On April 4, 2017 Checkpoint Therapeutics, Inc. ("Checkpoint") (OTCQX: CKPT), a Fortress Biotech (NASDAQ: FBIO) company, reported that preclinical data on its third-generation epidermal growth factor receptor ("EGFR") inhibitor, CK-101, and anti-programmed cell death ligand-1 ("PD-L1") antibody, CK-301, were presented this week in poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Fortress Biotech, APR 3, 2017, View Source [SID1234518456]). The data presented strongly support the clinical development of these therapies.

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James F. Oliviero, President and Chief Executive Officer of Checkpoint, said, "These encouraging preclinical data demonstrate the potential of our EGFR inhibitor and anti-PD-L1 checkpoint antibody to be effective new treatment options for patients suffering from cancer. We look forward to advancing these drug candidates through the stages of clinical development, both as monotherapies as well as in combination with each other."

Key conclusions from the posters are as follows:

CK-101 (RX518), a Mutant-Selective Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer (NSCLC)

CK-101 (also known as RX518) is a novel, irreversible, orally administered EGFR kinase inhibitor that specifically targets the mutant forms of EGFR, including T790M, while exhibiting minimal activity toward the wild-type EGFR. Cell proliferation assays in human cancer cell lines in vitro, and xenograft studies conducted in mouse models of NSCLC demonstrated:

CK-101 is a potent, mutant-selective inhibitor of both the activating (exon 19 deletion) and resistance mutations (L858R / T790M double mutation).

CK-101 inhibited tumor growth as a single agent in a NSCLC model with a single activating mutation (exon 19 deletion).

CK-101 showed dose-dependent inhibition of tumor growth as a single agent in a L858R / T790M double mutant NSCLC model.

CK-101 has little inhibitory potency toward wild-type EGFR (i.e., CK-101 was more than 100-fold less potent against wild-type EGFR than against L858R / T790M double mutation).

These data supported the initiation of a Phase 1/2 clinical trial in September 2016 (ClinicalTrials.gov: NCT02926768). The Phase 1 dose-escalation portion is ongoing, and Checkpoint expects to initiate the Phase 2 portion in patients with EGFR T790M mutation‐positive NSCLC cancer in the second half of 2017.

Preclinical Characterization of a Novel Fully Human IgG1 Anti-PD-L1 mAb CK-301

Based on the various assays performed, the poster concluded:
CK-301 is a high affinity PD-L1 specific fully humanized lgG1 antibody which blocks binding of PD-L1 to PD-1.

Activity of CK-301 in all assays tested was similar to anti-PD-L1’s used as active controls (surrogates of avelumab, atezolizumab or durvalumab).

Similar to the approved anti-PD-L1, avelumab, CK-301 has the potential to induce ADCC (antibody-dependent cell-mediated cytotoxicity).

A first-in-human Phase 1 study of CK-301 is planned to commence this year.

The posters are available on the Publications page within the Pipeline section of Checkpoint’s website,
www.checkpointtx.com.