Introduction Pegylated uricases are a promising but highly immunogenic therapy for severe gout. Preclinical studies have shown the ability of synthetic vaccine particles containing rapamycin (SVP-R) to inhibit the formation of ADAs against pegsiticase, a pegylated uricase.¹ Here we report initial data on the safety, immunogenicity and activity of an ongoing Phase 2 study of SEL-212, a novel combination therapy consisting of pegsiticase and SVP-R.

Objectives Evaluate the ability of monthly doses of SEL-212 to mitigate the immunogenicity of pegsiticase and enable sustained control of sUA in gout patients.

Methods Patients with symptomatic gout and elevated sUA (≥6 mg/dL) were treated with fixed doses of pegsiticase (0.2 mg/kg or 0.4 mg/kg) alone or co-administered with SVP-R (0.05, 0.08, or 0.1 mg/kg). SEL-212 was infused in 28 day cycles x3 doses followed by challenge with pegsiticase alone on 28 day cycles x2 doses. Safety, tolerability, sUA, and ADAs were monitored

Results In the SEL-212 Phase 1b study, 70% of patients administered 0.4 mg/kg pegsiticase with a mid-dose of 0.1 mg/kg SVP-R showed low or no ADA formation correlating with sustained low sUA levels for at least 30 days after a single dose, compared to 20% for patients treated with pegsiticase alone. In the ongoing Phase 2 study, the majority of patients receiving 0.1 mg/kg SVP-R administered with either 0.2 or 0.4 mg/kg pegsiticase also showed low or no ADAs and maintained low sUA levels after 3 monthly doses of SEL-212, indicating sustained activity with repeated doses of SEL-212. However after 2 subsequent doses of pegsiticase alone, a drop in activity was noted. These data suggest that either a higher dose of SVP-R or the addition of SVP-R at the 4th and 5th dose may be required to sustain activity through 5 months. Currently patients are being dosed with 0.15 mg/kg SVP-R, a dose level which enabled sustained control of sUA levels in all patients in Phase 1b. SEL-212 was generally well tolerated and associated with a low rate of gout flare rates compared to those treated with pegsiticase alone.

Conclusions SVP-R showed a dose-dependent reduction in ADAs and enabled sustained control of sUA with repeated dosing of SEL-212. SVP-R is a promising approach to prevent the formation of ADAs against immunogenic biologic therapies.

Reference

1. . Kishimoto TK, et al. Nature Nanotechnol2016;11:890–899.

Acknowledgements We thank the patients that participated in these studies, the clinical study site investigators, and the entire SEL-212 project team.

Disclosure of interest E. Sands Employee of: Selecta Biosciences, A. Kivitz: None declared, W. DeHaan Employee of: Selecta Biosciences, L. Johnston Employee of: Selecta Biosciences, T. Kishimoto Employee of: Selecta Biosciences