Kymera Therapeutics Presents Positive Preclinical Data on Selective STAT3 Degraders for Hematological and Solid Tumor Malignancies at 63rd American Society of Hematology (ASH) Annual Meeting

Rhea-AI Summary

Kymera Therapeutics (NASDAQ: KYMR) presented promising preclinical data on its first-in-class STAT3 degrader, KT-333, at the 63rd American Society of Hematology Annual Meeting. KT-333 demonstrated over 90% STAT3 knockdown in ALK+ anaplastic large cell lymphoma (ALCL) models, leading to significant tumor regression. The studies suggest the potential for KT-333 in combination with immune checkpoint inhibitors in solid tumors. A Phase 1 trial is set to start, focusing on hematologic and solid cancers. The findings may help identify patients likely to respond to STAT3 degraders.

Positive

• KT-333 induced >90% STAT3 knockdown and tumor regression in ALCL models.
• Demonstrated potential for combination therapy with anti-PD1 antibodies in solid tumors.
• Upcoming Phase 1 trial aims to explore KT-333's efficacy in hematologic and solid tumors.

Negative

• None.

Two presentations demonstrated Kymera’s STAT3 degraders can reduce STAT3 expression, modify STAT3-dependent signaling, and suppress the growth of tumors in multiple preclinical models of lymphoma and solid tumors

WATERTOWN, Mass., Dec. 13, 2021 (GLOBE NEWSWIRE) -- 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
  

About Kymera Therapeutics 
Kymera Therapeutics (Nasdaq: KYMR) is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Kymera’s Pegasus™ platform enables the discovery of novel small molecule degraders designed to harness the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on undrugged nodes in validated pathways currently inaccessible with conventional therapeutics. Kymera’s initial programs are IRAK4, IRAKIMiD, and STAT3, each of which addresses high impact targets within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Kymera’s goal is to be a fully integrated biopharmaceutical company at the forefront of this new class of protein degrader medicines, with a pipeline of novel degrader medicines targeting disease-causing proteins that were previously intractable. 

Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by FierceBiotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn. 

Cautionary Note Regarding Forward-Looking Statements 
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding its: strategy, business plans and objectives for the STAT3 degrader program; and plans and timelines for the clinical development of Kymera Therapeutics' product candidates, including the therapeutic potential and clinical benefits thereof. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of COVID-19 on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our current preclinical studies and future clinical trials, strategy and future operations; the delay of any current preclinical studies or future clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies may not be predictive of future results in connection with future clinical trials; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Company’s planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Quarterly Report on Form 10-Q for the period ended September 30, 2021, filed on November 10, 2021, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. 

Investor Contact: 
Bruce Jacobs  
Chief Financial Officer  
investors@kymeratx.com 
857-285-5300 

Chris Brinzey 
Managing Director, Westwicke 
chris.brinzey@westwicke.com 
339-970-2843 

Media Contact: 
Tyler Gagnon 
Director, Corporate Communications 
tgagnon@kymeratx.com  
508-904-9446

FAQ

What are the key findings from Kymera Therapeutics' KT-333 presentations at the ASH Annual Meeting?

Kymera's KT-333 showed over 90% STAT3 knockdown and induced tumor regressions in ALCL models, highlighting its therapeutic potential.

When is Kymera Therapeutics starting the Phase 1 trial for KT-333?

The Phase 1 trial for KT-333 is set to initiate soon, focusing on both hematologic and solid tumors.

What does KT-333 target in cancer treatment?

KT-333 targets the STAT3 protein, which is implicated in various hematologic and solid cancers, aiming to degrade it for therapeutic benefits.

How might KT-333 work in combination with other therapies?

KT-333 may enhance the effectiveness of immune checkpoint inhibitors, such as anti-PD1 antibodies, in treating solid tumors.

What is the significance of the preclinical results presented by Kymera?

The preclinical results indicate KT-333's potential as a viable treatment option for previously difficult-to-treat cancers, paving the way for patient selection based on gene expression signatures.