InflaRx N.V. (NASDAQ: IFRX) announced pre-clinical data showing izicopan demonstrated minimal reactive metabolite formation in human liver microsomes compared to avacopan, a marketed C5aR1 inhibitor.

In a head-to-head study using glutathione trapping assay in human liver microsomes, izicopan showed low conjugate levels throughout a 40-minute incubation period at 10 µM concentration. Under identical conditions, avacopan exhibited higher levels of thiol adducts, including glutathione and cysteine conjugates.

The differences in total reactive conjugate peak areas were most significant at early time points, exceeding 100-fold at 5 and 10 minutes, and remained observable at 20 and 40 minutes with approximately 10-fold differences. Reactive metabolite formation serves as an early indicator of potential bioactivation-related safety risk in drug development.

Izicopan is an investigational oral C5aR1 inhibitor designed as a next-generation therapeutic targeting the complement system. Previous studies showed the compound does not inhibit cytochrome P450 3A4 enzyme and demonstrated tolerability in first-in-human studies with doses ranging from 3 mg to 240 mg single doses and 30 mg once daily to 90 mg twice daily for 14 days.

"These data provide additional insight into the mechanistic profile of izicopan," said Prof. Renfeng Guo, Chief Scientific Officer and Founder of InflaRx. "We believe that, if supported by clinical data, such properties may contribute to its overall differentiation within the C5aR inhibitor class."

The company is developing izicopan for inflammatory diseases including hidradenitis suppurativa. Phase 2a data showed reductions in abscesses, nodules, and patient-reported pain scores over four weeks of therapy.