Fig. 7: Evaluation of the antitumor activity and in vivo PK of EGFR-XPAT prototype.
a, In vitro activity of the EGFR-XPAT protein and its corresponding unmasked EGFR-TCE (EGFR−uTCE) against HT-29 (BRAFmut) cells (effector–target ratio, 5:1; n = 2 technical replicates at each concentration tested within one single experiment). Extended Data Table 1 provides a summary of EC50 values for unmasked EGFR-TCE and EGFR-XPAT protein in the cytotoxicity assays. b, TGI in the HT-29 huPBMC-engrafted xenograft model following i.v. administration of EGFR-XPAT protein (TIW dosing starting on day 14 post-tumor implantation; n = 6 mice for each concentration tested within one single experiment) and EGFR-uTCE (TIW dosing starting on day 14 post-tumor implantation; n = 6 mice for each concentration tested within one single experiment); P < 0.0001 for both versus vehicle at day 26 (mixed-effects multiple comparison analyses followed by Tukey’s post hoc test). The average body weight of the mice bearing tumor xenografts remained generally stable for the duration of the experiment following dosing with the EGFR-XPAT proteins or the vehicle control. c, PK following a single dose of EGFR-XPAT protein and EGFR-uTCE in NHPs. Sparse data were available for the unmasked EGFR-TCE due to PK assay sensitivity (lower limit of quantification ∼540 pM). Data represent mean plasma concentration based on a single plasma sample collected per time point from each NHP following administration of EGFR-XPAT protein (1 mg kg−1, n = 1 NHP; 0.46 mg kg−1, n = 2 NHPs; 0.23 mg kg−1, n = 2 NHPs; 0.0255 mg kg−1, n = 2 NHPs; 0.0085 mg kg−1, n = 2 NHPs) or EGFR-uTCE (0.033 mg kg−1 d−1, n = 1 NHP) within one single experiment.
