InflaRx N.V. is a clinical-stage biopharmaceutical company focused on developing anti-inflammatory therapies by targeting the complement system, specifically C5a, to treat severe immune-mediated diseases.
Niels, how does a bike mechanic end up as the CEO of a successful biotech company?
While my background as a bike mechanic might not seem directly relevant, one thing I learned from that experience is to never accept "no" as a final answer and always look for solutions. From an early age, I wanted to become a doctor, which I eventually did, becoming a board-certified general surgeon and intensivist. However, during my journey, I took a detour into research and went to the University of Michigan in Ann Arbor. That is where I met my co-founder, Prof. Renfeng, who was then a Chinese postdoc and is now an American scientist. We worked together in the renowned lab of Dr. Peter Ward, focusing on the complement system, particularly C5a, and its receptor.
One night, we were so intrigued by our findings that we began discussing founding a company to develop therapies based on our discoveries. We were part of a larger discovery team in that lab, working on life-threatening inflammation, particularly sepsis and lung injury. Our goal was ambitious—we wanted to develop a drug that could help septic patients survive. Despite the pharmaceutical industry’s repeated failures in developing effective sepsis treatments, we believed we had the right mechanism and insights into important key metrics. To deepen my understanding, I spent over six years leading an ICU, participating in trials to learn firsthand why previous drug attempts may have failed. Eventually, in 2015, I left my academic role to focus fully on taking our company public on Nasdaq, which we successfully did in the year 2017.
Your biggest success so far has been vilobelimab – it has gotten some important approvals in the US and the EU recently…
I want to clarify that vilobelimab is not fully approved in the U.S.—it has only received emergency use authorization for certain critically ill COVID-19 patients requiring invasive mechanical ventilation or lung replacement therapy. In the EU, however, it has been granted an exceptional circumstance approval for certain patients with SARS-CoV-2 induced moderate to severe ARDS (acute respiratory distress syndrome).
Understood. Is ARDS the same as what became popular during the pandemic as ‘cytokine storm’?
COVID-19 disease progresses through different stages. Initially, patients experience flu-like symptoms, which can range from mild to severe. Most people recover, but in some cases, an exaggerated immune response kicks in, leading to severe inflammation and compromising the lung function with respiratory distress.
The complement system plays a significant role in this immune overreaction. Studies have shown that levels of C5a, the target of our drug, strongly correlate with disease severity. As the disease progresses, patients may require oxygen therapy, invasive mechanical ventilation, or even extracorporeal membrane oxygenation (ECMO). At this stage, both cytokines and the complement system become highly elevated, contributing to tissue damage. The complement system acts upstream of cytokines—it detects pathogens and signals our body´s immune cells to respond to them. However, when this response is excessive, it leads to tissue destruction, similar to what happens in autoimmune diseases but more acute and ferocious. Our drug targets this overactivation, addressing the immune response rather than the virus itself, which is why we believe it has shown promise in these very severe COVID-19 cases.
What results have you observed when vilobelimab is administered?
Our Phase 3 trial enrolled critically ill COVID-19 patients who required invasive mechanical ventilation or ECMO. This was a randomized, placebo-controlled study, and we demonstrated a 23.9% relative reduction in all-cause mortality at day 28 on top of standard of care. That is a significant result, especially considering how difficult it is to improve survival rates in patients who are already experiencing severe organ failure. The trial's endpoint, all-cause mortality reduction at day 28, is a widely accepted measure in life-threatening conditions like sepsis.
That being said, efficacy is only one side of the equation. Safety is equally important, and I always encourage people to review the published data, including the safety profile which is detailed on the fact sheet, which is available on regulatory and company websites. Balancing risk and benefit is critical in any drug regulatory authorization process, and we want to ensure that all the required and necessary information is available to make informed decisions.
You initially founded the company with the goal of treating sepsis, yet you put that effort on hold. Was that due to funding challenges?
Yes. When we initially pursued sepsis treatment, we realized that neither investors nor pharmaceutical companies were willing to fund large-scale Phase 3 trials due to the industry's history of repeated failures in this area. Conducting these trials is incredibly expensive and high-risk. The consensus at the time seemed to be that sepsis was simply too complex to treat effectively with a single drug, and many companies back then abandoned their efforts after multiple failed attempts.
However, the mechanism we target—C5a—has not just been studied in models of sepsis. Sepsis, by definition, involves both an infection and an immune response that leads to organ dysfunction. Our approach addresses the inflammatory response, which is present and thought to be relevant to multiple diseases. That is why we pivoted with our development efforts to other inflammatory conditions. We have a key development focus on inflammatory immuno-dermatological indications where we see also a high unmet medical need for patients. We are currently conducting studies in this field in different diseases with two different drugs including vilobelimab.
Do you plan to return to sepsis research if your current efforts prove successful?
We have always believed that sepsis remains an area where our approach could make a difference. However, it is important to emphasize that any return to broader sepsis research would require extensive additional studies. Just because we have demonstrated efficacy in COVID-19 disease does not mean we can automatically assume that we can demonstrate the same for other areas like broader sepsis—it has to be thoroughly investigated through well-designed clinical trials.
That said, our work in COVID-19 has provided valuable proof that targeting the immune response in a septic-like condition can be beneficial. This knowledge will likely drive further research into broader ARDS settings, and possibly sepsis itself in the future. If we had unlimited resources, we would probably start additional studies in these settings immediately, but for now, we have a clearly defined focus in a different medical field.
Your research also extends into dermatology…
Yes, our entry into immuno-dermatology was driven by the hypothesis that C5a could play a crucial role in neutrophilic skin diseases, a category of skin diseases where neutrophils drive inflammation. Two diseases we are particularly focused on are hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG). These conditions involve excessive neutrophil activation, and since C5a is a key driver of neutrophil movement and activity, blocking it may help reduce inflammation and tissue damage.
We are currently conducting a Phase 3 trial for vilobelimab in PG and have also developed INF904, an oral C5a receptor inhibitor, which we believe has best-in-class potential. We are testing this new molecule in HS and are also exploring its use in chronic spontaneous urticaria, an allergic skin condition. The original name for C5a was "anaphylatoxin," highlighting its role in allergic reactions, so we believe this research could open new avenues for treating allergic and inflammatory diseases beyond dermatology.
How would you compare the biotech investment climate in the U.S. and the EU?
Our primary focus remains on the U.S. market and investors, as our key shareholders are based there, and Nasdaq provides the most dynamic environment for biotech financing. The U.S. investment landscape tends to be more risk-tolerant, particularly in innovative fields. However, we are seeing increasing interest from European investors, particularly as our research progresses.
That said, our company operates in both regions, US and Europe—and we do have German and U.S. company sites and entities and a growing presence in both territories.
