Data shared today on PK/PD and safety from additional KT-333 and KT-413 patient dose escalation cohorts show target knockdown at or near levels associated with clinical efficacy in preclinical tumor models
No dose limiting toxicities observed in either program
KT-333 data will be presented in a poster session at the International Conference on Malignant Lymphoma (ICML) on June 16
WATERTOWN, Mass., June 14, 2023 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today shared new data demonstrating that its oncology programs KT-333 and KT-413 continue to demonstrate robust dose-dependent target knockdown in ongoing Phase 1a dose escalation clinical trials, with no dose limiting toxicities (DLTs) observed. The KT-333 clinical data will be presented in a poster at the International Conference on Malignant Lymphoma (ICML) on June 16, 2023, in Lugano, Switzerland.
“Our focus this year for our ongoing KT-333 and KT-413 clinical trials will be to analyze the degradation profiles and safety of these first-in-class mechanisms and evaluate their biological and clinical impact in the appropriate patient populations. We continue to see encouraging data from the trials’ dose escalation phases as they show fidelity of PK/PD translation from preclinical models to patients, demonstrating target degradation without any dose limiting toxicities observed, and approaching levels we believe are needed to achieve antitumor activity,” said Nello Mainolfi, Founder, President and CEO, Kymera Therapeutics. “We are proud and excited to be the first company to have shown clinical translation of our degraders’ profiles across three programs and across multiple diseases and indications. We look forward to sharing additional data evaluating antitumor activity in the target patient populations for these programs later this year.”
KT-333 STAT3 Program
KT-333 is designed as a potent degrader of STAT3, a transcriptional regulator that has been linked to numerous cancers as well as to inflammatory and autoimmune diseases. KT-333 is being developed for the treatment of STAT3-dependent hematological malignancies and solid tumors. The Phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-333 dosed weekly on 28-day cycles in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors.
As of the data cut-off of May 1, 2023, thirteen patients received a mean of five doses across the first four dose levels (DL1-4) of the trial, including patients with solid tumors as well as peripheral and cutaneous T-cell lymphoma. This includes 2 patients enrolled in DL4, which remains open to accrual. As of the cut-off date, there were no AEs reported in DL4. Data reported from the 3 completed dose levels (DL1-3) found:
- Plasma exposure increased with dose, reaching levels close to those predicted to be efficacious.
- KT-333 demonstrated dose-dependent STAT3 degradation with up to 88% mean maximum reduction in peripheral blood mononuclear cells (PBMCs), with evidence of STAT3 pathway inhibition and downregulation of inflammatory biomarkers in peripheral blood. Degradation profiles at DL-3 were near levels of knockdown that led to profound antitumor activity in preclinical models.
- No DLTs were observed in the study.
KT-333 Poster Presentation at ICML
Title: Phase 1 Trial of KT-333, a STAT3 Degrader, in Patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia and Solid Tumors
Presentation ID: 424
Session Time: 12:30 p.m. - 1:00 p.m. CEST, June 16, 2023
Location: Marquee Parco Ciani
Presenter: Dr. Adam Olszewski, Lifespan Cancer Institute, Rhode Island Hospital
KT-413 IRAKIMiD Program
KT-413 is a novel heterobifunctional degrader targeting both IRAK4 and the IMiD substrates Ikaros and Aiolos. Designed to address both the IL-1R/TLR and Type 1 IFN pathways synergistically with a single molecule, KT-413 is in development for the treatment of MYD88-mutant B-cell malignancies. The Phase 1 clinical trial of KT-413 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-413 administered as an IV infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas.
As of the data cut-off of June 1, 2023, DL1-3 have been completed and DL4 remains open to accrual. Five patients were treated across DL1-4 and received a mean of 2.2 doses. These included patients with transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma, and plasmablastic lymphoma, all of whom were MYD88 wild-type except for one who had a MYD88 gain-of-function mutation. Data reported across the 4 DLs through the cut-off date show:
- Plasma exposure increased with dose, reaching levels close to those predicted to be efficacious.
- KT-413 achieved dose-dependent degradation of up to 70% IRAK4 and 96-100% Ikaros and Aiolos in PBMC after a single dose. Degradation profiles at DL3-4 were consistent with knockdown levels associated with profound antitumor activity in preclinical models of MYD88 mutant lymphomas.
- No DLTs or drug-related neutropenia were observed in the study.
About Kymera Therapeutics
Kymera is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule programs designed to harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutic candidates designed to address the most promising targets and provide patients with more effective treatments. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” company by Fierce Biotech and has been recognized by both the Boston Globe and the Boston Business Journal as one of Boston’s top workplaces. 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 IRAKIMiD and STAT3 degrader programs; plans and timelines for the preclinical and clinical development of its product candidates, including the therapeutic potential, clinical benefits and safety thereof; expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials. 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 and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical and clinical trials, including those for KT-474, KT-333, KT-413 and KT-253; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Kymera Therapeutics' planned interactions with regulatory authorities; obtaining, maintaining and protecting its intellectual property; and Kymera Therapeutics' relationships with its existing and future collaboration partners. 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 quarter ended March 31, 2023 filed on May 4, 2023, 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.
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