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Selective EGFR inhibitor for the treatment of non-small cell lung cancer

We offer a focused drug development project to use a clinically validated biomarker and molecular diagnostic method to select lung cancer patients for personalized treatment with our patented drug candidate. The expected clinical efficacy of the drug in the selected patient population is close to 100%. Therefore, the proof of clinical efficacy statistically requires only low cost clinical trials using small number of selected patients which can lead to fast-track market authorization.

Lung cancer is the most common cancer and leading cause of cancer related deaths. The target of our drug is the mutant form of EGFR (Epidermal Growth Factor Receptor) which is the most successfully targeted molecule for effective and selective treatment of lung cancer. The life of patients with this type of lung cancer can be prolonged with years with EGFR inhibitors. This is an unprecedented breakthrough in the treatment of this disease.

Our EGFR inhibitor drug candidate has a better selectivity profile than established competitive molecules on the market, therefore we expect less side effects. This is very important since patients have to be able to take the drugs for years. Our team has vast experience in both the development of kinase inhibitors and in the molecular diagnostics of activating mutations of EGFR. Our integrated drug discovery and molecular diagnostic development strategy has been recently accepted for publication in Nature Reviews Drug Discovery.

Results

Our lead compound (VI14442) inhibits EGFR with IC₅₀ = 2 nM in an in-house biochemical enzymatic assay. The table shows the excellent selectivity of the inhibitor (values are percentage inhibitions at 10 μM) determined in similar assays.

VI14442 was screened on a cellular selectivity panel containing 18 different cell lines and was shown to selectively inhibit the HCC827 cell line, a lung adenocarcinoma cell line with a sensitising mutation in the EGFR tyrosine kinase domain (IC₅₀ = 190 nM). In our endothel toxicity assay VI14442 was not cytotoxic (LD₅₀ > 50 μM) in contrast to Iressa (LD₅₀ = 24.5 μM). According to flow cytometry results, VI14442 induced apoptosis (in 62 percent of cells) in the HCC827 cell line, in contrast to the normal cell line, where the compound did not induce any apoptosis.