Kymera Therapeutics to Present New Clinical Data from Ongoing Phase 1 Trial of MDM2 Degrader KT-253 at ASCO Annual Meeting

Abstract released today highlights safety, pharmacodynamic and clinical response data with additional data to be presented in a poster session on June 1, 2024

KT-253 Phase 1 study ongoing with additional data expected in the second half of 2024

WATERTOWN, Mass., May 23, 2024 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new class of small molecule medicines using targeted protein degradation (TPD), today announced new clinical data for KT-253, a first-in-class MDM2 degrader, from its ongoing Phase 1 dose escalation trial will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place from May 31 – June 4, 2024, in Chicago, Illinois. Results released in an ASCO abstract today include a data cut-off of January 26, 2024.

“We continue to see encouraging data from the trial’s dose escalation phase demonstrating potent upregulation of p53 biomarkers and signs of antitumor activity in patients. Results have included objective responses in liquid and solid tumors, at doses that are well tolerated without the traditional hematological toxicity seen with small molecule inhibitors,” said Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics. “We look forward to sharing the full Phase 1 data set, as well as our biomarker-based patient selection strategy and guidance on the program’s next development steps, later this year.”

Highlights of the KT-253 Clinical Abstract

The abstract reported Phase 1 data from 18 patients including 13 patients in Arm A (solid tumors and lymphomas) at dose levels (DL) 1-4, and 5 patients in Arm B (high grade myeloid malignancies) at DL1-2 as of January 26, 2024. The most common solid tumor types were Merkel cell carcinoma (MCC) in 3 patients, adenoid cystic carcinoma (ACC) in 2 patients, and uveal melanoma in 2 patients. Highlights include:

• Disease Response Assessments:
  • Arm A: One partial response confirmed in a MCC patient in DL1. Additionally, 3 stable diseases were reported for patients with fibromyxoid sarcoma, ACC, and renal cell cancer in DL1-3, respectively.
  • Arm B: One confirmed complete response in DL2 and one confirmed partial response in DL1, both in patients with post-myeloproliferative neoplasm (MPN) acute myeloid leukemia (AML). 
• Pharmacodynamic (PD) data from Arm A (DL1-4) and Arm B (DL1-2) demonstrated rapid upregulation of plasma GDF-15 protein and upregulation of CDKN1A and PHLDA3 mRNA levels in blood. KT-253 demonstrated dose-dependent increase in plasma exposure with levels approximating projected efficacious doses.
• KT-253 was generally well-tolerated with the most common adverse events (AEs) including nausea, fatigue, headache, and vomiting. There was 1 dose-limiting toxicity (DLT) of AEs leading to discontinuation that included Grade 2 nausea and fatigue in Arm A DL4. There were no neutropenia or thrombocytopenia AEs in either Arm. KT-253 related serious adverse events (SAEs) included Grade 3 hypotension in a patient with decreased oral intake in Arm A DL1.
  

The poster to be presented will include three additional patients in each Arm, as well as pharmacokinetic, pharmacodynamic, and safety data subsequent to the abstract cut-off date. A copy of the poster will be available on June 1, 2024, in the Resource Library section of Kymera’s website.

The Phase 1a trial for KT-253 is currently ongoing. The Company expects to complete the study and share additional clinical data to inform the program’s next development steps in 2024 at an upcoming medical meeting. Kymera is also developing a biomarker-based patient selection strategy for subsequent development beyond Phase 1a and is expected to present data at a medical meeting this year.

Poster Presentation at ASCO

Title: Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Efficacy of KT-253, a Targeted Protein Degrader of MDM2, in Patients with Relapsed/Refractory (R/R) Solid Tumors, Lymphoma, High Grade Myeloid Malignancies and Acute Lymphoblastic Leukemia (ALL)
Abstract ID Number: 3084
Session Date/Time: June 1, 2024, from 9:00 AM – 12:00 PM CT
Presenter: Muhammad R. Khawaja, MD, HonorHealth Research Institute, Scottsdale, AZ

About KT-253 MDM2 Degrader
KT-253 targets MDM2, the crucial regulator of the most common tumor suppressor, p53. P53 remains intact (wild type) in close to 50% of cancers, meaning that it retains its ability to modulate cancer cell growth. While small molecule inhibitors (SMIs) have been developed to stabilize and upregulate p53 expression, they have been unable to show meaningful clinical benefits of p53 stabilization, with acceptable safety margins, likely due to their inability to overcome a feedback loop that increases MDM2 protein levels when p53 is upregulated. In preclinical studies, KT-253 has shown the ability to overcome the MDM2 feedback loop and rapidly induce cancer cell death with brief exposures, providing the opportunity for an improved efficacy and safety profile. The Phase 1 study of KT-253 will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and clinical activity of KT-253 in patients with relapsed or refractory high grade myeloid malignancies, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), lymphomas, and solid tumors. KT-253 has achieved clinical proof-of-mechanism in the Phase 1 trial and shown early signs of anti-tumor activity and the Phase 1a trial is currently ongoing.

About Kymera Therapeutics
Kymera is a clinical-stage biotechnology company pioneering the field of targeted protein degradation (TPD) to develop medicines that address critical health problems and have the potential to dramatically improve patients’ lives. Kymera is deploying TPD to address disease targets and pathways inaccessible with conventional therapeutics. Having advanced the first degrader into the clinic for immunological diseases, Kymera is focused on delivering oral small molecule degraders to provide a new generation of convenient, highly effective therapies for patients with these conditions. Kymera is also progressing degrader oncology programs that target undrugged or poorly drugged proteins to create new ways to fight cancer. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces for the past several years. For more information about our science, pipeline and people, please visit www.kymeratx.com or follow us on X (previously 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 its clinical 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 ability to initiate new clinical programs; and Kymera's financial condition and expected cash runway into the first half of 2027. 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 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 for 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; the risks associated with pandemics or epidemics; 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 Annual Report on Form 10-K for the period ended December 31, 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.