InflaRx (NASDAQ:IFRX) highlighted recent clinical updates and strategic priorities for its complement inhibition platform during a presentation at Oppenheimer’s 36th Annual Healthcare Life Sciences Conference. CEO Niels C. Riedemann said the company has recently streamlined its corporate strategy toward advancing its oral C5a receptor 1 (C5aR1) inhibitor, izicopan, across inflammatory and immunology (I&I) indications, while continuing to advance vilobelimab, an intravenous anti-C5a antibody, in acute respiratory distress syndrome (ARDS).
Focus on terminal complement inhibition and why C5a/C5aR
Riedemann outlined the company’s focus on the “terminal complement pathway,” targeting either the C5a ligand or its receptor. He described C5a/C5aR signaling as a key translator of inflammatory “danger signals” into innate immune cell activation, particularly involving neutrophils, macrophages, and monocytes, which can contribute to tissue damage during inflammatory flares.
Izicopan: reported differentiation vs. marketed comparator
InflaRx presented its view that izicopan may be differentiated from avacopan, a marketed C5aR inhibitor used in ANCA-associated vasculitis. Riedemann emphasized that comparisons shown were not head-to-head in humans, but he cited several areas where the company believes izicopan is differentiated:
- Pharmacokinetics (PK) and exposure: He said izicopan showed substantially higher exposure in reported comparisons, including a “10x increase” in area under the curve and “3x higher peak,” and noted that dosing was tested safely up to 240 mg.
- Target engagement: InflaRx showed data indicating 90%–100% inhibitory potential at doses above 30 mg, while stating that reported avacopan data reached roughly 50% blocking activity.
- Speed to therapeutic levels: Riedemann said izicopan reached therapeutic exposures quickly (including “already on day 1”), while citing that avacopan takes substantially longer to reach steady state in ANCA-associated vasculitis.
- Drug-drug interaction and safety considerations: He said izicopan had “36-fold less engagement” with CYP3A4/5 inhibition than avacopan, which he argued could be important for avoiding liver-related safety signals. He added that InflaRx has not observed safety concerns so far in “over 80” human subjects dosed for up to four weeks.
- Formulation and dosing convenience: He noted izicopan’s 30 mg dose can be delivered in one capsule and suggested potential for up-dosing and possible once-daily dosing in the future.
Riedemann also referenced an in vivo hamster experiment described as a head-to-head comparison with avacopan, stating izicopan showed higher plasma presence and nearly doubled inhibitory potential in plasma at the same dose, while noting that the two compounds have similar in vitro IC50 values.
Phase II hidradenitis suppurativa (HS): lesion, tunnel, and pain signals
InflaRx discussed results from a four-week, open-label phase II study of izicopan in hidradenitis suppurativa. Riedemann said 29 patients were evaluable at the time of the reported analysis, with a follow-up assessment at week eight in 25 patients after four weeks off treatment. Dosing cohorts included 60 mg twice daily, 90 mg twice daily, and 120 mg twice daily. He noted two additional patients in lower-dose groups were not included in the analysis at the time and would be presented later.
Riedemann described HS as a debilitating disease with painful inflammatory nodules and abscesses, and chronic “draining tunnels” that can significantly affect quality of life. He linked the C5aR pathway to neutrophil recruitment and NETosis, which he said has been described as a driver of tunnel formation.
Key efficacy observations discussed included:
- Abscess and inflammatory nodule (AN) count: Riedemann said AN counts improved as early as week one across doses, with the most prominent reduction in the 120 mg cohort, which he characterized as having higher baseline disease burden.
- Draining tunnels: He reported reductions in draining tunnels across all three dose groups, again described as strongest in the 120 mg cohort. He also said 50% of patients in the high-dose group had zero tunnels at week four, with the overall average close to 30%.
- HiSCR (clinical response endpoint): He reported a 38% HiSCR in the high-dose cohort at week four and an average around 28%. After treatment stopped, he said responses continued to deepen by week eight, with the high-dose cohort at 63% and the overall average at 44%.
- Pain: Riedemann highlighted pain improvement as a key differentiator, stating that by week four, up to 75% of patients (and 66% on average) achieved NRS30 (a 30% improvement in pain and at least a two-point reduction on a 0–10 scale). He tied the pain benefit to early improvements in abscesses and draining tunnels.
He also said drug levels remained measurable at week eight and described them as still providing significant pathway blocking. Riedemann added that the company observed no safety signals of concern in the study.
Chronic spontaneous urticaria (CSU) and other development considerations
InflaRx also summarized a small phase II study in chronic spontaneous urticaria, in which approximately 30 patients received izicopan at 60 mg or 120 mg. Riedemann cited a rationale tied to C5a-driven histamine release from mast cells and basophils, as well as evolving evidence on neutrophils in more severe disease. He noted that despite available therapies such as antihistamines and anti-IgE drugs, a portion of patients remain symptomatic.
In the CSU dataset, he said the company observed a meaningful reduction in Urticaria Activity Score 7 (UAS7) by week four, including overall reductions of about 15 points and up to 18.7 points in a more severe subgroup (baseline UAS7 of 28 or higher). He also referenced a subgroup with concomitant angioedema that showed a “remarkable response,” including on angioedema-related measures, though those data were not shown on the slide discussed.
Riedemann said HS is currently the company’s top priority for izicopan development, while CSU is viewed as a potential opportunity for a “safe oral drug” but not at the highest priority level.
ANCA-associated vasculitis: assessment underway
During Q&A, Riedemann said InflaRx is “deeply assessing” potential development in ANCA-associated vasculitis and sees a commercial opportunity, citing reported global sales of the marketed comparator and suggesting the market could exceed $1 billion. He argued izicopan could potentially support a differentiated label, including around corticosteroid-sparing, based on the company’s view that reduced CYP3A4/5 interaction could avoid confounding steroid exposure levels.
He also referenced prior work in the indication with the company’s antibody approach and noted that a partner in China is conducting a phase III program using the mechanism, which he said supports validation of C5a/C5aR inhibition in the disease area.
InflaRx said it is in active discussions with the FDA regarding HS development and expects to provide additional updates around a planned Capital Markets Day in the spring. The company also stated it is cash-funded into mid-2027.
About InflaRx (NASDAQ:IFRX)
InflaRx N.V. is a clinical‐stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapies targeting the complement system, with an emphasis on the complement‐1a (C5a) pathway. The company’s lead product candidate, vilobelimab (IFX‐1), is a monoclonal antibody designed to selectively inhibit C5a, a potent pro‐inflammatory peptide implicated in a range of autoimmune and inflammatory diseases. InflaRx seeks to address high‐unmet medical needs by advancing treatments for conditions such as hidradenitis suppurativa, pyoderma gangrenosum and other rare and severe inflammatory disorders.
Vilobelimab has been evaluated in multiple Phase II trials, demonstrating proof of concept in reducing key inflammatory markers and improving clinical outcomes.
