Pre-clinical data showing effects of the MetAP2 inhibitor evexomostat (SDX-7320) on glycemic control alone and in combination with the Akt inhibitor capivasertib (AZD-5363) will be presented
Results of tumor growth inhibition in a Her2+ xenograft model of breast cancer in response to evexomostat (SDX-7320) and capivasertib/AZD-5363 alone and in combination will be presented
Changes in the expression of key hypoxia, innate immune system, and other genes in tumors following treatment with evexomostat (SDX-7320) will also be presented
SAN ANTIONIO & CAMBRIDGE, Mass., December 08, 2021--(BUSINESS WIRE)--SynDevRx, Inc., a clinical-stage biotechnology company leading the development in treatments for cancers sensitive to dysregulated metabolic hormones, today announced they will be presenting pre-clinical mechanistic/molecular data with evexomostat (SDX-7320) using the Her2+ xenograft model (BT474) in combination with capivasertib/AZD-5363 during the 2021 San Antonio Breast Cancer Symposium.
Akt inhibitors frequently cause severe elevations in blood glucose. Hyperglycemia is a highly problematic, on-target toxicity associated with Akt inhibition that can lead to treatment resistance (which is likely mediated via subsequent hyperinsulinemia) or dose reductions. Furthermore, this on-target effect can require intense medical support, often from outside endocrinologists. Balancing capivasertib-induced hyperglycemia via dose titration while also titrating anti-diabetic medications to remediate the high blood sugar can be challenging and may lead to sub-optimal cancer treatment.
SynDevRx will be presenting data based on a series of experiments that investigated the impact of evexomostat (SDX-732) on Akt treatment-induced hyperglycemia, as well as the anti-tumor effects of evexomostat when combined with capivasertib. Mechanistically, data showing changes in the expression of a number of key hypoxia and innate immune system gene sets will be presented.
The poster, P5-05-04 "Inhibition of HER2+ tumor growth with SDX-7320, a novel MetAP2 inhibitor, alone and in combination with capivasertib/AZD-5363: Reduced expression of hypoxia-inducible genes" is being presented on Friday, December 10 from 7:00-8:30 AM.
SynDevRx believes that evexomostat (SDX-7320) is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or high HbA1c, pre-diabetes or insulin/leptin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, improvements in key lipids, and inhibition of the important angiogenic proteins bFGF and VEGF-C, as was demonstrated in a Phase 1 clinical study in late-stage cancer patients. In preclinical studies using models of breast cancer, evexomostat (in combination with a CDK4/6 inhibitor) decreased levels of multiple cell cycle proteins in ER+ tumors, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed obesity-induced immune suppression within the tumor micro-environment of tumor-bearing obese mice. Evexomostat (SDX-7320) is being developed for use in combination with standard-of-care cancer therapies for breast and prostate cancers.
About SynDevRx, Inc.
SynDevRx is a privately held clinical-stage biopharmaceutical company based in Cambridge, Mass. that is leading the research and development of treatments that address the interactions between cancer and dysregulated metabolic hormones. – i.e., metabo-oncology. Obesity, pre-diabetes and type 2 diabetes are known to worsen certain cancer patients’ prognoses, but oncologists have no specific tools to treat systemic or treatment-induced metabolic complications, except for diet and exercise. SynDevRx is initiating a series of proof-of-concept clinical studies of its drug candidate evexomostat (SDX-7320) to show that improving these hormones together with effects on angiogenesis and the tumor micro-environment will result in better patient outcomes, thereby establishing a new and complementary treatment paradigm for tens of thousands of cancer patients. For more information visit www.syndevrx.com.
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