The Covid-19 pandemic created an opportunity for many biotech companies to repurpose their existing programs into vaccines and treatments for the novel coronavirus. Cyxone’s CEO Tara Heitner and COO Malin Berthold discuss how they approached this shift at their company.
Cyxone was founded in 2015 to develop drugs for rheumatoid arthritis and multiple sclerosis. Based in Malmö, Sweden, the company was set up as a virtual startup that worked with CRO partners to run clinical trials. In November 2019, Cyxone’s former CEO resigned. In mid-2020, Tara Heitner took over the position. Shortly after, the company started a program for Covid-19 based on its rheumatoid arthritis drug candidate.
With the help of COO Malin Berthold, who had joined Cyxone in August 2019, Heitner has supervised the growth of the company, which now has six full-time employees. We asked Heitner and Berthold how the global pandemic created an opportunity for biotech companies such as Cyxone and how they handled the changes to test its lead rheumatoid arthritis candidate, rabeximod, as a potential treatment for Covid-19.
When did you realize that your drug candidate could fight Covid-19?
Heitner: I don’t take any credit for this. Shortly after I joined Cyxone, we received a proposal from one of our very close collaborators on the rheumatoid arthritis project, Dr. Kalev Kask, who has worked closely with rabeximod for some time.
Based on his intimate knowledge of rabeximod’s mode of action, Kalev proposed that we should leverage it against Covid-19. In rheumatoid arthritis patients, rabeximod targets a subset of inflammatory immune cells – inflammatory macrophages – that are responsible for the destruction of the joints.
Kalev believed that this subset of immune cells also plays a central role in patients with moderate Covid-19, who have difficulty breathing and get infections. These cells are thought to become overactivated and can cause the cytokine storm that leads to lung dysfunction, the need for oxygen, and, potentially, death. So we had to make a quick decision on whether to leverage rabeximod for Covid-19.
Berthold: We were fortunate because we had many tools already in place allowing us to pivot quickly once the decision was made to set up a rabeximod trial for Covid-19. Rabeximod had already been taken through phase I and phase IIa trials in rheumatoid arthritis patients, so we were all set with the data to go straight into a phase II trial with rabeximod targeting Covid-19. We also had capsules prepared and ready to deploy in a Covid-19 trial.
What were the biggest challenges you faced when starting the Covid-19 program?
Berthold: Most of the documentation was already in place from our rheumatoid arthritis program. We also reached out to the FDA with an investigational new drug application (IND) and asked them to look at our protocol. That is maybe where we lost some time, but on the other hand, we gained quite a lot from the FDA’s valuable feedback on the protocol.
We finally started the trial during Christmas time last year, which was a little bit of a challenge because of holiday times: you have less personnel in hospitals, and patients are a little more reluctant to seek medical care unless they really need to. And since we’re targeting the moderate Covid-19 patients, I think that contributed to the slow start of the trial. Furthermore, in December the pandemic was at its peak which meant that many hospitals were overwhelmed with patients and unable to cope due to being short-staffed.
Heitner: What was challenging was that with this pandemic, the goalposts kept moving. We anticipated starting the trial in the fall, and actually, I believe if we had started in September or October, we would have had an easier time enrolling patients with moderate Covid-19. But by December, we were seeing the absolute peak, where most hospitalized patients had severe forms of Covid-19, and the hospitals were in absolute chaos.
This unpredictability of the pandemic revealed an even greater need for treatments like rabeximod, because we still don’t fully understand when and where the next wave is going to hit which populations at what time of the year. We don’t know how long the vaccines will be effective nor if they will be widely and equitably distributed. So we need to have these types of treatments ready for the future.
Why did you decide to reevaluate your rheumatoid arthritis program while running the new Covid-19 program?
Berthold: We had a lot of data on rabeximod in rheumatoid arthritis patients, which had been generated some time ago by the company that owned the compound before us. When I started at Cyxone, we were planning to set up a second phase II study, which was intended to be a repeat of the first study but with a longer duration, as rabeximod seemed to have a lag phase before its full effect was reached.
But while we were working on the preparations for this second study, Cyxone’s management changed, and with the new management focus on market and competitive analysis, we decided to re-evaluate the trial design in light of an evolving rheumatoid arthritis therapeutic landscape. So we reached out to the researchers who had been working on rabeximod previously and took a detailed look at the data. We realized that the trial design was not up to date with how trials are run nowadays.
In 2020 we also filed five new patents on rabeximod, potentially extending patent protection to 2041. It bought us the time to reconsider the trial design in light of new knowledge which the industry has gained in the past few years. This coincided with the idea to trial rabeximod in Covid-19 patients, so we decided to pause our plans for the phase IIb trial in rheumatoid arthritis patients.
As a small company, it is best to run one trial at a time and not overextend our resources. We are in contact with world-leading experts in targeted study design and targeted therapies, who are looking into which patient population could show the real benefits of rabeximod and we are in the process of finalizing the trial design
We still believe rabeximod is an excellent candidate for rheumatoid arthritis because it has a unique mode of action that can offer patients a safe, tolerable, and easy to take alternative to current therapies. As far as we know, rabeximod is a safe compound with very few side effects, as opposed to what we see in other rheumatoid arthritis drugs. So we believe there is a place for this compound in the field.
Once we have a clearer idea of what patient population to target, we will set up the trial in an appropriate way. Depending on how the pandemic develops – as it is affecting the running of clinical trials – we are hoping to start the trial by the end of this year after the Covid-19 study report is finalized.
How will your program in multiple sclerosis progress given your current focus on Covid-19?
Heitner: We have this very interesting compound called T20K, which is a stable, cyclic peptide that we’re developing for multiple sclerosis based on research originally done at the University of Vienna. The project is currently in the pre-IND stage, but we have limited resources to progress everything in parallel, so right now we are focusing on preclinical development and specifically on evaluating which formulation and form of administration we are going to use.
I think in retrospect we are very lucky that we postponed some of this work because it is a difficult time to operate and run clinical trials. It gives us time to position ourselves properly and to build the team we need to actually run all three programs efficiently.
This year, we are focused on understanding more about the mode of action of our compounds. We will be in a position, probably next year, to look further into clinical development.
How do you plan to approach 2021 and beyond?
Heitner: Right now, our R&D team has a lot on its plate. We are actually preparing for what will happen after the Covid-19 trial – the regulatory path and potential partners to move forward with the program – given a positive readout of our trial later this year.
Although rabeximod is being studied as a treatment for Covid-19, it could also be a treatment for other diseases of the lungs, where the activated or inflammatory macrophage is a key component of the pathology. This is the case for many different viral lung infections, so we see broader market applicability for rabeximod beyond Covid-19 in the future.
We’re also investigating the full regulatory path for the rheumatoid arthritis trial, so we know what we need to do for the phase IIb trial, all the way up to market, and understand what it will take as we start discussions with potential partners for the program.
Our business model is to develop our programs to proof-of-concept and to find co-development or strategic partners to take the programs through late-stage clinical development and to the market.