KDDF 2022: Triple action and pre-clinical safety profile of SLC-3010 Poster submission 

<Abstract>

SLC-3010, a novel IL-2 drug candidate which has been recently cleared Investigational New Drug(IND) from the U.S. Food and Drug Administration(FDA), is a noncovalent conjugate of human IL-2 and anti-IL-2(TCB2) antibody which blocks IL-2Rα binding site on IL-2 thereby selectively stimulating cancer-fighting CD8 and NK cells but not immuno-suppressive Treg cells. Previously, the superior anti-tumor efficacy of SLC-3010 was demonstrated in various settings of syngeneic tumor models and combination therapies with immune-checkpoint inhibitors (anti-PD-1, anti-CTLA-4), anti-VGEF (zaltrap), chemotherapy (Gemcitabine, 5-FU), cell-based therapy, cancer vaccine and radiotherapy. Pharmacokinetics (PK) and pharmacodynamics (PD) analysis revealed a potential multi-function of SLC-3010 as SLC-3010 and its metabolite TCB2 have distinct half-lives. SLC-3010 stimulates CD8 T cells, peaks on day 4, and then disappeared within 72 hours, indicating IL-2 dissociation from SLC-3010 after T cell stimulation. After this, IL-2-unbound TCB2 (free TCB2) remains for several weeks in the blood and is capable of re-conjugation with endogenous IL-2 thereby inhibiting Treg-homeostasis but stimulating CD8 T cells once again. In non-human primate studies, SLC-3010 successfully expanded CD8 and NK cells but not Tregs with a highly favorable safety profile. Overall, these findings suggest the potential of SLC-3010 as a promising anti-cancer drug.