InflaRx announces INF904 development plans

InflaRx has chosen two initial immuno-dermatology indications that it intends to pursue with INF904 via the initiation of a Phase IIa “basket study”. These indications initially include CSU and HS, two chronic inflammatory skin conditions in which C5a has been suggested to play a significant role and where a high unmet need exists. In addition, with INF904 being an oral drug with a mechanism of action currently not addressed by other drugs in development for these indications, the company sees a unique opportunity to improve standard of care for patients with these conditions. InflaRx estimates significant market potential for INF904 in these two indications, both estimated as multi-billion-dollar markets. InflaRx is currently conducting additional pre-clinical studies, including chronic toxicology studies, to enable longer-term dosing of INF904. Consistent with previous communications, InflaRx anticipates initiating a Phase IIa study with INF904 before the end of 2024. This open-label Phase IIa study is expected to explore at least three different doses of INF904 for a duration of 4 weeks and to assess pharmacokinetic and pharmacodynamic parameters in patients, as well as provide safety data and certain early efficacy readouts. Data from this Phase IIa study is expected to be released in 2025. InflaRx expects to initiate a larger and longer-term Phase IIb study in 2025 as well. INF904 for CSU CSU is a debilitating and unpredictable skin disease characterized by intensely itchy hives / wheals and angioedema. The burden of this chronic disease is high and impacts sleep, mental health, quality of life and productivity due to absences from school and work. CSU is estimated to affect around 40 million people worldwide. CSU patients have been reported to show elevated C5a levels, a major activator of mast cells and basophils, which are thought to be significant contributors to CSU pathogenesis. In addition, studies suggest that complement activation (including C5a) in CSU can lead to histamine release. Current treatments are limited, and a significant unmet need exists in a sizable proportion of patients. As an orally available agent with a favorable PK / PD profile that could drive a broad dose range for systemic exposure, INF904 could find a differentiated position in the CSU market. INF904 for HS HS is a chronic, recurrent, debilitating neutrophil-driven inflammatory disease that can persist for years and tremendously impacts quality of life; it is characterized by abscesses, nodules and draining tunnels which can flare and cause scarring. INF904 inhibits the known C5a-induced effects on neutrophil activation and tissue accumulation of immune cells, including generation of tissue damaging mechanisms (enzyme release and oxidative radical formation) as well as induction of NETosis – mechanisms thought to be involved in HS progression and draining tunnel formation. Clinical evidence with existing C5a/C5aR products also supports that blocking this pathway reduces lesion counts. Patients’ responses to treatment with approved anti-TNF-alpha or anti-IL17 drugs are known to wane over time in a significant number of cases, and treatments with new mechanisms are needed for these patients. As an orally available agent with a favorable PK / PD profile that could drive a broad dose range for systemic exposure, INF904 could find a differentiated and commercially advantageous place in HS treatment. INF904 as a “pipeline-in-a-product” Given the potential of INF904 to have a broad commercial footprint, InflaRx believes it could address meaningful markets in immuno-dermatology and in immuno-inflammation, including in neurology, nephrology and hematology. While InflaRx intends to focus its resources on its immediate goals with CSU and HS, it also assesses pursuit of these additional areas via potential future collaborations with partners. Immuno-dermatology pipeline focus: Vilobelimab for PG InflaRx’s strategy and planning for vilobelimab in PG remain unchanged and its development is currently on track. InflaRx is conducting a multi-national, randomized, double-blind, placebo-controlled pivotal Phase III study with vilobelimab for the treatment of ulcerative PG, a rare, chronic inflammatory form of neutrophilic dermatosis characterized by accumulation of neutrophils in the affected skin areas. The trial study has two arms: vilobelimab plus a low dose of corticosteroids and placebo plus the same low dose of corticosteroids. The primary endpoint of the study is complete closure of the target ulcer at any time up to 26 weeks after initiation of treatment. The study has an adaptive design with an interim analysis blinded for the sponsor and investigators planned upon enrollment of approximately 30 patients. Depending on the results of the interim analysis, the trial sample size will be adapted, or the trial will be terminated due to futility. The enrollment period is projected to be at least two years, depending on the total trial size after sample size adaptation. Vilobelimab has been granted orphan drug designation for the treatment of PG by both the U.S. Food and Drug Administration in the United States and the European Medicines Agency in Europe, as well as fast track designation by the FDA.