ATP-dependent IFN- α is designed to avoid the systemic toxicity associated with recombinant IFN- α therapy. While in circulation, the therapeutic remains in an inactive conformation. Upon binding to extracellular ATP in the tumor microenvironment, ATP-dependent IFN- α undergoes a conformational change, and the IFN- α component becomes accessible to its cell surface receptor. IFN- α then drives anti-tumor immunity through signaling in multiple tumor-resident immune cell populations.

LAG-3 dependent IL-2 is designed to direct IL-2 activity to tumor-reactive T cells. LAG-3 is absent on the majority of T cells in circulation. Directing IL-2 activity specifically to LAG-3+ T cells has the potential to stimulate the anti-tumor T cell response while minimizing systemic toxicity. Preclinical Development of cLAG3-IL2 commenced Q3 2024.

LRRC15-dependent anti-TGFβR2 is designed to be inactive in circulation and avoid systemic TGF-β inhibition. LRRC15 is highly expressed on suppressive cancer-associated fibroblasts (CAFs). Upon binding to LRRC15, the therapeutic undergoes a conformational change to reveal the anti-TGFβR2 component, which will block TGFβR2. Inhibition of TGF-β signaling in LRRC15-expressing CAFs reverses their immunosuppressive phenotype, reduces tumor collagen content, and allows increased T cell infiltration.

PD-L1-dependent IFN-α is designed to avoid the systemic toxicity associated with recombinant IFN-α therapy. Upon binding to PD-L1, PD-L1-dependent IFN-α undergoes a conformational change, and the IFN-α component becomes accessible to its cell surface receptor.