Preclinical data support novel mechanisms of action for anti-tumor activity targeting the KIT kinase for gastrointestinal stromal tumors (GIST) and combination with T-cell checkpoint inhibitors
NEW HAVEN, CT, USA I April 20, 2016 I Kolltan Pharmaceuticals, Inc., a privately held clinical-stage company focused on the discovery and development of novel antibody-based drugs targeting receptor tyrosine kinases (RTKs) for use in oncology and immunology, today announced the presentation of preclinical data relating to its KTN0158 drug development program at the AACR Annual Meeting, taking place in New Orleans, Louisiana, April 16-20, 2016. KTN0158 is a proprietary, clinical-stage, humanized anti-KIT IgG1 monoclonal antibody drug candidate that selectively and potently inhibits KIT and is being developed as a potential therapy for cancer and mast cell-related diseases.
“The compelling preclinical data that were presented at AACR support our plans to evaluate KTN0158 in combination with T-cell checkpoint inhibitors in the clinic near-term. This expands our current clinical focus beyond gastrointestinal stromal tumors (GIST) and further broadens the opportunity to investigate the treatment of cancer patients through targeting KIT, with potential to affect immunosuppressive mast cells and myeloid cells. Developing innovative biologics with a focus on RTKs expressed on innate immune cells is an exciting new area for Kolltan with KTN0158 in clinical development,” stated Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan.
Rich Gedrich, Ph.D., Senior Director of Translational Medicine of Kolltan, added, “KTN0158 represents a novel approach to inhibit KIT on tumor cells by blocking the dimerization of the receptor through an allosteric mechanism. Previous preclinical data have shown significant anti-tumor activity in KIT-driven tumors such as GIST, targeted in our Phase 1 trial of KTN0158, and now the current findings in combination with anti-PD-1 and anti-CTLA4 antibodies support a second distinct approach to develop KTN0158 as an anti-cancer therapy.”
Following are the key data and results from the two presentations at AACR relating to KTN0158:
On Sunday, April 17, KTN0158 was highlighted as a novel experimental treatment approach for GIST in an oral presentation titled “Experimental Treatment Options for Gastrointestinal Stromal Tumors with Primary or Secondary Resistance to Tyrosine Kinase Inhibitors”. The presentation reviewed previously disclosed preclinical data including:
- An overview of KTN0158’s unique mechanism of action which inhibits KIT activation by blocking receptor dimerization; and
- The preclinical activity of KTN0158 in GIST models with activating KIT mutations and also activity in dogs with spontaneous mast cell tumors driven by KIT activation.
On Tuesday, April 19, “Inhibition of KIT In Vivo Modifies Immune Cell Populations to Improve the Efficacy of Checkpoint Inhibitors in Syngeneic Mouse Tumor Models” (Abstract Number 4020), was presented in a poster session.
The poster presentation reported the following data and results:
- Enhanced anti-tumor activity with the combination of a surrogate mouse anti-KIT monoclonal antibody with either anti-PD-1 or anti-CTLA4 monoclonal antibodies in several syngeneic mouse tumor models; and
- Mechanistic studies showed a significant decrease in monocytic myeloid-derived suppressor cells (mMDSCs) in the tumor and in the spleen of the anti-KIT antibody treated groups. High levels of circulating mMDSCs have been associated with reduced survival in melanoma patients treated with ipilimumab or nivolumab.
The poster is available on the Kolltan website.
About KTN0158
KTN0158 is a proprietary, humanized monoclonal antibody designed using structure-based approaches to block the activation of KIT, an RTK that is expressed on many cancers and mast cells. There are currently no KIT-targeting antibodies on the market for any disease indication. In oncology, KIT is expressed in tumors such as GIST, melanoma, acute myeloid leukemia (AML), small cell lung cancer (SCLC), and others. Additionally, KIT is expressed in immune suppressive cells in the tumor microenvironment and thus may provide a novel combination treatment for immuno-oncology. Kolltan has initiated a Phase 1 study for the treatment of GIST and other KIT-expressing tumors (NCT02642016) and plans to move into combination studies with other targeted therapies and T cell checkpoint inhibitors.
About Kolltan Pharmaceuticals
Kolltan, a privately held clinical-stage company, is focused on the discovery and development of novel, antibody-based drugs targeting RTKs for the treatment of cancer and other diseases with significant unmet need. Kolltan’s founders and members of its management team have deep expertise and a proven track record in drug discovery, development, and commercialization of innovative therapeutics, including drugs targeting RTKs. Kolltan is working in close collaboration with the laboratory of Kolltan Co-Founder, Dr. Joseph Schlessinger, as well as the Yale University medical and scientific community. The Company has a broad and novel oncology and immunology portfolio of therapeutic biologics targeting multiple RTKs that are advancing in the clinic and are expected to generate multiple near-term milestones.
