IFRX News & Events

InflaRx announced that it intends to develop izicopan, an oral C5a receptor inhibitor, in AAV, a life-threatening kidney disorder. InflaRx is conducting Phase 2 planning for izicopan in AAV and is evaluating the feasibility of multiple development approaches, including the potential for an expedited path to the commercial market, in an effort to best address the evolving regulatory environment surrounding the currently approved comparator, avacopan. In addition, the company has announced its goal of establishing rapid proof of concept for izicopan across a broader range of complement-mediated life-threatening kidney diseases by conducting open-label studies that are expected to begin generating clinical data next year in certain indications. Toward these efforts, InflaRx anticipates conducting a pharmacokinetic bridging study in China this year.

InflaRx announced new pre-clinical data demonstrating low reactive metabolite formation of izicopan in human liver microsomes. Reactive metabolite formation is widely used in drug development as an early mechanistic indicator of potential bioactivation-related safety risk. Izicopan is an investigational oral C5aR1 inhibitor designed to achieve differentiated pharmacological properties. In a head-to-head in vitro study using a standard glutathione trapping assay in human liver microsomes, izicopan demonstrated minimal reactive metabolite formation, with conjugate remaining low throughout the incubation period. These findings support a low level of bioactivation in this assay system. Under the same experimental conditions, avacopan showed higher levels of thiol adducts, including both glutathione and downstream cysteine conjugates, consistent with more extensive oxidative bioactivation. Differences in total reactive conjugate peak areas were most pronounced at early time points and remained observable over the course of the assay. Overall, these results suggest a lower extent of reactive intermediate formation for izicopan in this experimental setting. While in vitro findings do not directly predict clinical outcomes, InflaRx believes these results support the differentiated profile of izicopan.

InflaRx announced new in vitro findings demonstrating that izicopan does not exhibit time-dependent inhibition of CYP3A4, an important indicator for the risk for drug-drug interactions and liver toxicity. These results further support izicopan's potential as a differentiated, oral C5a receptor inhibitor. To build upon previous CYP interaction data for izicopan, which showed only marginal inhibition of CYP3A4 in a time-dependent inhibition IC50 shift assay, InflaRx conducted a mechanistically informative Ki-based TDI study. While TDI shift assays serve as rapid screening tools to identify potential time-dependent inhibition, Ki/Kinact studies provide a more definitive and quantitative assessment, enabling a reliable determination of the presence or absence of time-dependent inhibition. The Ki-based TDI study confirms that izicopan does not inhibit CYP3A4 and exhibits no time-dependent inhibition up to the highest tested concentration, supporting a low risk of clinically relevant DDIs. Using two probe substrates, midazolam and testosterone, no evidence of CYP3A4 time-dependent inhibition was observed, providing mechanistic confirmation of izicopan's favorable pharmacological profile. This feature is particularly important, as time-dependent CYP3A4 inhibition can result in DDIs, hepatotoxicity, or reduced metabolism of concomitant medications such as corticosteroids.