New MTX-531 Research in Nature Cancer Highlights Promising
Dual Inhibitor Strategy for Overcoming Cancer
Resistance
MINNEAPOLIS, July 11,
2024 /PRNewswire/ -- MEKanistic Therapeutics Inc., a
biotechnology company pioneering the development of next-generation
kinase inhibitors for cancer treatment, today announced the
peer-reviewed publication of new preclinical research on its lead
candidate, MTX-531, an investigational dual-targeting therapy, in
Nature Cancer. MTX-531 is a potential first-in-class therapy
uniquely designed to inhibit both EGFR (Epidermal Growth Factor
Receptor) and PI3K (Phosphoinositide 3-kinase), two critical
proteins involved in cancer cell survival and proliferation.
"We are excited to share the positive MTX-531 preclinical
research published in Nature Cancer, which we believe show
promising signals toward a novel solution to addressing the root
cause of resistance to current cancer treatments," said
Danny Cunagin, chief executive
officer, MEKanistic Therapeutics. "By targeting critical adaptive
resistance mechanisms with a dual inhibition strategy, we aim to
significantly halt cancer progression compared to single-target
treatments, and look forward to advancing this innovative
therapy to patients in clinical trials."
Key Findings of MTX-531 Study
High Potency, Selectivity Leading to First of Its Kind
Tolerability
Preclinical studies demonstrated that MTX-531 exhibits nanomolar
potency against both EGFR and PI3K (14.7 nM for EGFR, 6.44 nM for
PI3K), with a high degree of selectivity as determined by broad
kinome testing. In addition, MTX-531 did not cause hyperglycemia in
mice at therapeutic doses, unlike other known pan-PI3K inhibitors,
which have been reported to significantly increase blood glucose
and insulin levels both in preclinical and clinical
settings.
Judith Sebolt-Leopold, PhD, chief
scientific officer, MEKanistic Therapeutics, commented, "MTX-531 is
the first PI3K inhibitor capable of selectively co-targeting EGFR
and the first known pan-PI3K inhibitor that does not induce
hyperglycemia, a known challenge with PI3K inhibitors that often
leads to treatment discontinuation. This unique feature, achieved
through precise targeting enabled by MTX-531's computational
design, confers a favorable therapeutic index and resilience to
adaptive resistance mechanisms not observed in prior PI3K inhibitor
clinical programs."
Robust Tumor Suppression as Monotherapy and in Combination
Therapy
MTX-531 monotherapy led to significant tumor regression in
preclinical models of head and neck squamous cell carcinoma
(HNSCC). Oral therapy effectively inhibited PI3K and EGFR signaling
in a balanced fashion, achieving objective responses in every HNSCC
model evaluated. Complete tumor regressions were observed across a
broad dose range, with survival improvement ranging from 62% to
>500% across models.
In addition, when combined with a MEK inhibitor (trametinib) or
a KRAS inhibitor (sotorasib), treatment with MTX-531 more than
doubled the incidence of tumor regressions achieving a 100%
objective response rate in multiple KRAS mutant colorectal (CRC)
and pancreatic tumor models.
Dr. Sebolt-Leopold added, "Our collective preclinical data
show that MTX-531 effectively inhibits tumor growth in cancers
with PIK3CA and KRAS mutations, which often lead to aggressive
behavior and resistance to standard therapies. MTX-531 was well
tolerated and outperformed the combination of drugs that
individually target EGFR and PI3K. These findings highlight the
versatility and broader potential of MTX-531 in treating
hard-to-treat cancers."
The scientific paper can be accessed at the following link:
https://www.nature.com/articles/s43018-024-00781-6
About MTX-531 Development
Investigational new drug-enabling toxicology studies sponsored
by the National Cancer Institute's Experimental Therapeutics (NExT)
Program are currently underway. The NExT Program aims to advance
clinical practice by supporting promising new drug discovery and
development projects. Through this program, MEKanistic Therapeutics
collaborates with NCI staff and contractors on a milestone-driven
project team to conduct these studies and assess MTX-531's safety
and efficacy in patients with cancer.
"Our partnership with the NCI is a testament to the promising
potential of MTX-531," said Christopher
Whitehead, PhD, co-founder and chief operating officer,
MEKanistic Therapeutics. "With their support and our focused
efforts on GMP manufacturing and drug product development, we are
poised to make significant strides in bringing this innovative
therapy closer to clinical trials and ultimately to patients in
need."
About MEKanistic Therapeutics, Inc.
MEKanistic Therapeutics Inc. is a privately held, Minneapolis, MN based biotechnology company
focused on developing innovative kinase inhibitors for the
treatment of cancer. The company studies the landscape of signal
transduction pathways to create more effective cancer treatments.
By targeting compensatory signaling in response to pathway
intervention, MEKanistic designs drugs that prevent tumors from
developing resistance to targeted therapies. The company's lead
candidate is MTX-531, a single molecule that was rationally
designed to selectively block two key pathways (EGFR and PI3K) that
promote tumor progression. For more information, visit
mekanistic.com and engage with MEKanistic on LinkedIn.
Media Contact:
Priyanka
Shah
priyanka@bioscribe.com
Forward-Looking Statements
This press release may contain "forward-looking statements"
within the meaning of the federal securities laws, which involve
risks and uncertainties including statements regarding the
potential benefits, safety, and efficacy of MTX-531, and which can
be identified by the use of forward-looking terminology such as
"may," "will," "expect," "plan," "anticipate," "believe,"
"estimate," or "continue" or the negative thereof or other
variations thereon or comparable terminology. MEKanistic
Therapeutics Inc. has based these forward-looking statements on its
current expectations and forecasts about future events. Actual
results could differ materially from those projected in such
forward-looking statements due to a number of factors.
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SOURCE MEKanistic Therapeutics, Inc.