InflaRx N.V. announced topline results from the multiple ascending dose (MAD) part of its randomized, double-blind, placebo-controlled Phase I trial for INF904, an orally administered low molecular weight C5aR inhibitor. The pharmacokinetic (PK) and pharmacodynamic (PD) parameters confirm the favorable data InflaRx reported recently from the single ascending dose (SAD) part of the study, which provides support for the best-in-class potential of this drug candidate. INF904 was well tolerated and there were no adverse safety events of concern after repeated dosing in participants over the entire tested dose range.

In the MAD part of the randomized, double-blind, placebo-controlled Phase I trial, 24 participants received multiple doses of INF904 for 14 days of either 30 mg once per day (QD), 30 mg twice per day (BID) or 90 mg BID. The study?s primary objective was to evaluate the safety and tolerability of repeated dosing. Several PK parameters were analyzed as secondary endpoints, and the effect of the dosing scheme on C5a-induced neutrophil activation in blood samples from the participants was also explored in an ex vivo assay.

The safety analysis of INF904 in the MAD part of the Phase I study demonstrated that it was well tolerated in participants over the entire dose range and resulted in no safety signals of concern. The overall percentage of adverse events (AEs) in INF904 treated participants was 77.8%, which was lower than the 83.3% observed in the placebo group. There were no serious or severe AEs observed at any dosing level.

Analysis of the PK profile showed that potential target AUC0-12h, Cmax, and trough values were achieved rapidly within 14 days of 30 mg BID dosing. INF904 exposure further increased proportionally with dosing up to 90 mg BID. These results were demonstrated even when participants ingested the drug in a fasted state, suggesting that food is not required to achieve potentially therapeutic drug levels.

Analysis of the PD profile showed that the blocking activity of C5a-induced neutrophil activation by INF904 reached equal to or above 90% over the 14-day dosing period for all tested doses in an ex vivo challenge assay where physiological and disease-relevant levels of C5a were added to blood samples provided by the trial participants. InflaRx previously reported the data from the SAD part of the trial with 62 healthy volunteers in a press release and conference call. The SAD part showed a favorable dose-proportional systemic exposure with desired blocking activity (>90%) of C5a-induced neutrophil activation at disease-relevant C5a levels for doses of 30 mg to 240 mg 24 hours post-administration.

In parallel, InflaRx has progressed with the development of a commercially viable formulation of INF904 which the Company plans to introduce into Phase II development towards the end of 2024. InflaRx is currently conducting additional required pre-clinical studies, including long-term chronic toxicology studies, to enable longer-term dosing of INF904 for chronic inflammatory diseases. InflaRx currently plans to initiate a short-term dosing Phase II study towards the end of 2024, followed by a longer-term dosing Phase II study in 2025.

Further details of this clinical development plan with selection of indications will be announced in due course. INF904 is an orally administered small molecule inhibitor of C5a-induced signaling via the receptor C5aR. INF904 showed anti-inflammatory therapeutic effects in several pre-clinical disease models.

Further, in contrast to the marketed C5aR inhibitor, in vitro experiments demonstrated that INF904 has minimal inhibition of the cytochrome P450 3A4/5 (CYP3A4/5) enzymes, which play an important role in the metabolism of a variety of metabolites and drugs, including glucocorticoids. Reported results from a first-in-human study demonstrated that INF904 is well tolerated in treated subjects and exhibits no safety signals of concern in single doses ranging from 3 mg to 240 mg or multiple doses ranging from 30 mg once per day (QD) to 90 mg twice per day (BID) for 14 days. Pharmacokinetic /pharmacodynamic data support best-in-class potential of INF904 with a =90% blockade of C5a-induced neutrophil activation achieved over the 14-day dosing period.

InflaRx plans to bring INF904 into clinical Phase II development towards the end of 2024.