On September 25, 2018 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported that positive preliminary safety and efficacy data from an ongoing Phase 1/2 clinical trial of CK-101 were presented yesterday in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto (Press release, Checkpoint Therapeutics, SEP 25, 2018, View Source [SID1234529735]). The oral presentation included further details on, and updates from, the dataset announced previously. CK-101 is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being evaluated in advanced non-small cell lung cancer (NSCLC).

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"The oral presentation included exciting updates to the data released in the abstract, including intracranial disease responses to treatment with CK-101 in patients with brain metastases present at baseline indicating that CK-101 may cross the blood-brain barrier to reach metastases in the central nervous system, as well as an additional partial response post-data cutoff in a T790M mutation-positive NSCLC patient that failed previous TKI therapy," said James F. Oliviero, President and Chief Executive Officer of Checkpoint Therapeutics. "Based on these data, we believe CK-101 has the potential to be an effective and differentiated treatment option in a potential $6 billion market currently dominated by one approved therapy."

Highlights from the Oral Presentation
• CK-101 was well-tolerated across multiple dose groups
– Most adverse events were Grade 1-2
– Maximum-tolerated dose was not defined; no reported dose-limiting toxicities or treatmentrelated
serious adverse events
– No events of interstitial lung disease, pneumonitis, QTc prolongation, cardiomyopathy, nail
toxicities, stomatitis or hyperglycemia, which are notable observed side effects of marketed
TKI therapies
• CK-101 demonstrates preliminary activity in EGFR mutation-positive NSCLC
– 75% (6 of 8) objective response rate (ORR) in treatment-naïve patients
– 100% (19 of 19) disease control rate (DCR), including 84% (16 of 19) of patients with target
lesion reductions versus baseline
– 60% (3 of 5) of patients with baseline brain metastases had intracranial disease response
• Enrollment in the trial is ongoing to identify the optimal dose to maximize therapeutic effect,
following which a Phase 3 trial is planned to initiate in 2019 in treatment-naïve EGFR mutationpositive
NSCLC patients.

The first-in-human, multicenter trial is evaluating CK-101 in NSCLC patients with EGFR mutations and other advanced malignancies (NCT02926768). Following dose escalation ranging from 100 mg to 1,200 mg/day in patients with any solid tumor where targeted EGFR was deemed reasonable, a first doseexpansion cohort was enrolled at 400 mg twice daily in patients with a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy. There was no limit on the number of prior lines of systemic therapy patients received prior to entering the trial.

A copy of the oral presentation slides is available on the Publications page in the Pipeline section of
Checkpoint’s website, www.checkpointtx.com.

About CK-101
CK-101 (also known as RX518) is an oral, third-generation, irreversible kinase inhibitor against selective mutations in the EGFR gene. Activating mutations in the tyrosine kinase domain of EGFR, such as L858R and exon 19 deletion, are found in approximately 20 percent of patients with advanced non-small cell lung cancer (NSCLC).

Compared to chemotherapy, first-generation EGFR inhibitors significantly improved objective response rate 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 resistance 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 potency against the T790M mutation, but have not provided meaningful benefits in NSCLC patients due to toxicity from also inhibiting wild-type EGFR. Third-generation EGFR inhibitors are designed to be highly selective against both EGFR-TKIsensitizing and resistance mutations, with minimal activity on wild-type EGFR, thereby improving tolerability and safety profiles.

Checkpoint Therapeutics is developing CK-101 for the treatment of NSCLC patients carrying the susceptible EGFR mutations. These include the EGFR T790M mutation in second-line NSCLC patients, as well as the EGFR L858R and exon 19 deletion mutations in first-line NSCLC patients. Checkpoint holds an exclusive worldwide license (except with respect to certain Asian countries) to CK‐101, which it acquired from NeuPharma, Inc., in 2015.