Reining in Inflammation to Treat ARDS

Acute respiratory distress syndrome (ARDS) is a devastating complication of infection or injury, caused by out-of-control inflammation in the lungs. The COVID-19 pandemic brought the need for ARDS treatment options into sharp focus for many researchers, as doctors have traditionally relied on supportive care rather than targeted therapies to manage this deadly syndrome. At InflaRx, cofounders Niels Riedemann and Renfeng Guo saw an opportunity to intervene directly by targeting the body’s immune response.

Drawing from research on sepsis and complement biology, they developed the monoclonal antibody vilobelimab to block overactive inflammatory responses in patients with severe inflammatory diseases including ARDS.¹ In this Innovation Spotlight, Riedemann discusses the inspiration and mechanisms behind vilobelimab and what the future holds for similar anti-inflammatory therapeutics targeting the complement system.

What is ARDS and what causes it?

ARDS is a life-threatening condition caused by rapid and uncontrolled inflammation in the lung tissue caused by the body’s immune response to different triggers. This leads to breathing difficulties and reduced oxygenation of the blood with reduced oxygen supply to other vital organs with the potential to cause multi-organ failure and death. As ARDS progresses from milder to more severe forms, the lungs themselves no longer function sufficiently, and breathing support, such as invasive mechanical ventilation, is required to keep a person alive.

ARDS can be caused by multiple triggers including viral and bacterial infections in the lung or elsewhere that result in pneumonia or sepsis, and trauma or chemical injury to the lung. COVID-19, which occurs because of SARS-CoV-2 infection, can also cause ARDS.

Prior to the COVID-19 pandemic, how did doctors treat patients who had ARDS?

ARDS is a life-threatening medical condition for which no specific therapies are approved. Treatment of patients with ARDS focuses mainly on supportive care such as organ and systemic support including ventilation, vasopressor treatment, and diuretics, as well as addressing potential underlying causes, for example with antibiotic treatment in case of infections. A significant unmet need remains for new therapies that address the underlying ARDS mechanisms caused by the uncontrolled inflammation due to the body’s immune response to the underlying trigger.

What inspired you to develop ARDS treatments?

Before founding InflaRx, I was a postdoctoral and research fellow at the University of Michigan where I teamed up with Renfeng Guo, the other founder and chief scientific officer of InflaRx. At the University of Michigan, our research was focused on the body’s immune response, including in the devastating setting of sepsis, an immune dysregulating condition.² We found this research so intriguing that we created InflaRx, with a goal of saving people's lives by controlling this immune response.

When the COVID-19 pandemic happened, InflaRx had an extensive store of knowledge on the immune response in life-threatening infections, including in certain viral infections such as the avian flu virus. Targeting the underlying immune dysregulation and hyperinflammation caused by COVID-19 was a logical next step.

What is vilobelimab and how does it work?

Vilobelimab is a monoclonal antibody that targets a protein in the blood called C5a, which is a key factor of our body’s immune response causing strong inflammation. C5a is part of the complement system, our innate fast-acting immune response, which senses disturbances in our system and translates them into an inflammatory reaction. This can lead to the activation of immune cells causing cytokine release and to coagulation disturbances and various other effects. The resulting inflammatory cascade can be so strong that it starts damaging our own tissues and organs. In certain conditions, C5a levels and the associated inflammatory response can be extremely elevated and life threatening, which can be reduced by a C5a blocking drug.

What is next for InflaRx?

InflaRx continues its mission as a pioneering anti-inflammatory therapeutics company targeting the complement system, namely by developing inhibitors of key immune regulators C5a and its receptor C5aR. C5a inhibition with vilobelimab is currently also being investigated in a phase 3 clinical trial for patients with a rare and damaging inflammatory auto-immune skin disease called pyoderma gangrenosum (PG). We are also in phase 2 studies with INF904, an orally available inhibitor of the C5a receptor, which is currently being studied in patients with chronic spontaneous urticaria (CSU) and hidradenitis suppurativa (HS), two conditions in need of new effective oral therapies. Over the second and third quarters of 2025, all three clinical efforts in PG, CSU, and HS are expected to reach clinical milestones.

What excites you the most about the future of inflammatory disease treatment research?

Inflammatory disease drug development is in a renaissance period, with many new mechanisms of action being directed at multiple unmet needs in inflammatory disease. While not all of these approaches will be successful, we believe that the spirit of innovation and determination alive at companies like InflaRx will nonetheless help usher in a new era of drug treatments and better-served patients.