Results Presented at the American Association for Cancer Research 2014 Annual Meeting
NEW YORK, NY, USA I April 7, 2014 I Kadmon Corporation, LLC, today announced the presentation of preclinical data demonstrating the activity, in trastuzumab (Herceptin®) resistant HER2+ breast cancer, of KD019, the Company’s orally bioavailable spectrum selective small molecule kinase inhibitor of Src, HER2, EGFR and VEGFR2/KDR. The data were presented at the American Association for Cancer Research 2014 Annual Meeting (AACR 2014) taking place April 5-9, 2014, in San Diego, California.
In recent years, Src has emerged as a critical convergent node downstream of multiple signaling cascades initiated by receptor tyrosine kinases, most notably HER2, EGFR and IGF-1R. Crosstalk between Src and these receptors facilitates tumor growth and, in patients with HER2-amplified breast cancer, where Src is upregulated, may confer resistance to anti-HER2 therapies such as trastuzumab.
In the presented data, KD019 was shown to rapidly and effectively inhibit tumor growth in trastuzumab resistant models, both in vitro and in vivo. In vitro, KD019 demonstrated potent inhibition of HER2, EGFR and Src signaling in several trastuzumab resistant cell lines, as well as inhibition of c-Met activation, another pathway by which tumors may escape HER2 targeted therapies. KD019 was also shown to be more potent than either the HER2/EGFR inhibitor lapatinib or EGFR inhibitor erlotinib in inhibiting trastuzumab resistant breast cancer cell growth in vitro. In vivo, results demonstrate that once daily dosing of KD019 strongly inhibited tumor growth in xenograft models of trastuzumab resistance and that Src activity was inhibited in KD019 treated tumors as early as 24 hours after drug administration.
Further, the significance of inhibiting the combination of tumor drivers targeted by KD019 was underscored by its 10 fold greater potency in inhibiting growth of trastuzumab resistant cells when compared to saracatinib, a selective Src inhibitor.
“KD019 is a unique molecule, with activity against a combination of key tumor drivers, including Src, HER2, EGFR and VEGFR2/KDR, that may provide a distinct advantage over single-target agents, such as Src inhibitors, or drug combinations that would inhibit the same spectrum of targets,” said Samuel D. Waksal, Ph.D., Chairman and CEO of Kadmon. “Further, as an effective penetrant of the blood brain barrier, KD019 holds potential in treating tumors metastasized to the brain — an area where currently approved therapies demonstrate little benefit. We look forward to initiating clinical trials of KD019 in women with previously treated, Src- and HER2-positive, metastatic breast cancer, both with and without metastases to the brain, in the near future.”
About Kadmon Corporation
Kadmon Corporation, LLC, is a global company built on a 21st-century paradigm for the translation of innovative science into treatment. The company currently offers products and services for the treatment and management of liver diseases, and is pioneering novel medicines in areas of serious disease, including oncology, immunology and infectious, neurodegenerative and ophthalmic diseases. Emphasizing emerging concepts in molecular biology and genomics, Kadmon is developing treatments and treatment combinations that target the metabolomics and signaling pathways associated with disease, with the goal of addressing some of today’s most pressing areas of unmet medical need. For more information, visit www.kadmon.com.
SOURCE: Kadmon
Post Views: 71
Results Presented at the American Association for Cancer Research 2014 Annual Meeting
NEW YORK, NY, USA I April 7, 2014 I Kadmon Corporation, LLC, today announced the presentation of preclinical data demonstrating the activity, in trastuzumab (Herceptin®) resistant HER2+ breast cancer, of KD019, the Company’s orally bioavailable spectrum selective small molecule kinase inhibitor of Src, HER2, EGFR and VEGFR2/KDR. The data were presented at the American Association for Cancer Research 2014 Annual Meeting (AACR 2014) taking place April 5-9, 2014, in San Diego, California.
In recent years, Src has emerged as a critical convergent node downstream of multiple signaling cascades initiated by receptor tyrosine kinases, most notably HER2, EGFR and IGF-1R. Crosstalk between Src and these receptors facilitates tumor growth and, in patients with HER2-amplified breast cancer, where Src is upregulated, may confer resistance to anti-HER2 therapies such as trastuzumab.
In the presented data, KD019 was shown to rapidly and effectively inhibit tumor growth in trastuzumab resistant models, both in vitro and in vivo. In vitro, KD019 demonstrated potent inhibition of HER2, EGFR and Src signaling in several trastuzumab resistant cell lines, as well as inhibition of c-Met activation, another pathway by which tumors may escape HER2 targeted therapies. KD019 was also shown to be more potent than either the HER2/EGFR inhibitor lapatinib or EGFR inhibitor erlotinib in inhibiting trastuzumab resistant breast cancer cell growth in vitro. In vivo, results demonstrate that once daily dosing of KD019 strongly inhibited tumor growth in xenograft models of trastuzumab resistance and that Src activity was inhibited in KD019 treated tumors as early as 24 hours after drug administration.
Further, the significance of inhibiting the combination of tumor drivers targeted by KD019 was underscored by its 10 fold greater potency in inhibiting growth of trastuzumab resistant cells when compared to saracatinib, a selective Src inhibitor.
“KD019 is a unique molecule, with activity against a combination of key tumor drivers, including Src, HER2, EGFR and VEGFR2/KDR, that may provide a distinct advantage over single-target agents, such as Src inhibitors, or drug combinations that would inhibit the same spectrum of targets,” said Samuel D. Waksal, Ph.D., Chairman and CEO of Kadmon. “Further, as an effective penetrant of the blood brain barrier, KD019 holds potential in treating tumors metastasized to the brain — an area where currently approved therapies demonstrate little benefit. We look forward to initiating clinical trials of KD019 in women with previously treated, Src- and HER2-positive, metastatic breast cancer, both with and without metastases to the brain, in the near future.”
About Kadmon Corporation
Kadmon Corporation, LLC, is a global company built on a 21st-century paradigm for the translation of innovative science into treatment. The company currently offers products and services for the treatment and management of liver diseases, and is pioneering novel medicines in areas of serious disease, including oncology, immunology and infectious, neurodegenerative and ophthalmic diseases. Emphasizing emerging concepts in molecular biology and genomics, Kadmon is developing treatments and treatment combinations that target the metabolomics and signaling pathways associated with disease, with the goal of addressing some of today’s most pressing areas of unmet medical need. For more information, visit www.kadmon.com.
SOURCE: Kadmon
Post Views: 71
