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InflaRx presents new preclinical findings for INF904

InflaRx announced the presentation of preclinical data for the company’s novel oral C5aR inhibitor, INF904, at the 2024 European Meeting on Complement in Human Diseases (EMCHD 2024) being held in Lubeck, Germany, September 2 – 6, 2024.

Members of InflaRx leadership also participated in a satellite symposium highlighting the role of the C5a/C5aR1 axis in driving inflammation and served as the biopharma industry representative on a panel focused on the relevance of targeting C3 and C5. InflaRx also hosted a lunch seminar focused on C5a/C5aR inhibition in human disease with best-in-class compounds.

Preclinical pharmacological characterization of INF904, an oral small molecule antagonist to complement 5a receptor: Overall, this study demonstrated that INF904 is a highly selective and potent inhibitor of C5aR1 with promising pharmacokinetic properties, while also exhibiting strong efficacy potential in vivo. Both INF904 and avacopan were evaluated through a series of cell-based, ex vivo, and in vivo assays. In a hamster neutropenia model, INF904 inhibited C5a-induced neutropenia by 96.5% compared to 51.1% for the same dose of avacopan. INF904 also demonstrated a more favorable PK profile with 2- to 5-fold higher exposure than avacopan across all tested animal species.

The data also indicated that INF904 is a much weaker inhibitor of CYP3A4/5, with an IC50 value of 62 microM, compared to 1.7 microM for avacopan. CYP3A4/5 enzymes play an important role in the metabolism of a variety of drugs, including glucocorticoids. INF904, a novel oral C5a receptor 1 antagonist, shows promising therapeutic effects in inflammatory disease models: Results from in vitro and in vivo inflammatory disease models indicated that INF904 acts by reducing neutrophil activation.

In two in vitro whole blood disease models, INF904 effectively blocked CD11b upregulation on neutrophils in a dose-dependent manner. Further, in three hamster models used to assess INF904’s therapeutic effects after oral dosing, significant anti-inflammatory effects were noted, including reduced influx of neutrophils, significant reductions in plasma levels of CREA and BUN, and histological improvements.

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