Kymera Therapeutics to Present New Clinical Data from the Ongoing Phase 1 Trial of STAT3 Degrader KT-333 at EHA Annual Meeting
Kymera Therapeutics (NASDAQ: KYMR) announced new Phase 1 data for KT-333, a STAT3 degrader, set to be presented at the European Hematology Association (EHA) Annual Meeting from June 13-16, 2024. The data cut-off date was February 6, 2024. The ongoing study involves 39 patients with various hematologic and solid tumors. Key highlights include two complete responses in classic Hodgkin's lymphoma patients, three partial responses in cutaneous T-cell lymphoma patients, and stable disease in four solid tumor patients. KT-333 achieved a maximum degradation of 97.5% in peripheral blood mononuclear cells, showing favorable immunomodulatory responses. The drug was generally well-tolerated, though two dose-limiting toxicities were observed. Kymera plans to share more data in the second half of 2024.
- KT-333 achieved maximum degradation up to 97.5% in peripheral blood mononuclear cells.
- Two complete responses observed in classic Hodgkin’s lymphoma patients at dose level 4.
- Three partial responses in cutaneous T-cell lymphoma patients at dose levels 2, 4, and 5.
- Stable disease observed in four solid tumor patients at dose levels 3-4.
- Dose-dependent increases in KT-333 plasma exposure achieved efficacious levels.
- Favorable immunomodulatory response noted, suggestive of sensitivity to anti-PD1 treatment.
- KT-333 was generally well-tolerated with no dose-limiting toxicities observed in lymphoma or solid tumor patients at the time of cut-off.
- Two dose-limiting toxicities reported at dose level 5, including Grade 3 stomatitis and arthralgia.
- Grade 3 stomatitis was the only serious adverse event related to KT-333.
Insights
The interim clinical data from the Phase 1 trial of KT-333 offers a promising look at the potential of this first-in-class STAT3 degrader in treating hematologic and solid tumor cancers. The reported complete and partial responses in patients with classic Hodgkin’s lymphoma (cHL) and cutaneous T-cell lymphoma (CTCL) are particularly encouraging. The maximum degradation of STAT3 up to 97.5% and the activation of an IFN-γ stimulated gene signature could suggest a favorable immunomodulatory response, potentially enhancing the effectiveness of subsequent anti-PD1 therapies. However, the occurrence of dose-limiting toxicities at higher doses requires careful consideration. Investors should note that while early results are promising, additional data from ongoing studies will be critical to determining the therapy's overall efficacy and safety profile in a larger patient population.
Kymera Therapeutics' presentation of the interim results for KT-333 represents a significant milestone for the company. The positive clinical responses in Phase 1 suggest potential for a strong pipeline asset in the oncology market. Investors should focus on the planned data updates later in 2024, which could act as potential catalysts for the stock. However, considering the early-stage nature of the trials, the results must be viewed with cautious optimism. The adverse events observed, although not uncommon in oncology treatments, highlight the need for ongoing monitoring. The company's ability to navigate these clinical challenges and maintain a favorable safety profile will be important for long-term success and market acceptance.
Abstract released today highlights safety, pharmacodynamic and clinical response data collected through February 6, 2024 cut-off date
Updated data to be presented at the European Hematology Association (EHA) Annual Meeting
KT-333 Phase 1 study ongoing with additional data expected in the second half of 2024
WATERTOWN, Mass., May 14, 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 that new Phase 1 data for KT-333, a first-in-class degrader of STAT3, highlighting safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical responses will be presented at the European Hematology Association (EHA) Annual Meeting, taking place from June 13-16, 2024, in Madrid, Spain. Results released in an EHA abstract today, which include a data cut-off as of February 6, 2024, demonstrate that KT-333 is a potent and selective STAT3 degrader that has demonstrated clinically significant responses in specific patient populations. The poster presentation is expected to include additional data, including PK/PD, safety and results of disease response assessments from additional patients subsequent to the abstract cut-off date.
“We’re encouraged by the Phase 1 data generated to date. We have demonstrated clinically significant responses in specific patient populations, including cHL and CTCL, at tolerated doses. We have also achieved substantial target knockdown and pathway activation,” said Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics. “We look forward to completing the Phase 1 study and sharing additional updates on this first-in-class program across a range of indications later this year.”
Highlights of the KT-333 Clinical Abstract
The abstract reported Phase 1 data from 39 patients enrolled through six dose levels (DL) with a mean of 8.7 doses, including patients with classic Hodgkin’s lymphoma (cHL), B-cell non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), large granular lymphocytic leukemia (LGL-L), T-cell prolymphocytic leukemia (T-PLL) as well as solid tumors. Highlights include:
- Two complete responses in two cHL patients at DL4, three partial responses in CTCL patients at DL2, 4 and 5, and stable disease in four solid tumor patients at DL3-4.
- KT-333 achieved maximum degradation up to
97.5% in peripheral blood mononuclear cells at DL1-5 in Cycle 1 with evidence of STAT3 pathway inhibition and downregulation of inflammatory biomarkers in whole blood. Notably, KT-333 resulted in robust reduction of STAT3, pSTAT3, and SOCS3 expression in a CTCL tumor biopsy in DL4. - Induction of an IFN-γ stimulated gene signature predictive of sensitivity to anti-PD1 was seen in both peripheral blood and tumor, suggestive of favorable immunomodulatory response in the tumor microenvironment following KT-333 treatment.
- Dose dependent increases in KT-333 plasma exposure were observed, achieving levels predicted to be efficacious.
- KT-333 was generally well-tolerated with the most common adverse events being stomatitis, nausea, ALT increase, constipation and fatigue. Two dose-limiting toxicities (DLTs) were observed at DL5 including Grade 3 stomatitis and arthralgia in two separate LGL-L patients. No DLTs were observed in lymphoma or solid tumor patients at the time of the cut-off. Grade 3 stomatitis was also the only KT-333 related serious adverse event.
The Phase 1a trial for KT-333 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.
Poster Presentation at EHA
Title: Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of KT-333, a Targeted Protein Degrader of STAT3, in Patients with Relapsed or Refractory Hematologic and Solid Tumor Cancers
Abstract ID Number: P2040
Presenter: Aditi Shastri, MD, Montefiore Medical Center and Albert Einstein College of Medicine
About KT-333 STAT3 Degrader
KT-333 is a potent, highly selective degrader of STAT3 in development for the treatment of multiple STAT3-dependent pathologies, including hematological malignancies and solid tumors. STAT3 is an undrugged 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. In certain malignant cells, STAT3 activation is set into overdrive, leading to a dampened immune response, tumor progression, and metastasis. STAT3’s role as a cancer driver and tumor microenvironment modulator has been validated in a multitude of studies, making it a strong candidate to target in the treatment of cancer. KT-333 was the first degrader against an undrugged transcription factor to enter the clinic and the Phase 1 clinical trial 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. Clinical data from the KT-333 Phase 1 trial has shown evidence of STAT3 targeted protein degradation in humans with associated STAT3 pathway inhibition, along with early signs of antitumor activity, highlighting the potential of heterobifunctional degraders for targeting this previously undruggable transcription factor. The Phase 1a trial for KT-333 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-333; 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.
Investor and Media Contact: Justine Koenigsberg Vice President, Investor Relations investors@kymeratx.com media@kymeratx.com 857-285-5300 |
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