Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage
biopharmaceutical company advancing targeted protein degradation
(TPD) to deliver novel small molecule protein degrader medicines,
reported preclinical data highlighting the therapeutic potential in
liquid and solid tumors of potent and selective heterobifunctional
degraders of MDM2, including KT-253. The data was presented at the
AACR-NCI-EORTC International Conference on Molecular Targets and
Cancer Therapeutics on October 11-15, 2023, in Boston,
Massachusetts and will also be shared at the 10th International
MDM2 Workshop taking place October 15-18, 2023, in Tokyo, Japan.
MDM2 is a crucial regulator of the most common tumor suppressor,
p53. p53 remains intact (wild type) in approximately 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 cannot
overcome the induced feedback loop that increases MDM2 protein
levels, which can repress p53 and thereby limit their efficacy. In
preclinical studies, MDM2 degraders have demonstrated the ability
to overcome the MDM2 feedback loop observed with MDM2 SMIs and
rapidly induce cell death in sensitive p53 wild-type cancer cell
lines, even with brief compound exposure. This may enable an
improved therapeutic index, which could result in a superior
efficacy and safety profile over MDM2 SMIs.
The Company previously presented data on KT-253, its lead MDM2
degrader, showing greater than 200-fold higher growth inhibition
potency in vitro against p53 wild-type cancer cell lines compared
with MDM2 SMI and a favorable pharmacological profile. Results
shared at the 10th International MDM2 workshop show potent in vivo
activity of a single dose of KT-253 in models of AML and ALL as
well as activity in combination with clinical and sub-clinical
doses of venetoclax in a venetoclax-resistant AML model. KT-253 is
currently being evaluated in a Phase 1 trial in liquid and solid
tumors and the Company plans to share data regarding
proof-of-mechanism from its Phase 1 trial later this year.
Work completed in collaboration with the Dana-Farber Cancer
Institute and presented at both congresses support MDM2 degradation
as a promising therapeutic approach in Merkel cell carcinoma (MCC),
a high-grade neuroendocrine carcinoma of the skin. These data
demonstrate in vitro efficacy of an MDM2 degrader, KTX-049, against
p53 wild-type MCC cell lines that was achieved with brief compound
exposure. In two MCC PDX models, KT-253 (referred to as KTX-169 in
the presentation) demonstrated tumor regressions with weekly as
well as every three-week dosing whereas an MDM2 SMI only showed
modest tumor growth inhibition.
“These compelling results with MDM2 degraders exemplify our
approach of selecting targets with strong genetic validation where
we believe that targeted protein degradation provides the best
chance for an effective treatment. They also support the potential
of MDM2 degradation to overcome the inherent limitations of MDM2
SMIs to more effectively stabilize p53 and thereby induce cancer
cell death in sensitive p53 wild type liquid and solid tumors, both
alone and in combination with widely used treatments,” said Jared
Gollob, M.D., Chief Medical Officer, Kymera Therapeutics. “We aim
to drive meaningful improvements in efficacy as well as safety and
tolerability over MDM2 small molecule inhibitors through
intermittent dosing of our MDM2 degrader, and are currently
evaluating KT-253 dosed every three weeks in a variety of liquid
and solid tumors in our ongoing Phase 1 trial.”
Presentation at the AACR-NCI-EORTC International
Conference on Molecular Targets and Cancer
Therapeutics:
- Title: The MDM2 degrader KTX-049 is highly potent in TP53
wild-type (p53 WT) Merkel cell carcinoma (MCC).
- Abstract Number: C134
- Session Time: Poster Session C, 12:30 PM – 4:00 PM ET, October
14, 2023
- Presenter: Varsha Ananthapadmanabhan, Ph.D., Department of
Medical Oncology, Dana-Farber Cancer Institute, Department of
Medicine, Brigham and Women’s Hospital and Harvard Medical School
Presentations at the 10th
International MDM2 Workshop:
- Title: Development of KT-253, a highly potent and selective
heterobifunctional MDM2 degrader, for the treatment of Acute
Myeloid Leukemia
- Abstract Number: 5
- Session Time: 1:00 PM – 2:00 PM JST, October 16, 2023
- Presenter: Yogesh Chutake, Ph.D., Principal Scientist,
Translational Medicine, Kymera Therapeutics
- Title: Activity of MDM2 degrader KTX-049 in Merkel cell
carcinoma
- Abstract Number: ST19
- Session Time: 10:35 AM – 10:50 AM JST, October 18,
2023
- Presenter: James A. DeCaprio, M.D., Department of Medical
Oncology, Dana-Farber Cancer Institute, Department of Medicine,
Brigham and Women’s Hospital and Harvard Medical School
Copies of the presentations are available online in the
Scientific Resources section of Kymera’s website.
About MDM2 Degrader Program (KT-253)
The KT-253 Phase 1 trial initiated in March 2023 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), lymphoma and solid tumors.
Patients in the KT-253 Phase 1 dose escalation study will receive
IV doses of KT-253 administered once every 3 weeks. The open-label
study is intended to identify the recommended Phase 2 dose for
KT-253, and is comprised of two arms, with ascending doses of
KT-253 in each arm. The first arm will consist of patients with
lymphomas and advanced solid tumors and the second arm will consist
of patients with high grade myeloid malignancies and ALL.
More information on the Phase 1 study can be found at
www.clinicaltrials.gov, identifier NCT05775406.
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 IRAK4, IRAKIMiD, STAT3, and MDM2 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 ability to initiate new clinical programs; and Kymera’s
financial condition and expected cash runway into the second half
of 2025. The words “aim”, "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 those for KT-474 (SAR444656), 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; 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, 2022 and most recent Quarterly Report on
Form 10-Q, 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
Contact: Justine Koenigsberg Vice
President, Investor
Relations investors@kymeratx.com 857-285-5300 |
Media
Contact: Todd Cooper Senior Vice
President, Corporate
Affairs media@kymeratx.com 857-285-5300 |
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