Nektar Therapeutics (NKTR) H.C. Wainwright 3rd Annual BioConnect Investor Conference 2025 summary

Rezpegaldesleukin development history

• Rezpegaldesleukin was invented using the native IL-2 protein sequence, conjugated with polymer chemistry to achieve Treg specificity and selectivity.

• Entered a partnership with Eli Lilly in 2017, completing nine clinical studies across four autoimmune diseases and healthy volunteers.

• Collaboration with Eli Lilly ended in April 2023, making rezpegaldesleukin a wholly owned asset.

Clinical data and study design

• Phase I-B in atopic dermatitis showed dose-dependent efficacy, rapid onset, and remissive potential lasting 36 weeks post-treatment.

• Error in EASI score calculation by a third-party CRO under Eli Lilly was corrected, revealing a greater drug effect; corrected data published in Nature Communications and presented at EADV 2023.

• Phase II-B study in atopic dermatitis enrolled 400 patients, extended dosing to 16 weeks, and included maintenance arms with various dosing regimens.

• Three dose levels are being tested to observe dose response, aiming to replicate the 83% EASI score reduction seen in phase I-B.

Mechanism of action and differentiation

• Rezpegaldesleukin is an agonist that stimulates regulatory T cells, unlike most AD drugs which are antagonists.

• The mechanism aims to restore immune balance, potentially explaining the long duration of efficacy after dosing ends.