INF904 Demonstrates Biologic-Like Efficacy in HS and CSU

In a recent interview with Dermatology Times, Camilla Chong, MD, chief medical officer at InflaRx, outlined the evolving clinical promise of complement C5a receptor inhibition in dermatologic disease, particularly hidradenitis suppurativa (HS) and chronic spontaneous urticaria (CSU). Chong, whose background spans cardiology, respiratory medicine, immunology and dermatology, framed the development of InflaRx’s oral small-molecule C5aR inhibitor (INF904) within a broader immunologic paradigm.

Although trained in cardiology, her shift toward immune-mediated disease has shaped her perspective on dermatology drug development. “Immunology is the fundamental of so many diseases… it drives everything,” she emphasized—a useful lens when examining C5a-driven neutrophilic inflammation in HS and subsets of CSU.

Early Clinical Signal in HS

INF904’s most striking early data come from its phase 1/2 HS PK-safety study. While the study design emphasized safety, the magnitude of early efficacy at just 4 weeks has generated significant interest.^1-2

Across 3 doses, 60 mg, 90 mg, and 120 mg, investigators observed reduction across all major lesion domains, with apparent continued improvement even after dosing stopped at week 4 and patients were followed through week 8. \Chong explained: “If you look across those 3 doses, at week 4, we achieve just under 30% (HiSCR50) but from week 4 to week 8, the efficacy continues up to 40%.”

For HS, where deep, painful draining tunnels often drive morbidity, early improvement in pain was particularly meaningful. She highlighted the patient-reported impact: “Patients actually feel a tremendous reduction in their pain… when patients have relief from their draining tunnels, it's no surprise that the pain goes.”

This rapid reduction in NRS skin pain, including both ≥30% and ≥2-point improvements, suggests that C5aR inhibition may modulate not only inflammatory lesion burden but also the nociceptive consequences of chronic tunnel formation.

CSU: Early Onset and Potential Endotypic Clues

In CSU, the 60 mg dose produced consistent reductions in UAS7 comparable to activity thresholds seen in other early-phase targeted therapies. The 120 mg signal was less linear, but the small dataset suggested potential differential responsiveness among patients with low IgE or prior IgE-targeted therapy exposure.

Chong proposed that complement-driven neutrophilic inflammation may represent a parallel or complementary mechanism to mast cell activation: “There's the inflammatory milieu that you then need to actually work on. These things are already ongoing, so it will take a little bit of time, but with time, you see that deepening of effect.”

The continued improvement between weeks 4 and 8 in CSU mirrored the HS findings and supports ongoing exploration into appropriate dosing schedules and candidate endotypes for maximal benefit.

Differentiation From IL-17 Blockade in HS

The current HS therapeutic landscape is dominated by TNF-α and IL-17 inhibitors. While efficacious, these agents leave a substantial proportion of patients with persistent draining tunnels and pain. Chong noted this mechanistic gap: “You’re blocking one mechanism… we know that HS is more heterogeneous than that… you need to block C5a.”

Neutrophil-rich tunnels may be particularly suited to C5aR blockade, and an oral small molecule may offer improved tissue penetration compared with biologic antibodies.

Positioning an Oral Agent With Biologic-Level Efficacy

An oral therapy with biologic-like efficacy presents a disruptive therapeutic option. For patients who prefer to avoid injections, or who have cycled through multiple IL-17 inhibitors, an oral C5aR inhibitor could shift treatment sequencing.

Although Chong stressed that initial positioning would be pragmatic rather than first-line, she emphasized potential long-term evolution: “There is no reason why in the future, INF904 should not be positioned as a first-line treatment.”

Next Steps

InflaRx plans to prioritize HS development given the magnitude of unmet need, while continuing strategic exploration in CSU and potentially other neutrophilic dermatoses. Future trials will refine dose selection, evaluate longer-term efficacy, and further characterize relevant patient subgroups.

For clinicians treating HS, especially those managing patients with refractory draining tunnels, the emergence of a fast-acting, oral, complement-targeted mechanism may signal a meaningful expansion of therapeutic choice. As Chong summarized in closing, “What I would really like patients to have is choices, so you get what is right for you, not just because it’s the only thing that’s available.”

References

1. 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 24, 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

2. 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 24, 2025. https://www.biospace.com/press-releases/inflarx-reports-positive-phase-2a-data-for-inf904-in-hidradenitis-suppurative-hs-and-chronic-spontaneous-urticaria-csu