Oral C5aR Inhibitor INF904 Shows Early Efficacy in HS and CSU Phase 2a Trials

Today, InflaRx reported topline results from its phase 2a clinical study of INF904, an orally administered, small-molecule C5a receptor (C5aR) antagonist being investigated for the treatment of hidradenitis suppurativa (HS) and chronic spontaneous urticaria (CSU). These preliminary data suggest early signals of efficacy across both indications, alongside a favorable safety profile, supporting further clinical development of this complement pathway inhibitor.¹

Hidradenitis Suppurativa: Study Design and Key Findings

The HS phase 2a trial (NCT06555328) enrolled 29 evaluable patients across 3 dosing cohorts, INF904 60 mg, 90 mg, and 120 mg twice daily (BID), for 4 weeks of treatment followed by a 4-week observation period. Primary endpoints included safety and pharmacokinetics, while exploratory measures assessed changes in inflammatory lesion counts (abscesses and nodules [AN]), draining tunnels (dT), HiSCR (Hidradenitis Suppurativa Clinical Response), pain (NRS), and quality of life (DLQI).

Efficacy Signals

By week 4, researchers found INF904 treatment led to meaningful reductions in AN count across all dose groups. The highest dose (120 mg BID) showed an average decrease of 8.1 AN lesions, a reduction magnitude comparable to biologics in successful phase 3 programs such as adalimumab (Humira; AbbVie) and secukinumab (Cosentyx; Novartis) at similar timepoints.

Reductions in draining tunnels were observed in up to 50% of patients at week 4, according to researchers, again aligning with benchmarks from approved biologic therapies. Composite inflammatory burden (ANdT) and IHS4 scores declined in parallel, suggesting a broad anti-inflammatory effect.

Clinical response rates, measured by HiSCR50, increased progressively through treatment and follow-up, with pooled HiSCR50 rates reaching approximately 44% at week 4 and 63% at week 8, indicating sustained benefit after drug discontinuation. Improvements in pain (NRS30) were reported in about 65% of patients at week 4, while DLQI scores improved by a mean of 5–10 points, reflecting tangible patient-reported benefit.

Safety

No serious adverse events (SAEs) or safety signals were detected in the HS cohort. Three mild (grade 1) adverse events were considered possibly or likely related to treatment. There were no laboratory abnormalities or discontinuations attributed to INF904.

Chronic Spontaneous Urticaria: Study Design and Outcomes

The CSU phase 2a portion (NCT06555328) included 30 evaluable patients, randomized to INF904 60 mg or 120 mg BID for four weeks, followed by 4 weeks of observation. The trial included both anti-IgE–naïve and anti-IgE–experienced patients, representing a clinically relevant spectrum of disease refractoriness. Efficacy endpoints included UAS7 (Urticaria Activity Score) and UCT7 (Urticaria Control Test), alongside safety and pharmacokinetic (PK) assessments.

Disease Activity and Control

At week 4, INF904 reduced mean UAS7 scores by –13.7 points in the 60 mg group and –7.9 points in the 120 mg group, with reductions persisting through week 8. These values fall within the range observed for agents such as omalizumab (Xolair; Novartis), remibrutinib (Rhapsido; Novartis), and dupilumab (Dupixent; Sanofi/Regeneron) in their phase 2 and 3 programs. Patients with severe baseline disease (UAS7 ≥28) showed even greater improvement (–15.4), and those with concurrent angioedema demonstrated the most pronounced reduction (–18.7).

Notably, UAS7 improvement extended to patients with low baseline IgE levels (<40 IU/L)—a subgroup representing the Type IIb autoimmune CSU phenotype—suggesting activity across immunopathologic subsets. Corresponding improvements in disease control were reflected in UCT7 scores, which researchers stated increased by over 4 points on average, with roughly 30% of patients achieving UCT7 ≥12 (“well controlled”).

Safety

As in the HS cohort, INF904 was well tolerated in CSU patients. No serious or severe treatment-related adverse events occurred. One mild (grade 1) AE was deemed possibly related to study drug. Overall safety data were consistent with prior phase 1 findings.²

Clinical Perspective and Next Steps

For clinicians managing HS and CSU, 2 chronic, relapsing inflammatory skin disorders with substantial unmet need, the INF904 topline results are noteworthy. Across both conditions, researchers found INF904 demonstrated rapid onset, biologic-like efficacy, and oral convenience, without emerging safety concerns. Particularly intriguing are the early signals in CSU subgroups poorly responsive to anti-IgE therapy and the consistent impact on draining tunnels and pain in HS.

As these are topline, preliminary findings, final validated analyses and longer-term data are awaited. Nonetheless, the absence of significant safety findings and the early depth of clinical response support advancement of INF904 into larger, controlled trials. For clinicians, these data highlight the evolving potential of complement pathway modulation as a therapeutic avenue in dermatologic inflammation.

Mechanism of Action and Rationale

INF904 targets the C5a/C5aR axis, a key driver of neutrophil activation and downstream inflammatory cascades. Unlike monoclonal antibodies that neutralize circulating C5a, INF904 inhibits its receptor (C5aR1) directly on immune and tissue cells. This mechanism theoretically allows more sustained control of complement-driven inflammation at the site of disease activity. As a small-molecule oral compound, INF904 is also designed for efficient tissue penetration and convenient dosing compared to parenteral biologics.

In preclinical and phase 1 studies, INF904 demonstrated a rapid onset of C5aR blockade, achieving >90% inhibition of C5a-induced signaling and approximately 3-fold higher peak exposure compared to avacopan, a marketed C5aR antagonist.² Phase 2a PK data indicated steady-state plasma concentrations within the first week of dosing.

References

1. InflaRx reports positive phase 2a data for INF904 in hidradenitis suppurativa (HS) and chronic spontaneous urticaria (CSU). News release. InflaRx. Published November 10, 2025. Accessed November 10, 2025. https://www.inflarx.de/Home/Investors/Press-Releases/11-2025-InflaRx-Reports-Positive-Phase-2a-Data-for-INF904-in-Hidradenitis-Suppurative--HS--and-Chronic-Spontaneous-Urticaria--CSU-.html
2. InflaRx announces positive topline results from the single ascending dose (SAD) phase I study with C5aR inhibitor INF904. News release. InflaRx. Published September 11, 2023. Accessed November 10, 2025. https://www.inflarx.de/Home/Investors/Press-Releases/Press-Release~2023-09-InflaRx-Announces-Positive-Topline-Results-from-the-Single-Ascending-Dose--SAD--Phase-I-Study-with-C5aR-Inhibitor-INF904~.html