InflaRx N.V. announced its topline results from the single ascending dose (SAD) part of its randomized, double-blind, placebo-controlled Phase I trial of the orally administered, low molecular weight C5aR inhibitor INF904. In the SAD part of the study, INF904 demonstrated an excellent safety and tolerability profile as well as a very favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile, confirming INF904´s best-in-class potential. The SAD part of the Phase I first-in-human trial enrolled 62 healthy volunteers within six different dosing groups from 3 mg to 240 mg who were randomly assigned to receive INF904 or a placebo.

Different drug concentrations were tested for the 60 mg dosing group. The main objectives were to assess safety and tolerability of single ascending doses under fasting conditions. Secondary endpoints included several PK parameters, and the effect of INF904 on C5a-induced neutrophil activation in blood samples from treated volunteers ex vivo also was explored.

The results show that INF904 was well tolerated in treated patients and resulted in no safety signals of concern in single doses ranging from 3 mg to 240 mg. The overall percentage of adverse events (AEs) was lower in the INF904 treated patients compared to the placebo group, and no serious or severe AEs were observed at any dosing level. No related AEs were reported in conjunction with INF904 dosing.

Analysis of INF904 PK in subject plasma samples revealed sustained exposure to INF904 with six hours to maximum concentration (tmax). INF904 plasma levels were dose proportional for systemic exposure (AUClast) and nearly dose proportional for maximum concentration (Cmax) over the dose range used in the study. With the 30 mg dose, INF904 reached a Cmax of 289 ng/ml with an AUClast of 5197 h.ng/ml, which are approximately 3-fold and 10-fold, respectively, higher than the published Phase I data from the only marketed comparator Single doses of 30 mg or higher of INF904 achieved =90% blocking of C5a induced up-regulation of the activation marker CD11b on neutrophils in plasma samples from subjects ex vivo at 24 hours post dosing.

This inhibition was achieved when 12.6 nM recombinant C5a was added as stimulus in this assay, a C5a concentration which can be observed in patients with severe inflammatory conditions such as the immuno-dermatological disease, hidradenitis suppurativa, or during life-threatening inflammation (e.g., in critically ill COVID-19 patients or septic patients). Thus, INF904 inhibition of C5a-induced neutrophil activation in human plasma achieved the set goal for effective C5aR control at disease relevant C5a levels. The MAD part of the Phase 1 trial is ongoing, and the Company expects to present results from the approximately 24 healthy volunteers at the beginning of 2024.

InflaRx is currently preparing to initiate additional required pre-clinical studies, including chronic toxicology studies, for the future clinical development of INF904 in chronic inflammatory diseases. In parallel, the Company is evaluating select potential indications for future development.