Kymera Therapeutics to Present Preclinical Data Demonstrating the Potency and Antitumor Activity of a Selective STAT3 Degrader at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
CAMBRIDGE, Mass., Oct. 17, 2019 /PRNewswire/ -- Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, today announced the company will present preclinical data showing the discovery and characterization of novel, selective, and potent degraders of STAT3, a transcriptional regulator linked to numerous cancers and other diseases. Data will be shared during a poster presentation (Abstract #C054) at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston on Tuesday, October 29 at 12:30 PM EST.
STAT3 is an oncogenic transcription factor that is regulated by multiple signaling events including the IL-6-JAK pathway and growth factor receptors. Activating mutations and aberrant activation of STAT3 have been directly linked to the promotion of cancer cell survival and proliferation and immune evasion, making it a highly attractive target for hematologic malignancies and solid tumors.
"STAT3 has historically been considered an 'undruggable' transcription factor. Over the past few decades, some of the key challenges for this target have been the lack of small molecule binders, additional functions beyond transcriptional regulation, and sequence homology with other SH2 domain-containing STAT family members," said Nello Mainolfi, PhD, Founder, President & CSO of Kymera Therapeutics. "Using our drug discovery engine, especially our understanding of ternary complex structure and function, we rationally designed specific STAT3 degraders with excellent in vivo properties. Our data using these degraders have shown disruption of signaling downstream of STAT3 and promising antitumor activity in multiple cancer models, supporting the transformative therapeutic potential of this modality. With these unique molecules we are expanding the understanding of the biological impact of STAT3 degradation in tumor and immune contexts."
AACR-NCI-EORTC Study Highlights
ABSTRACT #C054, "Discovery of KYM-003, a Potent and Selective STAT3 Degrader with Anti-Tumor Activity in Heme Malignancies," presented by Fred Csibi, Associate Director, Oncology Biology at Kymera Therapeutics.
in vitro
- KYM-003 cooperatively formed a high-affinity STAT3-KYM003-E3 ligase ternary complex.
- KYM-003 potently induced ubiquitination of endogenous STAT3.
- KYM003-induced degradation was highly selective for STAT3 versus >10,000 other detected proteins (including all other STAT family members) in tumor cell lines and hPBMCs.
- KYM003-induced degradation of STAT3 resulted in downregulation of STAT3 target-gene expression, including the PIM1 oncogene.
in vivo
- Total STAT3 levels in tumors were reduced by >90% for at least 24 hours after a single dose of KYM-003.
- Repeated dosing of KYM-003 showed dose-dependent antitumor activity in xenograft models of heme malignancies with good tolerability.
About Kymera Therapeutics
Kymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body's innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by Pegasus™, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, www.kymeratx.com.
About Pegasus™
Pegasus™ is Kymera Therapeutics' proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities, and degradation tools.
SOURCE Kymera Therapeutics Inc.
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