InflaRx Targets Kidney Protection, Steroid Reduction in AAV With Izicopan Trials

Key Points

• InflaRx plans two Phase II trials of oral C5a receptor antagonist izicopan in AAV: a placebo-controlled study focused on renal vasculitis and an open-label study testing rapid corticosteroid tapering and potential discontinuation.
• Kidney involvement affects roughly 70%–80% of AAV patients, while current steroid-heavy treatment carries significant risks. InflaRx believes selectively blocking C5a signaling could protect kidneys while preserving other immune functions.
• The company reported €153.3 million in cash, expects funding through 2029, and estimates izicopan’s global peak AAV sales potential at approximately $1.65 billion, potentially reaching $2 billion with broader use and stronger steroid-reduction data.

InflaRx NASDAQ: IFRX outlined plans to advance its oral C5a receptor antagonist izicopan in ANCA-associated vasculitis (AAV), with an initial focus on patients with kidney involvement and a parallel study intended to evaluate corticosteroid reduction.

During the company’s capital markets event, Chief Executive Officer and Founder Niels Riedemann said InflaRx believes izicopan could offer a differentiated profile based on rapid exposure, potential for tighter C5a receptor control, safety observations to date and a potentially lower pill burden. The company said 197 subjects have received izicopan so far, with no safety signals of concern reported.

AAV Treatment Needs Center on Kidney Protection and Steroid Reduction

Professor Peter Merkel, chief of rheumatology at the University of Pennsylvania, described AAV as a serious and heterogeneous group of small-vessel inflammatory diseases. The presentation focused on granulomatosis with polyangiitis and microscopic polyangiitis, which can affect the upper airways, lungs, nerves and kidneys.

Kidney disease occurs in approximately 70% to 80% of patients, Merkel said, and can lead to renal failure and death. He said physicians need therapies that can more quickly induce remission, protect organs, reduce relapses and limit the need for chronic immunosuppression.

Current treatment still relies heavily on glucocorticoids, or steroids, which can quickly reduce inflammation but are associated with substantial side effects, including infection risk, diabetes, hypertension, bone complications and other conditions. Merkel said infection is the leading cause of death in AAV patients, followed by the disease itself.

Rituximab has become a mainstay of treatment, Merkel said, but many patients require repeat dosing over several years. Patients can relapse even while receiving rituximab, and only about 65% to 70% achieve glucocorticoid-free remission at six months, according to his presentation.

Complement Pathway Rationale

Professor Jörg Köhl of the University of Lübeck reviewed preclinical and translational evidence supporting the role of the complement system, particularly the C5a receptor, in AAV. He said C5a receptor signaling contributes to neutrophil priming and activation, reactive oxygen species release, formation of neutrophil extracellular traps and inflammatory processes that can damage blood vessels and organs.

Köhl cited animal models in which C5- or C5a receptor-deficient mice were protected from kidney injury associated with experimental AAV. He also described transcriptomic evidence showing increased complement-related signaling and C5a receptor expression in kidneys from AAV patients.

According to Köhl, C5a receptor targeting may preserve upstream and downstream complement functions, including portions of the complement system important for responding to infections. He also presented preclinical findings suggesting C5a receptor activity may contribute to the transition from acute kidney injury to chronic kidney disease and fibrosis.

Izicopan Development Strategy

Riedemann said InflaRx plans two Phase II studies in AAV. The first is a randomized, placebo-controlled trial in patients with renal vasculitis. The study will evaluate 30 milligrams twice daily and 60 milligrams twice daily of izicopan against placebo, on top of standardized glucocorticoid tapering in all study arms.

The company expects to enroll about 35 patients per arm, with a key readout at 24 weeks and treatment continuing through 48 weeks. Planned assessments include safety, Birmingham Vasculitis Activity Score remission, estimated glomerular filtration rate, proteinuria and hematuria.

The second Phase II study is an open-label trial enrolling a broader AAV population, including patients without kidney involvement. It is designed to examine whether izicopan can support rapid steroid tapering and potentially complete corticosteroid discontinuation. InflaRx said the study will include an expert safety review at week 16.

Riedemann said the placebo-controlled trial is intended to demonstrate effects on top of standard of care, while the open-label study is designed to assess the potential to reduce or replace corticosteroids.

InflaRx is also pursuing renal opportunities beyond AAV. The company said it expects initial data in atypical hemolytic uremic syndrome, or aHUS, as early as 2027 from an investigator-initiated study. It also plans an open-label basket study in IgA nephropathy and rapidly progressive IgA nephropathy, with initial readouts potentially available in 2028.

Market Research and Financial Position

Chief Financial Officer Tom Taapken said InflaRx commissioned interviews with a dozen rheumatology and nephrology prescribers in the U.S., Europe and Japan. The research found that physicians retained confidence in C5a receptor inhibition as a treatment approach despite issues surrounding another C5a receptor inhibitor, avacopan.

Based on the research and assumptions including pricing comparable to avacopan, Taapken said InflaRx estimated a base-case global peak-sales opportunity for izicopan of approximately $1.65 billion in AAV. The company said the estimate could rise to about $2 billion if izicopan expands into the broader AAV population and generates additional corticosteroid-reduction data.

InflaRx reported a cash balance of €153.3 million and said it expects its cash runway to extend through 2029. Riedemann added that the company retains ownership of izicopan’s intellectual property.

About InflaRx (NASDAQ:IFRX)

InflaRx N.V. NASDAQ: IFRX is a biopharmaceutical company focused on developing therapies for inflammatory and autoimmune diseases. Founded in 2007 and headquartered in Jena, Germany, the company's research is centered on the complement system, an important part of the immune response. InflaRx seeks to selectively block complement component C5a, a potent inflammatory mediator, while preserving other aspects of immune-system function.

The company's lead product, vilobelimab, is a first-in-class monoclonal antibody designed to inhibit C5a.

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