CK-101 is an oral, third generation, irreversible kinase 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 also inhibiting wild-type EGFR.
The third generation EGFR inhibitors are designed to be highly selective against the T790M mutation while sparing wild-type 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 are developing CK-101 for 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. Existing preclinical data from other programs support the combination of third generation EGFR inhibitors with checkpoint inhibitors (PD-1 or PD-L1).
In March 2015, we entered into an exclusive license agreement with NeuPharma to develop and commercialize novel covalent third generation EGFR inhibitors on a worldwide basis outside of certain Asian countries. In August 2016, the FDA accepted our IND application and we initiated a Phase 1/2 clinical study in September 2016.