Kiniksa presents KPL-716 data at the Society for Investigative Dermatology
Kiniksa announced that it presented clinical and preclinical data for KPL-716, an investigational fully-human monoclonal antibody that targets oncostatin M receptor beta, or OSMRss, the shared receptor subunit for interleukin-31, or IL-31, and oncostatin M, or OSM signaling. The data were included in oral and poster presentations at the Society for Investigative Dermatology. Data from the adjunctive therapy period of Kiniksa's Phase 1a/1b clinical trial of single-dose KPL-716 7.5 mg/kg intravenous, or IV, in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus versus placebo IV showed a sustained anti-pruritic effect of OSMRss inhibition through at least week 6. The data reinforce and extend the previously-reported findings from the Phase 1a/1b monotherapy period, which provided evidence of target engagement and an early signal of efficacy in reducing pruritus and disease severity. Data from Kiniksa's longitudinal observational study in prurigo nodularis, or LOTUS-PN, suggest that the OSMRss axis may play a role in the pathogenesis of prurigo nodularis given its prevalent expression in lesional prurigo nodularis. IL-31 messenger ribonucleic acid, or mRNA, was expressed in approximately two-thirds of lesional biopsies from prurigo nodularis patients with Worst-Itch Numeric Rating Scale of 7 compared to one-tenth in healthy volunteers. Additionally, lesional biopsies from prurigo nodularis patients contained mononuclear cells expressing OSM, OSMRss, IL-31 and IL-31Ra protein compared with non-lesional biopsies. OSM is involved in Type 2 T helper, or TH2, inflammation, epidermal integrity and fibrosis. Data highlight the therapeutic potential of KPL-716, through the inhibition of OSM activity, in TH2 mediated diseases discrete from inhibition of IL-31. Further, the data show induction of MCP-1 and mRNA by OSM in both cell types tested and significant attenuation by KPL-716 of the cellular MCP-1 response to OSM and the synergistic response to OSM and interleukin-4, or IL-4. Importantly, these data showed that OSM synergizes with IL-4 and interleukin-13, or IL-13, and that leukemia inhibitory factor and IL-31 do not. KPL-716 data from a preclinical model exhibited dose- and time-dependent anti-pruritic effects. Pharmacokinetic and pharmacodynamic correlation established an efficacious concentration range of 5-8.5 microg/ml in cynomolgus monkeys, at or above which KPL-716 provided protection from pruritus induced by supra-physiologic challenges of IL-31. The results with single dose KPL-716 IV were corroborated with repeat-dosed KPL-716 subcutaneous in various dosing regimens and were predictive of the reduction in pruritus observed in the Phase 1a/1b clinical trial of single-dose KPL-716 7.5 mg/kg IV in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritis.