TIRmed Pharma hasrecently concluded a subcutaneous, non-GLP toxicity study in rats with notablesuccess. The primary goal of this investigation was to assess the occurrence ofside effects at exceptionally high dosage levels. A crucial insight from this studywas that the adverse effects identified align with the well-documented,class-specific side effects associated with oligonucleotides. This findingaffirms the safety profile of our lead candidate TIR-01, mitigating concernsabout unexpected adverse effects. Moreover, this outcome substantially reducesthe risk associated with forthcoming GLP toxicity studies by providingpreliminary evidence of their potential results.
In the study, thetoxicokinetics of TIR-01 were evaluated across three dosage groups of SPFWistar rats, administered once daily at the lower dose and every third day atthe higher doses. The duration of the study was 7 days. Plasma samples werecollected on Day 1 and Day 7 at specific intervals post-dose to establishindividual concentration-time profiles. The concentration of TIR-01 in ratplasma was quantified using a Peptide Nucleic Acid Anion-ExchangeHigh-Performance Liquid Chromatography (PNA-AEX-HPLC) assay. Toxicokineticparameters were derived from these profiles, employing nominal dose levels andsampling times for the non-compartmental analysis. All animals treated withTIR-01 demonstrated systemic exposure to the compound. Measurable plasmaconcentrations of TIR-01 persisted for up to 24 hours post-dose across alldosage levels, following both single and repeated subcutaneous doses.
TIR-01 was metabolizedwith a mean terminal elimination half-life ranging from 2.3 to 5.8 hours,indicating that exposure generally increased in a more than dose-proportionalmanner when comparing two dosage levels within the same regimen. No adverse clinicalsigns were observed at the lower doses.