Announcement of a new Phase 1b/2 clinical research study with SynDevRx drug Evexomostat (SDX-7320) for patients with triple-negative breast cancer with baseline insulin resistance

CAMBRIDGE, Mass.–(BUSINESS WIRE)–SynDevRx, Inc. today announced the initiation of a first-of-its-kind Phase 1b/2 study for patients with triple-negative breast cancer and drug resistance. basal insulin, testing the new study drug evexomostat (SDX-7320) in combination with the reference treatment Halaven® (eribulin, Esai). Evexomostat is one of the first cancer treatments developed specifically for cancer patients with initial metabolic dysfunction (obesity, type 2 diabetes and prediabetes). The clinical research study is being conducted in collaboration with Memorial Sloan Kettering Cancer Center (MSK) in New York.

Insulin resistance, also known as hyperinsulinemia, is a condition that may go undetected until a patient develops type 2 diabetes mellitus (T2D) or elevated HbA1c. Insulin controls blood sugar, but is also a powerful growth hormone. It has been widely reported that elevated insulin levels in the presence of certain cancers, such as breast cancer1may accelerate tumor growth, make them harder to treat, and lead to premature cancer progression with poorer patient outcomes2. The purpose of this research study is to explore the impact of insulin targeting and improving insulin resistance in combination with standard therapy on treatment response and patient outcomes. This is the first prospective study using a clinical treatment designed specifically to address this critical, but largely understudied, aspect of cancer progression.

Dr. Neil Iyengar, MD, MSK medical breast oncologist and principal investigator of this study, has been at the forefront of research into the negative influences that dysregulated metabolic hormones, such as insulin, play on breast cancer outcomes. treatment of cancer patients.

“Metabolic hormones play an important role in the establishment and progression of cancer, and are likely critical to patient clinical outcomes,” Dr. Iyengar said. “The historically neglected field of metabo-oncology research has gained momentum in recent years and may soon become a critical aspect of cancer treatment. A patient’s metabolic health status is known to impact survival after a cancer diagnosis and, in some cases, the effectiveness and duration of cancer treatment.

“In a previous study, evexomostat (SDX-7320) demonstrated potent effects on elevated insulin levels in patients with advanced cancer, while preventing new metastases in multiple patients and with a profile of acceptable security,” said Bradley Carver, co-founder and CEO of SynDevRx. “Although this clinical study focuses on insulin levels and impacts on TNBC progression, the additional anti-angiogenic effects of evexomostat (SDX-7320) also seen in a Phase 1 study may independently improve clinical benefits for patients. Additionally, oncologists generally do not consider the metabolic health of their patients when designing treatment regimens. This study may change that. Dr. Iyengar’s pioneering research and deep understanding of the population of metabo-oncology patients, along with MSK’s outstanding reputation for outstanding and innovative research, provide the perfect opportunity to showcase the multi-faceted effects of evexomostat (SDX-7320) for cancer patients breast,” says Bradley Carver.

“SynDevRx is at the forefront of metabo-oncology research and drug development, and we appreciate all of the efforts of the MSK team in bringing this new experimental treatment paradigm to patients,” continued Carver. “Dr. Iyengar’s unique experience integrating patients’ metabolic health into their cancer treatment resulted in a study design that we believe could lead to future clinical practices that integrate insulin levels and patients’ overall metabolic health in their cancer treatment regimens.

“SynDevRx establishes global collaborations with leading research institutions focused on the downstream effects that obesity and dysregulated metabolic hormones have on cancer progression and metastasis. We invite other researchers to work with us to unravel these complex and critical interactions between cancer and dysregulated metabolic hormones,” said James Shanahan, co-founder and chief commercial officer of SynDevRx.

  1. Gallagher, EJ, et al., Hyperinsulinemia in cancer. Nat Rev Cancer 20, 629–644 (2020)

  2. Yee LD, et al., Metabolic health, insulin and breast cancer: why oncologists should care about insulin. Front. Endocrinol. 11:58 (2020).

About Evexomostat (SDX-7320)

Evexomostat (SDX-7320) is one of the first drugs developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, hyperglycemia or HbA1c, pre-diabetes or drug resistance. insulin/leptin. For some tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadly. Evexomostat works by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in metabolic hormones insulin, leptin and adiponectin, regulation of key lipids and inhibition of important angiogenic proteins bFGF and VEGF-C, as has been demonstrated in a clinical phase 1 study in patients with terminal cancer. In preclinical studies, evexomostat also directly inhibited several cell cycle signaling pathways, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed immune-induced suppression. by obesity in the tumor microenvironment of obese tumor-bearing mice. Evexomostat is being developed for use in combination with standard clinically indicated cancer treatments for breast and other tumor types.

About SynDevRx, Inc.

SynDevRx is a privately held, clinical-stage biopharmaceutical company based in Cambridge, Massachusetts. which leads the research and development of treatments that address the interactions between cancer and dysregulated metabolic hormones. – that is, metabo-oncology. Obesity, prediabetes and type 2 diabetes are known to worsen the prognosis of some cancer patients, but oncologists have no specific tools to treat systemic or treatment-induced metabolic complications, except exception of diet and exercise. SynDevRx is launching a series of proof-of-concept clinical studies of its drug candidate evexomostat (SDX-7320) to show that enhancement of these hormones along with effects on angiogenesis and tumor microenvironment will lead to better outcomes for patients, establishing a new complementary treatment paradigm for tens of thousands of cancer patients. For more information, visit www.syndevrx.com.

Paul N. Strickland