NEW HAVEN, CT, USA I November 6, 2015 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), today announced the presentation of preclinical data showing that KTN3379 reverses ErbB3-mediated resistance of BRAF and MEK inhibitors in BRAF-mutated thyroid cancer and melanoma. KTN3379 is a potent, human anti-ErbB3 (HER3) monoclonal antibody drug candidate in Phase 1b clinical trials being developed for the treatment of adult patients with various solid tumors.
The preclinical results will be presented in a poster titled, “KTN3379 overcomes ErbB3-mediated resistance of BRAF/MEK inhibition in BRAF-mutated melanoma” (Abstract # A154, Therapeutic Agents: Biological, on Friday, November 6, 2015, 12:15pm to 3:15pm EST, Poster Session A). The conference is being held November 5- 9 in Boston, Massachusetts.
“These compelling preclinical data, as well as recently reported antitumor activity in the BRAF treatment arm of the Company’s ongoing Phase 1b clinical study, support further clinical studies in BRAF-mutant tumors, including our recently initiated Phase 1b study in BRAF mutated thyroid cancers,” stated Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan. “This new strategy complements our ongoing program that is investigating the potential of KTN3379 to reduce ErbB3-driven growth with HER2 and EGFR blockers, providing multiple ways to bring KTN3379 to cancer patients.”
“We are excited about these new data and what they tell us about the potential for KTN3379 to enhance the benefits of BRAF and MEK inhibitors in BRAF-mutated tumors. Our clinical development strategy is pursuing different combinations with targeted therapies in cancer patients where ErbB3 plays a role including tumors where genetic alterations such as BRAF are present,” said Theresa LaVallee, Ph.D., Senior Vice President Translational Medicine and Product Development of Kolltan Pharmaceuticals.
The poster presentation will include the following data and results:
- Targeting ErbB3 with KTN3379 hampers adaptive resistance in tumors when BRAF and MEK inhibitors are used to block MAPK signaling;
- ErbB3 is upregulated in response to BRAF and MEK inhibition;
- Neuregulin (NRG) -stimulates activation of ErbB3 and AKT is increased in a dose-dependent manner when BRAF mutant tumor cells are treated with trametinib or vemurafenib;
- NRG reduces the antiproliferative effects of BRAF and MEK inhibitors, however treatment with KTN3379 resensitized the tumor cells to inhibitors;
- Tumors with a high prevalence of activating BRAF mutations express NRG1 and/or NRG2, which may provide autocrine stimulation of ErbB3 and contribute to adaptive resistance;
- NRG1β was found to be the most potent ErbB3 ligand tested; and
- Ongoing Phase 1b studies combining KTN3379 with vemurafenib in BRAF-mutated tumors support further clinical trials with patients with tumors having BRAF mutations
About KTN3379
KTN3379 is a human monoclonal antibody designed to block the activity of ErbB3, a receptor tyrosine kinase (RTK) that belongs to the epidermal growth factor receptor, or EGFR, family. ErbB3 is believed to be an important receptor regulating cancer cell growth and survival. ErbB3 is expressed in many cancers, including head and neck, breast, lung, gastric, and melanoma. While there are several successful currently marketed products targeting two members of the EGFR family, there are none that directly target ErbB3. In cancer, ErbB3 activation can be driven by its ligand, neuregulin, or in its absence, through overexpression of its co-receptor ErbB2 (HER2).
Kolltan is conducting multiple clinical trials evaluating KTN3379 in the treatment of solid tumors. These trials include an ongoing Phase 1b multi-center, open-label, dose escalation clinical trial of KTN3379 in patients with solid tumors, with expansion cohorts testing KTN3379 in combination with cetuximab, erlotinib, vemurafenib, or trastuzumab. In addition, the Company is conducting a Phase 1b study in thyroid cancer, evaluating the treatment of patients with radioactive iodine refractory BRAF-mutated cancers with a combination of KTN3379 and vemurafenib. A third clinical study is evaluating tissue responses to KTN3379 in newly diagnosed patients with head and neck cancers who are treated with KTN3379 prior to their surgical resection.
About Kolltan Pharmaceuticals
Kolltan, a privately held clinical-stage company, is focused on the discovery and development of novel, best-in-class antibody-based drugs targeting receptor tyrosine kinases 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 kinases. 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 portfolio of therapeutic biologics targeting multiple receptor tyrosine kinases that are advancing in clinical and preclinical development and are progressing toward potential achievement of multiple near-term milestones. Kolltan’s most advanced product candidates include KTN3379, a human monoclonal antibody designed to block the activity of ErbB3 which is in Phase 1b clinical trials in solid tumors, and KTN0158, a humanized monoclonal antibody designed to block the activation of KIT which is anticipated to enter clinical trials in early 2016.
SOURCE: Kolltan Pharmaceuticals
