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EGF PTI MECHANISM OF ACTION
Bioven has conducted considerable mechanistic work to establish the mode of action of EGF PTI.

Experiments in cell lines derived from NSCLC patients were carried out for Bioven in Barcelona and the results are summarized in the charts below. They show the effect of anti-EGF on the inhibition of activation of four different cell lines representing patients with the most critical mutations in NSCLC.

The cell line with a single mutation in EGFR corresponds to patients that are treated with Erlotinib or Gefitinib. It is noteworthy that antibodies to EGF inhibit strongly the EGFR/EGF pathway in this EGFR mutated cell line. Pre-clinical Studies with anti-EGF in NSCLC Cell Lines. Cell line H1975, with a double mutation in EGFR, corresponds
to patients who may be treated with the same tyrokinase inhibitors as above but who do not respond to this therapy. In contrast anti-EGF antibodies do inhibit activation of the EGFR/EGF pathway, though it is less pronounced compared with wild type EGFR cell lines and occurs only at higher anti-EGF concentrations.

Interestingly cell line H2228 harbors translocation in the ALK gene, representing the cohort of patients treated with Crizotinib. It is noteworthy that anti-EGF antibodies do inhibit all components of the pathways tested (EGFR, ALK, ERK).

The results support the mechanism of action of EGF PTI and suggest that mutations in key genes do not influence the effect of anti-EGF in silencing the EGFR/EGF pathway.
Pre-clinical studies with anti-EGF in NSCLC Cell Lines