The highest non-severely toxic dose of LM-306 was determined to be 9 mg/kg in the DRF study and MTD was determined to be 18mg/kg in MTD study for male monkey. In summary, LM-306 showed high binding affinity to human IL13Rα2 expressing cells with potent cytotoxicity in vitro and significant in vivo inhibition of tumor growth, suggesting its therapeutic benefit in immuno-oncology.Summary of parameters of LM-106 and LM-306 binding affinity, internalization, ADCC and cytotoxicityAssayAntibody EC50 (nM)HEK293/H_IL-13Rα2U251A375SKMEL5Binding affinityLM-1060.990.210.570.1LM-3061.470.330.80.12InternalizationLM-1062.22-0.43-ADCCLM-1060.16-0.03-LM-3060.31-0.03-Cytotoxicity (IC50)LM-3060.030.050.010.005

ADCT-211 is an antibody-drug conjugate composed of HuCl47, a humanized IgG1 antibody directed against human IL13RA2, site-specifically conjugated using GlycoConnectTM technology to PL1801, which contains HydraspaceTM, a valine-alanine cleavable linker and the PBD dimer cytotoxin SG2000 (drug to antibody ratio ~ 1.8). Expression of membranous IL13RA2 was confirmed by IHC in a panel of primary and refractory GBM samples and malignant melanoma, highlighting them as potential indications for the clinical development of ADCT-211. In conclusion, ADCT-211 demonstrated potent and specific in vitro and in vivo anti-tumor activity and it was stable and well tolerated in the rat, warranting further development of ADCT-211 into the clinic in IL13RA2-expressing cancers.