Safety and Pharmacokinetic Results from the First-in-Human Study with Intravenously Administered OMN6 (A Poster)

Background

Serious Gram-negative bacterial infections, particularly those caused by Acinetobacter baumannii (AB), pose a significant global health threat due to increasing antibiotic resistance (1-2).  OMN6 is a novel, biochemically-engineered antimicrobial peptide with a unique and new mechanism of action, selective for Gram-negative bacteria with minimal potential to develop resistance (3-4).

Methods

In a randomized, double-blind dose escalation study, nine cohorts (per cohort 6 subjects on OMN6 and 2 subjects on placebo) of healthy young male and female adult volunteers, received daily doses from 7.5 to 300 mg OMN6, as a single, double or triple 3-hours infusions with a 5 hours wash-out period between subsequent infusions. Safety and tolerability assessments,  and pharmacokinetic blood sampling occurred at pre-defined timepoints. All blood samples for the pharmacokinetic evaluation were analyzed with a validated LC/MS/MS assay. All safety, tolerability and pharmacokinetic results were descriptively analyzed.

Results

There were no serious adverse events or premature drop-outs. All safety (vital signs, ECG, safety labs in blood and urine, physical examinations, local tolerability) and tolerability (adverse events) parameters did not show a dose or time dependent effect. Adverse events were mild and transient. All treatments were well tolerated.

Single infusions of OMN6 show dose (Cmax) or near dose (AUCinf) dependent pharmacokinetics. Upon single infusions, the half-life increases from 0.08h at 7.5 mg to about 0.9h at 80 and 100 mg. After two or three infusion periods, there were no indications of an accumulation of OMN6, and the pharmacokinetic behavior of OMN6 is not affected by the number of infusions. There are no indications of a gender dependent effect on the pharmacokinetics of OMN6.

Conclusion

OMN6, upon one, two or three subsequent infusion periods of 3 hours each and up to a maximum total daily dose of 300 mg, has a favorable safety, tolerability and pharmacokinetic profile in healthy young volunteers. The reached OMN6 exposures showed efficacy in pre-clinical infection models4. The results support further clinical development of OMN6 as a potential therapeutic option for Gram-Negative Pathogen AB infections.

References

1. Centers for Disease Control and Prevention (2019). Antibiotic resistance threats in the US.
2. Tacconelli E et al., Lancet Infect Dis. (2018), 18(3):318-327.
3. Mandel S, et al. Sci Rep. (2021), 11(1):6603.
4. Michaeli J, et al. Antibiotics (2022);11(9):1201.