Kymera Therapeutics, Inc. (NASDAQ:KYMR), a biopharmaceutical company advancing targeted protein degradation to deliver novel, small molecule protein degrader therapeutics, today announced the company presented new
Kymera Therapeutics, Inc. (NASDAQ:KYMR), a biopharmaceutical company advancing targeted protein degradation to deliver novel, small molecule protein degrader therapeutics, today announced the company presented new preclinical data for its STAT3 degraders, including its first-in-class KT-333 STAT3 degrader, at the virtual 63rd American Society of Hematology (ASH) Annual Meeting taking place from December 11 – 14, 2021 in Atlanta, GA and virtually.
Kymera's first presentation, "A First-in-Class STAT3 Degrader KT-333 in Development for Treatment of Hematologic Cancers" showcased how its clinical compound KT-333 induced growth arrest and cell death in multiple models of anaplastic large cell lymphoma (ALCL). This resulted in eradication of ALK+ ALCL tumor xenografts with weekly or every other week dosing associated with >90% STAT3 knockdown in tumors and modulation of STAT3-dependent signaling. In addition, KT-333 reduced mediators of immune suppression in an ex vivo, co-culture model of the tumor microenvironment in non-small cell lung cancer and led to tumor regressions in the mouse CT-26 colorectal cancer syngeneic tumor model when coupled with an anti-PD1 antibody, demonstrating the potential for this combination immunodulatory approach in solid tumors.
"KT-333 is a potent and selective STAT3 degrader targeting a high priority, previously undruggable transcription factor that has the potential to address a range of hematologic and solid cancers based on a growing body of preclinical studies described to date," said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. "We are excited about the development opportunities as a monotherapy in STAT3-dependent T and NK cell hematologic malignancies and in combination with immune checkpoint inhibitors in solid tumors as we are about to initiate our Phase 1 trial in liquid and solid tumors."
The second presentation, "Selective STAT3 Degraders Dissect Peripheral T-Cell Lymphomas Vulnerabilities Empowering Personalized Regimens" highlights results from a research collaboration with Georgio Inghirami, MD, Weill Cornell Medical College. In primary patient-derived tumor xenograft (PDTX) models of anaplastic large cell lymphoma (ALCL), selective STAT3 degraders were shown to potently degrade STAT3 and modify STAT3-dependent signaling, leading to tumor growth inhibition and cell death in an ALK- ALCL model characterized by STAT3 activation via STAT3 and Jak1 mutations. STAT3 degraders were also shown to synergize with other targeted agents, such as venetoclax, in various peripheral T-cell lymphoma (PTCL) PDTX models.
"Taken together, these findings help to identify STAT3-dependent hematologic malignancies based on pathogenic mutations, as well as gene expression signatures, potentially enabling the selection of patients most likely to respond to STAT3 degraders," said Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics. "Our Phase 1 trial of KT-333 will further aid in defining tumor biomarkers of response to STAT3 degradation that will inform the design of subsequent trials in PTCL."
KT-333 Presentation Details:
- Title: A First-in-Class STAT3 Degrader KT-333 in Development for Treatment of Hematologic Cancers
- Poster Session: 802. Chemical Biology and Experimental Therapeutics: Poster 1
- Abstract Number: 1865
- Session Time: 5:30 p.m. – 7:30 p.m. ET on Saturday, Dec. 11, 2021
- Location: Hall B5, Georgia World Congress Center, Atlanta, GA
- Presenter: Phillip Liu, Executive Director, Oncology Biology, Kymera Therapeutics
KTX-105 and KTX-154 Presentation Details:
- Title: Selective STAT3 Degraders Dissect Peripheral T-Cell Lymphomas Vulnerabilities Empowering Personalized Regimens
- Oral Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Targets and Therapeutics
- Session Time: 6:15 p.m. – 7:45 p.m. ET on Monday, Dec. 13, 2021
- Location: B302-B303, Georgia World Congress Center, Atlanta, GA
- Presenter: Giorgio Inghirami, MD, Professor of Pathology and Laboratory Medicine, Weill Cornell Medicine