On December 8, 2021 SynDevRx, Inc., a clinical-stage biotechnology company leading the development in treatments for cancers sensitive to dysregulated metabolic hormones, reported 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 (Press release, SynDevRx, DEC 8, 2021, View Source [SID1234596613]).
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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.
About SDX-7320
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.