IL-15 Superagonist Nanrilkefusp alfa

Nanrilkefusp alfa (formerly SOT101), recently given an international nonproprietary name designation by the World Health Organization, is a subcutaneously-administered IL-15 superagonist, that is fused to the sushi+ domain of the IL-15 receptor α. The drug has been precisely designed and optimized for its use as a potent immunotherapy by addressing two important design issues that limit current IL-2 and IL-15 approaches:

  1. Specificity for cytotoxic T and NK cells may provide a superior efficacy and safety profile: Nanrilkefusp alfa is designed to selectively bind only to cytotoxic T and NK cells, while avoiding other cell types that are associated with adverse events.
  2. Optimized half-life may improve efficacy by limiting T cell exhaustion: Nanrilkefusp alfa’s pharmacokinetic properties enable it to ideally stimulate T and NK cells through pulses in cytokine concentration, rather than tonic stimulation.

In Phase 1/1b, the AURELIO-03 trial of nanrilkefusp alfa demonstrated a favorable safety profile and encouraging efficacy signals both in monotherapy as well as in combination with KEYTRUDA® (pembrolizumab). Such efficacy signals were observed even in patients with checkpoint-inhibitor relapsed and refractory tumors. Interim results presented at the ASCO 2022 annual meeting demonstrated clinical benefit in 15 out of 19 patients receiving nanrilkefusp alfa in combination with pembrolizumab across all dose-levels. 

In July 2022, SOTIO announced dosing of the first patient in the AURELIO-04 Phase 2 trial of nanrilkefusp alfa in combination with pembrolizumab. AURELIO-04 was initiated in collaboration with MSD. The Phase 2 trial (NCT05256381) is an open-label, single-arm, multicenter study of nanrilkefusp alfa in combination with pembrolizumab to evaluate efficacy and safety in patients with selected advanced/refractory solid tumors, which is run under a clinical trial agreement with MSD. More information on the ongoing clinical trial can be found here. We are planning to launch the Phase 2 monotherapy study of nanrilkefusp alfa.