Background KINE-101, a novel synthetic nonapeptide, is being developed for the treatment of rheumatoid arthritis with a distinctive mode of action. A study using a collagen-induced arthritis (CIA) mouse model showed that KINE-101 suppressed cartilage damage through inhibiting osteoclastogenesis. KINE-101 showed its therapeutic effects in suppressing auto-immune responses by activating Regulatory T cells (Tregs), a specialized subpopulation of T cells, in in-vivo studies using mouse models of RA. Following the in-vivo studies, the phase 1 clinical study for KINE-101 was conducted to assess the safety and tolerability in healthy subjects in the US. Methods Total 40 healthy subjects were enrolled to assign in 5 cohorts. Each cohort included 8 subjects composed of 6 active and 2 placebo treatment. The subjects of first 4 cohorts were administrated with 10, 30, 100, 300 mg of KINE-101 by intravenous (IV) infusion as single ascending doses (SAD), and the Cohort 5 subjects were subcutaneously (SC) injected with 96.8 mg of KINE-101. Results Except for 2 subjects in placebo group, all subjects completed the study. All the randomized subjects were included in the safety evaluation. No deaths, SAEs (Serious Adverse Events), or AEs (Adverse Events) leading to discontinuation were reported during the study periods. While total 9 TEAEs (Treatment-Emergent Adverse Events) were reported, all were assessed as mild. It included 3 headaches, 1 catheter site edema, 1 contusion and 1 nasal congestion in the treatment group, and 1 catheter site pain, 1 oral contusion and 1 COVID-19 infection in the placebo group. Oral contusion and COVID-19 occurred in the same subject, and all the other events were singular TEAEs reported in individual subjects. No injection site reactions were reported and no clinically significant changes in any laboratory values were noted. In terms of pharmacokinetic (PK) profile, KINE-101 was observed in the blood samples during and up to 5 minutes after infusion. Conclusion In the phase I clinical study, Treg activator KINE-101 demonstrated a favorable safety and tolerability profile. The most common AEs were headaches reported in 3 subjects, but all were mild and transient events. As typically seen in peptide drugs, KINE-101 has a short half-life. However, given that KINE-101 uses Treg as a proxy to exerts anti-inflammatory effects, its pharmacodynamic (PD) activity is likely to last longer. The next stage for KINE-101 will proceed to oral formulation and the Phase 2 clinical study in RA patients.
