New MTX-531 Research in Nature Cancer Highlights Promising Dual Inhibitor Strategy for Overcoming
Cancer Resistance
MINNEAPOLIS, July 11, 2024 — 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 preclinically and clinically.
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 that have not yet been observed with 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 and improvement in survival improvement ranged
from 62% to >500% across models.
In addition, when combined with a MEK (trametinib) or a KRAS (sotorasib) inhibitor, 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 shows 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 Institutes
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.
Company Contact:
[email protected]
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.
