Kymera Therapeutics to Present Preclinical Data Demonstrating Potent Antitumor Activity by a Selective STAT3 Degrader in Hematologic Malignancies at the American Society of Hematology Annual Meeting
- Category: Small Molecules
- Published on Tuesday, 10 December 2019 10:45
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CAMBRIDGE, MA, USA I December 9, 2019 I Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, today announced the company will present new preclinical data showing the further characterization of novel, highly selective and potent degraders of STAT3 with activity across multiple hematologic malignancies including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), acute myelogenous leukemia (AML) and diffuse large B cell lymphoma (DLBCL). Data will be shared during a poster presentation (Abstract #3803) at the American Society of Hematology Annual Meeting in Orlando on Monday, Dec. 9 at 6:00 PM EST in Orange County Convention Center, Hall B, Level 2.
STAT3 is an oncogenic transcription factor downstream of multiple signaling events including the IL-6/JAK and ALK pathways. Activating mutations and aberrant activation of STAT3 drive a subset of tumors via induction of autocrine factors that promote tumor proliferation and survival, as well as induction of proteins that contribute to a tumor permissive microenvironment. Degrading STAT3 has been shown to disrupt downstream signaling and induce antitumor responses in STAT3-dependent hematologic malignancies.
"As Kymera advances our STAT3 degraders into the clinic, we continue to expand the characterization of the biological impact of STAT3 degradation in liquid and solid tumors including the pharmacodynamic effect required to achieve complete tumor regression in a mouse xenograft model of ALK+ ALCL," said Jared Gollob, MD, CMO of Kymera Therapeutics. "These data highlight the potential for STAT3 degraders to treat STAT3-dependent lymphomas and leukemias, and enable the rational development of a treatment regimen that maximizes the probability of success in patients. We plan to select a lead STAT3 degrader for IND-enabling studies in 2020."
ASH Study Highlights
ABSTRACT #3803, "Small Molecule-Induced, Selective STAT3 Degradation Leads to Anti-Tumor Activity in STAT3-Dependent Heme Malignancies," presented by Fred Csibi, PhD, Associate Director, Oncology Biology at Kymera Therapeutics.
- KYM-003 treatment resulted in rapid, potent and highly selective STAT3 degradation with similar activity against both mutant and wild-type STAT3.
- KYM-003 repressed the growth in vitro of multiple ALK+ ALCL cell lines as well as AML and DLBCL.
- Sustained STAT3 degradation of 90% or greater led to apoptosis induction and cancer cell death within 48hr in vitro and in vivo.
- Intermittent dosing of KYM-003 achieved complete tumor regression in an ALK+ ALCL mouse xenograft model.
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.
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