Kolltan Pharmaceuticals Presents Preclinical Data at the 2016 American Association for Cancer Research (AACR) Annual Meeting
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 KTN3379 and KTN0073 drug development programs at the AACR Annual Meeting, taking place in New Orleans, Louisiana, April 16-20, 2016.
"This new preclinical data with KTN3379, along with emerging clinical results to date, support our plans to initiate a Phase 2 study in squamous cell tumors of the head and neck. Separately, we have identified KTN0073 as a unique antibody targeting the Met receptor tyrosine kinase with novel mechanisms of action. We are actively seeking a partner for the KTN0073 program to assist in the development of this novel and differentiated antibody drug candidate," stated Gerald McMahon, Ph.D., President and Chief Executive Officer of Kolltan.
"KTN3379 has shown broad anti-tumor activity in preclinical models, is potent, and binds to a unique epitope on ErbB3 or HER3. We presented scientific data supporting the potential use of KTN3379 for treatment of squamous cell tumors of the head and neck (HNSCC) and we continue to explore additional tumor indications where ErbB3 plays a role in driving the tumor or limiting therapies due to pathway resistance. The data presented shows anti-tumor activity of KTN3379 in HNSCC models in combination with the standard of care, cetuximab and radiation, and the anti-tumor activity correlated with several measurable parameters related to activation of the ErbB3 or EGF receptors. HNSCC cancer enriches for these parameters, and we are measuring these endpoints in ongoing and future clinical studies to guide patient selection and drug effectiveness," said Theresa LaVallee, Ph.D., Senior Vice President, Translational Medicine and Product Development at Kolltan.
Following are key data and results from the four poster presentations at AACR relating to KTN3379 and KTN0073:
KTN3379 is an IgG1 monoclonal antibody that effectively locks ErbB3 in an inactive conformation by binding to a unique epitope, which may contribute to the antibody's high potency and dual mechanism of action.
On Monday, April 18, "Combination of neuregulin with EGFR activation signatures predict activity of the anti-ErbB3 antibody KTN3379 in SCCHN" (Abstract Number 1196) was presented in a poster session.
The poster presentation reported the following data and results:
- ErbB3 and its ligand neuregulin (NRG) are highly expressed in HNSCC and HER2, not EGFR, catalyzes ErbB3 activation in the presence of NRG;
- Database analyses of HNSCC patient samples indicated that NRG expression is highly correlated with the expression of the EGFR ligands amphiregulin (AREG) and transforming growth factor α (TGFα), but not other EGFR ligands;
- Using NRG-positive cell lines, KTN3379 anti-tumor activity correlated with the level of secreted AREG and TGFα and EGFR homodimer levels; and
- The combined measurement of NRG with EGFR activation is a potential biomarker for KTN3379 activity.
On Tuesday, April 19, "Dual targeting of HER3 and PIK3CA has potent anti-tumor effects in pre-clinical models of HNSCC" (Abstract Number 2979) was presented in a poster session.
The poster presentation featured the following data and results:
- Combined administration of KTN3379 and BYL719, a PIK3Cα inhibitor, enhanced anti-tumor activity over single agent administration in HNSCC models;
- Inhibition of PI3K led to upregulation of ErbB3 activity;
- ErbB3 upregulation attenuated PI3K inhibition suggesting ErbB3 is playing a role in resistance as a compensatory pathway; and
- Dual targeting of the ErbB3 and PI3K pathways led to synergistic anti-tumor activity in vitro and in vivo.
On Tuesday, April 19, "Inhibition of heregulin-mediated ErbB3 signaling as a radiosensitization therapy for head and neck cancers" (Abstract Number 3053) was presented in a poster session.
The poster presentation reported the following data and results:
- Two different HNSCC models of cetuximab resistance were generated using A431 and FaDu cell lines by exposure to increasing doses of cetuximab over 14 weeks;
- In these models, ErbB3 levels and signaling were upregulated and KTN3379 effectively blocked elevated ErbB3 signaling and overcame the cetuximab resistance in the A431 and FaDu models;
- In a panel of six HNSCC cell lines, KTN3379 enhanced the anti-tumor activity of radiation alone or the combination of radiation and cetuximab in most of the cell lines; and
- These results suggest that combining KTN3379 with standard of care treatments in HNSCC, including cetuximab and radiation, may enhance anti-tumor activity and may overcome resistance.
KTN0073 is a humanized, IgG2 monoclonal antibody that inhibits Met-dependent tumor growth in preclinical models when activated by HGF, Met gene amplification, or mutations in exon 14.
On Tuesday, April 19, "An anti-Met IgG2 monoclonal antibody degrades both wild-type and exon 14 mutant MET receptor tyrosine kinase through a novel exon 14-independent mechanism and inhibits tumor growth" (Abstract Number 3835) was presented in a poster session.
The poster presentation highlighted the following data and results:
- KTN0073 was identified as a potent anti-Met antibody with broad anti-tumor activity in HGF-driven and Met amplified tumors;
- KTN0073 induced potent degradation of oncogenic exon 14-mutant Met, which propagates prolonged Met signaling due to a defect in receptor degradation;
- Conversion of the antibody from IgG1 to IgG2 surprisingly resulted in enhanced anti-tumor activity in vitro and in vivo; and
- KTN0073 demonstrated broad anti-tumor activity through multiple mechanisms of action in HGF-driven, Met-amplified, and exon 14-mutated tumors.
The posters are available on the Kolltan website.
KTN3379 is a human monoclonal antibody designed to block the activity of ErbB3 (HER3), 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. Kolltan is conducting multiple clinical trials evaluating KTN3379 in the treatment of solid tumors (NCT02014909, NCT02456701, and NCT02473731).
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.
Forward Looking Statements Disclosure
Any statements in this news release about future expectations, plans, and prospects for Kolltan constitute forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of a variety of important factors. Kolltan anticipates that subsequent events and developments may cause its views to change. However, while Kolltan may elect to update these forward-looking statements in the future, Kolltan specifically disclaims any obligation to do so.