Selective expansion of regulatory T cells by NKTR-358 in healthy volunteers and patients with systemic lupus erythematosus.

To evaluate NKTR-358, a polyethylene glycol-interleukin-2 conjugate composition designed to selectively induce regulatory T cells (Tregs), in first-in-human studies. Healthy volunteers and patients with systemic lupus erythematosus (SLE) received single- or multiple-dose (biweekly) NKTR-358 or placebo in two sequential, randomized, phase 1 studies (single ascending dose [SAD; NCT04133116] and multiple ascending dose [MAD; NCT03556007]). Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics (PK) and immune effects of NKTR-358; exploratory objectives included effects on SLE disease activity. There were eight ascending dose cohorts in the SAD study (0.3-28.0 μg/kg: n = 76; placebo: n = 24) and four in the MAD study (3-24.0 μg/kg: n = 36; placebo: n = 12). Most adverse events (AEs) were grade 1-2 injection-site reactions, with no treatment-related serious or severe AEs, or deaths. PK data showed dose proportionality and prolonged exposure (mean half-life: 7.4-12.9 days). Dose-dependent, selective, and sustained increases in percentages and absolute numbers of total CD4 NKTR-358 was well tolerated, had a suitable PK profile for biweekly dosing, and led to marked and selective dose-dependent increases in CD25

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Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CF, RF, VC, RL, ID, ND, CH, JG, NH, JZ and BK report financial support was provided by Nektar Therapeutics. CF reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. RF reports a relationship with Nektar Therapeutics that includes: consulting or advisory. RF reports a relationship with Genentech/Roche that incudes personal fees and grants. RF reports a relationship with AstraZeneca that includes: consulting or advisory. RF reports a relationship with Mallinckrodt Pharmaceuticals that includes: consulting or advisory. VC reports a relationship with AbbVie Inc that includes: funding grants. VC reports a relationship with Amgen Inc that includes: funding grants. VC reports a relationship with Boehringer Ingelheim Corp USA that includes: funding grants. VC reports a relationship with Boston Pharmaceuticals that includes: funding grants. VC reports a relationship with Eli Lilly and Company that includes: funding grants. VC reports a relationship with EMD Serono Inc that includes: funding grants. VC reports a relationship with Genentech that includes: funding grants. VC reports a relationship with GlaxoSmithKline USA that includes: funding grants. VC reports a relationship with Merck & Co Inc that includes: funding grants. VC reports a relationship with Nektar Therapeutics that includes: funding grants. VC reports a relationship with Novartis that includes: funding grants. VC reports a relationship with Pfizer that includes: funding grants. VC reports a relationship with Roche that includes: funding grants. VC reports that Pinnacle Research Group/Anniston Medical Clinic also received funding from Astellas Pharma Global Development Inc. RL reports a relationship with Gilead Sciences Inc that includes: consulting or advisory. RL reports a relationship with Exagen Inc that includes: consulting or advisory. RL reports a relationship with Myriad Genetics Inc that includes: consulting or advisory. RL reports a relationship with Sanofi that includes: paid expert testimony and speaking and lecture fees. RL reports a relationship with Regeneron Pharmaceuticals Inc that includes: paid expert testimony and speaking and lecture fees. RL reports a relationship with Bristol Myers Squibb Co that includes: paid expert testimony and speaking and lecture fees. RL reports a relationship with AbbVie that includes: paid expert testimony and speaking and lecture fees. ND reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. CH reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. JG reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. NH reports a relationship with GlaxoSmithKline that includes: employment. DD reports a relationship with PRA Health Sciences that includes: employment. DD reports a relationship with ICON plc that includes: employment. JZ reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. BK reports a relationship with Nektar Therapeutics that includes: employment and equity or stocks. ID has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.