SOURCE: Kolltan Pharmaceuticals
Post Views: 133
Preclinical data support novel mechanisms of action for anti-tumor activity targeting the KIT kinase for gastrointestinal stromal tumors (GIST) and combination with T-cell checkpoint inhibitors
NEW HAVEN, CT, USA I April 20, 2016 I Kolltan Pharmaceuticals, Inc., a privately held clinical-stage company focused on the discovery and development of novel antibody-based drugs targeting receptor tyrosine kinases (RTKs) for use in oncology and immunology, today announced the presentation of preclinical data relating to its KTN0158 drug development program at the AACR Annual Meeting, taking place in New Orleans, Louisiana, April 16-20, 2016. KTN0158 is a proprietary, clinical-stage, humanized anti-KIT IgG1 monoclonal antibody drug candidate that selectively and potently inhibits KIT and is being developed as a potential therapy for cancer and mast cell-related diseases.
“The compelling preclinical data that were presented at AACR support our plans to evaluate KTN0158 in combination with T-cell checkpoint inhibitors in the clinic near-term. This expands our current clinical focus beyond gastrointestinal stromal tumors (GIST) and further broadens the opportunity to investigate the treatment of cancer patients through targeting KIT, with potential to affect immunosuppressive mast cells and myeloid cells. Developing innovative biologics with a focus on RTKs expressed on innate immune cells is an exciting new area for Kolltan with KTN0158 in clinical development,” stated Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan.
Rich Gedrich, Ph.D., Senior Director of Translational Medicine of Kolltan, added, “KTN0158 represents a novel approach to inhibit KIT on tumor cells by blocking the dimerization of the receptor through an allosteric mechanism. Previous preclinical data have shown significant anti-tumor activity in KIT-driven tumors such as GIST, targeted in our Phase 1 trial of KTN0158, and now the current findings in combination with anti-PD-1 and anti-CTLA4 antibodies support a second distinct approach to develop KTN0158 as an anti-cancer therapy.”
Following are the key data and results from the two presentations at AACR relating to KTN0158:
On Sunday, April 17, KTN0158 was highlighted as a novel experimental treatment approach for GIST in an oral presentation titled “Experimental Treatment Options for Gastrointestinal Stromal Tumors with Primary or Secondary Resistance to Tyrosine Kinase Inhibitors”. The presentation reviewed previously disclosed preclinical data including:
- An overview of KTN0158’s unique mechanism of action which inhibits KIT activation by blocking receptor dimerization; and
- The preclinical activity of KTN0158 in GIST models with activating KIT mutations and also activity in dogs with spontaneous mast cell tumors driven by KIT activation.
On Tuesday, April 19, “Inhibition of KIT In Vivo Modifies Immune Cell Populations to Improve the Efficacy of Checkpoint Inhibitors in Syngeneic Mouse Tumor Models” (Abstract Number 4020), was presented in a poster session.
The poster presentation reported the following data and results:
- Enhanced anti-tumor activity with the combination of a surrogate mouse anti-KIT monoclonal antibody with either anti-PD-1 or anti-CTLA4 monoclonal antibodies in several syngeneic mouse tumor models; and
- Mechanistic studies showed a significant decrease in monocytic myeloid-derived suppressor cells (mMDSCs) in the tumor and in the spleen of the anti-KIT antibody treated groups. High levels of circulating mMDSCs have been associated with reduced survival in melanoma patients treated with ipilimumab or nivolumab.
The poster is available on the Kolltan website.
About KTN0158
KTN0158 is a proprietary, humanized monoclonal antibody designed using structure-based approaches to block the activation of KIT, an RTK that is expressed on many cancers and mast cells. There are currently no KIT-targeting antibodies on the market for any disease indication. In oncology, KIT is expressed in tumors such as GIST, melanoma, acute myeloid leukemia (AML), small cell lung cancer (SCLC), and others. Additionally, KIT is expressed in immune suppressive cells in the tumor microenvironment and thus may provide a novel combination treatment for immuno-oncology. Kolltan has initiated a Phase 1 study for the treatment of GIST and other KIT-expressing tumors (NCT02642016) and plans to move into combination studies with other targeted therapies and T cell checkpoint inhibitors.
About Kolltan Pharmaceuticals
Kolltan, a privately held clinical-stage company, is focused on the discovery and development of novel, antibody-based drugs targeting RTKs for the treatment of cancer and other diseases with significant unmet need. Kolltan’s founders and members of its management team have deep expertise and a proven track record in drug discovery, development, and commercialization of innovative therapeutics, including drugs targeting RTKs. Kolltan is working in close collaboration with the laboratory of Kolltan Co-Founder, Dr. Joseph Schlessinger, as well as the Yale University medical and scientific community. The Company has a broad and novel oncology and immunology portfolio of therapeutic biologics targeting multiple RTKs that are advancing in the clinic and are expected to generate multiple near-term milestones.
SOURCE: Kolltan Pharmaceuticals
Post Views: 133
