(Bonum) A Novel Method for Generating Regulated Cytokine Therapeutics: Safety and Activity of a Conditionally Active cLAG3-IL2 Capable of Delivering IL-2 to LAG-3+ Cells While Remaining Inert on LAG-3- Cells

Introduction

IL-2 is a powerful cytokine, but it has seen limited use in the treatment of cancer due to itstoxicity. Additional strategies to address these limitations are still needed.

• Our (Bonum) proprietary dual-binding antibody (DBA)-based platform allows the creation of conditionally active immunocytokines.

• Conditionally active LAG3-IL2 (cLAG3-IL2) specifically targets IL-2 to LAG-3-expressing antigen-experienced T cells while remaining inactive on the majority of IL-2R⁺ cells. This combines the IL-2 cis-targeting activity of a LAG3-IL2 immunocytokine when bound toLAG-3 with the “offness” of an IL-2 neutralizing antibody when unbound.

• In vitro activity of cLAG3-IL2 on reporter cell lines and LAG-3⁺ human T cells demonstrates conditional IL-2 signaling dependent on LAG-3 binding.

• In syngeneic mouse tumor models, cLAG3-IL2 inhibits tumor growth while avoiding clinical signs of IL-2 toxicity, even at high doses.

• cLAG3-IL2 drives the expansion and activation of tumor-specific CD8+ T without increasing peripheral IL-2R+ NK cell or T cell numbers.

‍