Data demonstrate Kymera’s ability to degrade mutant and wild-type STAT3, a traditionally “undruggable” target, and the broad therapeutic potential for the treatment of peripheral T-cell lymphoma subtypes with aberrant STAT3 activation
Kymera anticipates IND submission for STAT3 degrader KT-333 in 4Q 2021, and if cleared, initiation of Phase 1 trial in liquid and solid tumors
WATERTOWN, Mass., July 12, 2021 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation to deliver novel small molecule protein degrader medicines, today announced new preclinical data demonstrating the therapeutic potential of its STAT3 degraders for the treatment of peripheral T-cell lymphoma (PTCL) with aberrant STAT3 activation. The data were featured in a presentation at the virtual 13th Annual T-Cell Lymphoma Forum, taking place from July 8 - 10, 2021 (Abstract 11: Targeting STAT3 with Selective Protein Degraders for the Treatment of PTCL).
Kymera is developing selective STAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune diseases and fibrosis. STAT3 is a transcription factor activated through a variety of different cytokine and growth factor receptors via Janus kinases (JAKs), as well as through oncogenic fusion proteins and mutations in STAT3 itself. Long considered an “undruggable” target, STAT3 hyperactivation is prominent in numerous liquid and solid tumors, including clinically aggressive lymphomas. Kymera’s STAT3 degraders have been shown to strongly repress cancer cell growth in preclinical models of STAT3-dependent heme malignancies, including subtypes of PTCL such as ALK-positive anaplastic large cell lymphoma (ALCL). Kymera’s lead STAT3 degrader candidate, KT-333, is currently in preclinical development and Kymera plans to submit an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2021 and, if cleared, initiate a Phase 1 clinical trial in patients thereafter.
“The activity of the STAT3 transcription factor is dysregulated in many cancers, including aggressive hematological malignancies with high unmet medical need,” said Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. “We have demonstrated that our potent and selective STAT3 degraders are able to achieve greater than 90% degradation of mutant as well as wild-type STAT3, resulting in downregulation of STAT3-dependent genes and broad antitumor activity across both T-cell and NK/T-cell subtypes of PTCL. We look forward to completing the preclinical development of KT-333 and filing an IND later this year to enable subsequent initiation of a Phase 1 trial in liquid and solid tumors.”
Data highlights include:
- Kymera has discovered a series of potent and selective STAT3 degraders with activity against both wild-type and clinically-relevant mutant forms of STAT3.
- STAT3 degraders result in growth arrest and increased cell death of ALK-positive ALCL, as well as STAT3-mutant NK/T-cell lymphoma and ALK-negative ALCL cell lines, both in vitro and in vivo, including complete tumor regressions in vivo in ALK-positive ALCL with IV weekly dosing.
- Pathway analyses in STAT3 degrader-treated ALK-positive ALCL show down-regulation of STAT3-regulated processes including cytokine responses and consistent down-regulation of cell cycle signatures and up-regulation of immune pathways, suggesting modulation of tumor cell-intrinsic processes and the potential to regulate cell-cell interactions in the tumor microenvironment.
- A subset of transcriptional responses to STAT3 degrader is conserved between ALK-positive ALCL and STAT3 mutant NK/T-cell lymphoma cell lines.
- Title: Targeting STAT3 with Selective Protein Degraders for the Treatment of PTCL
- Session VI: Poster Presentations
- Session Time: 6:30 p.m. – 7:35 p.m. ET on Friday, July 9, 2021
- Abstract: 11
- Presenter: Philip C.C. Liu, Ph.D.
A copy of the poster presentation is available for download at https://investors.kymeratx.com/events-and-presentations and https://www.kymeratx.com/scientific-resources/.
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.
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 by Kymera Therapeutics 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 Kymera Therapeutics has operations or does business, as well as on the timing and anticipated results of its 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 Kymera Therapeutics’ 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 March 31, 2021, filed on May 6, 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.
VP, Investor Relations and Communications
Lissette L. Steele
Verge Scientific Communications for Kymera Therapeutics