experts in the field – Key-Opinion Leaders (KOL) – who all agreed that the patient group that does not respond to TNFa blockers does not have good enough treatment options today.

—Our new strategy was therefore based on the feedback we received in this process and allowed us to shape a commercially more sustainable long-term path forward for the project.

You have launched plans that reduce your burn rate, which will be realised through smaller clinical studies, among other things. Are smaller studies enough for you to reach your goals?

— The smaller studies we intend to conduct allow us to increase our knowledge of how rabeximod works more specifically in the diseased tissue. With more detailed knowledge of the mechanism of action and the possibility of identifying biomarkers that can contribute to the development of Companion Diagnostic, these studies will generate several important insights for the continued development of the project. In modern drug development projects, it is very valuable to be able to identify biomarkers that provide increased precision in treatment – precision medicine. With tools that can help determine which patients will benefit most from the treatment, you reduce the risk of unnecessary and ineffective treatment, something that is rewarded in today’s healthcare system.

What is the strategy for securing clinical collaborations with KOL and successful studies with rabeximod?

— With the new strategy for rabeximod, we intended to conduct smaller clinical studies together with academic centres and the KOLs associated with them. Since last summer, we have continued our dialogue with the KOLs we have established contacts with and have actively worked with these groups on the design of the studies, protocols and budgets. We are strengthened by the great and active interest we see from these research groups about rabeximod’s mechanism of action and how well it fits into their own research interests. This means that we can work with very well-known researchers in the field.

In the report for 2023, you also emphasise that your second candidate, T20K, as a drug concept is attracting great global interest among researchers who are active in the field of cyclotides. Would you like to elaborate on this?

— During the year, there have been very promising scientific publications on ways to produce cyclotides through plant-based production. As the prototype cyclotide, the research team made the choice to use T20K. Thus, in the long run, their learnings will be able to be translated into a simple and scalable plant-based manufacturing process for T20K. Cyclotides have proven to be a bit of a challenge to produce through plant-based production, but this research group has now smartly addressed these challenges, and we are therefore following their research with excitement.

—The T20K project is also attracting interest based on its biological mechanism of action. T20K and the combination with Kappa-opioid receptor (KOR) agonism is an area that is being looked at more and more as an interesting possibility to slow the progression of multiple sclerosis. In preclinical studies, we have seen promising synergistic effects with T20K in combination with KOR agonism. Several scientific articles have recently taken a closer look at this concept and also made note of what we do in Cyxone. Of course, we need to learn more about this mechanism and build more preclinical evidence before we can invest in clinical programmes.

With the in-depth knowledge of rabeximod’s mechanism of action, you not only reduce the risks in the project – you can now also start looking at new indications where the same mechanism can be beneficial. Do you already see any such potential areas?

— The new insights we have about the target protein for rabeximod mean that we see several interesting possibilities with the molecule. Within the autoimmune/autoinflammatory spectrum, there are more than 150 indications, where macrophages often have a significant role in the underlying aetiology (cause of the disease). Most of these diseases today have few good treatment options and are often treated with cortisone or other simpler non-selective anti-inflammatory drugs. There is a great unmet medical need where new innovative, more effective and safe drugs are needed.

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