“We are pleased to grow the body of scientific data on the role of IL-31 and OSM in chronic pruritic conditions,” said
The data presentations were as follows:
Dr. Zamaneh Mikhak, of
- Data from the adjunctive therapy period (Day 29 to Day 60; topical corticosteroids allowed) of Kiniksa’s Phase 1a/1b clinical trial of single-dose KPL-716 7.5 mg/kg intravenous (IV) in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus versus placebo IV showed a sustained anti-pruritic effect of OSMRβ inhibition through at least week 6. The data reinforce and extend the previously-reported findings from the Phase 1a/1b monotherapy period (Day -7 to Day 28; topical corticosteroids not allowed), 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 (LOTUS-PN) suggest that the OSMRβ axis (IL-31, OSM, IL-31 receptor alpha (IL-31Rα) and OSMRβ) may play a role in the pathogenesis of prurigo nodularis given its prevalent expression in lesional prurigo nodularis. IL-31 messenger ribonucleic acid (mRNA) was expressed in approximately two-thirds of lesional biopsies from prurigo nodularis patients with Worst-Itch Numeric Rating Scale (WI-NRS) ≥ 7 compared to one-tenth in healthy volunteers. Additionally, lesional biopsies from prurigo nodularis patients contained mononuclear cells expressing OSM, OSMRβ, IL-31 and IL-31Rα protein compared with non-lesional biopsies.
- OSM is involved in Type 2 T helper (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 (IL-4). Importantly, these data showed that OSM synergizes with IL-4 and interleukin-13 (IL-13), and that leukemia inhibitory factor (LIF) and IL-31 do not.
- KPL-716 data from a preclinical model exhibited dose- and time-dependent anti-pruritic effects. Pharmacokinetic (PK) and Pharmacodynamic (PD) correlation established an efficacious concentration range of 5 – 8.5 μg/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.
The materials are available through the Investors and Media section of Kiniksa’s website (www.kiniksa.com).
KPL-716 is an investigational fully-human monoclonal antibody that targets OSMRβ, which mediates signaling of IL-31 and OSM, two key cytokines implicated in pruritus, inflammation and fibrosis. Kiniksa believes KPL-716 to be the only monoclonal antibody in development that targets both pathways simultaneously.
Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa has a pipeline of product candidates across various stages of development, focused on autoinflammatory and autoimmune conditions. For more information, please visit www.kiniksa.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: our belief of the potential for KPL-716 to be a differentiated mechanism for the potential treatment of a spectrum of chronic pruritic diseases; our plans and timing to commence an exploratory Phase 2 clinical trial of KPL-716; and our conclusions from interim pre-clinical and clinical trial data for KPL-716.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: changes between final data and any interim data we present; our potential inability to replicate in later clinical trials, including our Phase 2a clinical trial and planned exploratory Phase 2 clinical trial of KPL-716, the positive interim data from our pre-clinical and earlier clinical trials; potential impact of additional data from us or other companies; potential undesirable side effects caused by KPL-716; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities; and our reliance on third parties to manufacture KPL-716 and to conduct research, clinical trials and/or certain regulatory activities for KPL-716.
These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended
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Source: Kiniksa Pharmaceuticals, Ltd.