CK-101 is an oral, third generation covalent inhibitor against selective mutations of EGFR. Activating mutations in the tyrosine kinase domain of EGFR are found in approximately 20% of patients with advanced NSCLC. Compared to chemotherapy, first generation EGFR inhibitors significantly improved ORR and progression free survival in previously untreated NSCLC patients carrying EGFR mutations. However, tumor progression could develop due to resistance mutations, often within months of treatment with first generation EGFR inhibitors.
The EGFR T790M “gatekeeper” mutation is the most common resistant mutation found in patients treated with first generation EGFR inhibitors. The mutation decreases the affinity of first generation inhibitors to EGFR kinase domain, rendering the drugs ineffective. Second generation EGFR inhibitors have improved in vitro potency against the T790M mutation, but have not provided meaningful benefits in NSCLC patients due to toxicity from inhibition of the wildtype EGFR activities.
The third generation EGFR inhibitors are designed to be highly selective against the T790M mutation while sparing wildtype EGFR, thereby improving tolerability and safety profiles. In clinical studies, third generation EGFR inhibitors have demonstrated robust response in second-line NSCLC patients carrying the T790M mutations, with an ORR of up to 50 to 60%. In addition, some of the third generation inhibitors are also active against activating EGFR mutations seen in first-line NSCLC patients such as L858R and del 19, and have shown efficacy in monotherapy studies.
We plan to develop CK-101 for oncology indications, including, but not limited to, the treatment of NSCLC patients carrying the susceptible EGFR mutations. These include the EGFR T790M mutation in the second-line NSCLC patients as well as the EGFR L858R and del 19 mutations in first-line NSCLC patients. We believe that CK-101 has the potential to be effective in these oncological indications as a monotherapy or in combination with other anti-tumor immune response potentiating compounds and other targeted therapies. Existing preclinical data from other programs support the combination of third generation EGFR inhibitor with checkpoint inhibitors (PD-1 or PD-L1), cMET inhibitors, or MEK inhibitors.
In March 2015, we entered into an exclusive license agreement with NeuPharma to develop and commercialize novel covalent third generation EGFR inhibitor on a worldwide basis outside of certain Asian countries. In August 2016, the FDA accepted our IND application, and in September 2016 we dosed the first patient in a Phase 1/2 clinical trial.