New Experimental Treatment for Prostate Cancer Revealed at AACR
Evexomostat (SDX-7320) shows potent anti-tumor effects in pre-clinical models of prostate cancer, including castration-resistant. New research data to be presented at AACR 2023 in Orlando, FL
ORLANDO, Fla., April 14, 2023 (Newswire.com) - SynDevRx, Inc. today announced it will be presenting new anti-tumor data for its lead drug candidate evexomostat (SDX-7320) at the American Association for Cancer Research in Orlando, Florida on Monday, April 17 starting at 9:00 a.m. local time. The poster will highlight anti-tumor activity in animals with androgen receptor positive (AR+) and in castration-resistant prostate cancer (CRPC). In addition to tumor control, evexomostat demonstrated potent anti-angiogenic activity as well as profound and diverse effects on a broad array of important tumor-promoting genes.
The data was generated in collaboration with Prof. Colleen Nelson, PhD, Founder and Executive Director of the Australian Prostate Cancer Research Centre - Queensland (APCRC-Q) and Chair of Prostate Cancer Research at Queensland University of Technology (QUT). The Centre focuses on discovery of new therapeutic targets and their preclinical and clinical development.
Interestingly, while evexomostat had strong anti-tumor activity, it appeared to have a discordant effect on PSA levels - a usual marker of prostate cancer tumor growth and castrate resistant progression. However, as Professor Nelson observed, evexomostat's "effect on PSA seems to be to upregulate it, and we see that as a signal of differentiation back to a more adeno-phenotype." The implications of this pro-differentiation are profound, as it suggests once difficult-to-treat (i.e., more de-differentiated) prostate cancers may become more sensitive to standard androgen-targeted treatments.
SynDevRx has always considered prostate cancer to be among the most important targets for its MetAP2 inhibitor evexomostat. Over half of low-grade and nearly 60% of high-grade prostate tumors have high expression levels of MetAP2, and elevated levels of MetAP2 at diagnosis are associated with shorter time to recurrence1. "This data strongly supports clinical exploration in advanced prostate cancer," noted Peter Cornelius, PhD, Senior Director of Translational Research. "Beyond anti-tumor effects, evexomostat is well positioned to bring multiple clinical benefits to men undergoing treatment for prostate cancer, as current treatments also induce systemic metabolic dysfunction, including insulin resistance and type 2 diabetes. These metabolic disturbances are known to increase risk for disease progression2," he added.
Evexomostat is currently being evaluated in two Phase 1b/2 clinical trials in breast cancer patients with baseline metabolic dysfunction - the Amelia™ 1 Study for HR+/Her2- metastatic breast cancer in combination with Piqray® (Novartis) plus Falsodex® (AstraZeneca) (www.amelia1.com) and in the Aretha-1 Study for women with metastatic triple-negative breast cancer in combination with Halaven® (Eisai) (www.aretha1.com).
"SynDevRx is establishing global collaborations with leading research institutions focused on the effects that dysregulated metabolic hormones have on cancer progression, metastasis and patient outcomes. We invite other researchers to work with us as we untangle these complex and critical interactions between cancer and systemic, dysregulated metabolic hormones," said SynDevRx's co-founder and Chief Business Officer James Shanahan.
- Xie et al., In vivo imaging of methionine aminopeptidase II for prostate cancer risk stratification Cancer Res. 2021 May 01; 81(9)
- Di Sebastiano, et al., (2018) Glucose impairments and insulin resistance in prostate cancer: the role of obesity, nutrition and exercise. Obesity Reviews, 19(7), 1008-1016
About Evexomostat (SDX-7320)
Evexomostat (SDX-7320) is among the first experimental drugs being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or 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 inhibition of the important angiogenic proteins bFGF and VEGF-C plus downstream improvements in the metabolic hormones insulin, leptin and adiponectin, and regulation of key lipids (HDL, LDL), as was demonstrated in a Phase 1 clinical safety study in late-stage cancer patients. In preclinical studies, evexomostat also directly inhibited multiple cell cycle signaling pathways, 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 is being developed for use in combination with clinically indicated standard-of-care cancer therapies for breast and other tumor types.
About SynDevRx, Inc.
SynDevRx is a privately held clinical-stage biopharmaceutical company based in Cambridge, Massachusetts. 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.
Source: SynDevRx, Inc.