Kymera Therapeutics Announces Updated Clinical Data from the Phase 1 Trials of STAT3 Degrader KT-333 and IRAKIMiD Degrader KT-413

Data shared today in abstracts from the International Conference on Malignant Lymphoma (ICML)

Both programs continue to demonstrate substantial target knockdown in ongoing clinical trials, with no dose limiting toxicities observed

Data on additional KT-333 and KT-413 patient cohorts to be shared in conjunction with
next week’s ICML meeting

WATERTOWN, Mass., June 09, 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 announced new data demonstrating that its oncology programs KT-333 and KT-413 continue to demonstrate substantial target knockdown in ongoing Phase 1a dose escalation clinical trials, with no dose limiting toxicities (DLTs) observed. The data were shared in the online abstract book of the International Conference on Malignant Lymphoma (ICML), taking place from June 13-17, 2023, in Lugano, Switzerland, and reflect a data cut-off date of February 3, 2023. On June 14, a KT-333 poster will be released at ICML and presented on June 16. Kymera will share updated results from both programs in conjunction with the poster release on June 14.

Highlights of the KT-333 Abstract

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, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of KT-333 dosed weekly in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors. 

As of the abstract cut-off date of February 3, 2023, 7 patients had been treated in the first 2 dose levels (DL1 and DL2) of the trial, including patients with solid tumors as well as peripheral T-cell lymphoma and cutaneous T-cell lymphoma:

• Plasma PK results were in line with the modeled predictions.
• PD data in peripheral blood mononuclear cells (PBMC) demonstrated dose-dependent and sustained STAT3 degradation after dosing on Days 1 and 8, with mean maximum decrease of 66% in DL1 and 70% in DL2.
• The most common adverse events were Grade 1 and 2 and included constipation, fatigue, abdominal pain, dizziness, and nausea. No DLTs were observed and no patients discontinued KT-333 due to an adverse event.
• Accrual into the study is ongoing, and analyses from additional patients will be presented at ICML.

As previously announced, Kymera intends to present data evaluating anti-tumor activity in the target patient population later this year.

KT-333 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

Highlights of the KT-413 Abstract

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 intravenous infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas.

As of the abstract cut-off date of February 3, 2023, 3 patients had been treated in the first 3 dose levels of the trial, including transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma and marginal zone lymphoma, all of which were MYD88 wild-type:

• Plasma PK results were in line with the modeled predictions.
• Dose-dependent, sustained target knockdown in PBMC was observed, with up to 57% reduction in IRAK4 and 96-100% reduction in Ikaros and Aiolos by DL3. Degradation was also demonstrated in serial tumor biopsies obtained in DL1.  
• The most common adverse events across all three dose levels were Grade 1 and 2 fatigue and pyrexia. No DLTs were observed.
• Accrual into the study is ongoing, and analyses from additional patients will be shared in an update from Kymera in conjunction with the KT-333 ICML update.

As previously announced, Kymera intends to present data evaluating anti-tumor activity in the target patient population later this year.

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, 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.