Safety Run-in Cohort Results Show Anti-tumor Activity Plus Systemic Metabolic Improvements with Evexomostat Plus Eribulin in Late-line Metastatic TNBC Patients

We are tremendously excited by both the unexpected responses we've seen in this challenging patient population and the solid improvements in patients' metabolic health.”
— Dr. Neil M. Iyengar

NEW YORK, NY, UNITED STATES, December 2, 2025 /EINPresswire.com/ -- Memorial Sloan Kettering Cancer Center (MSK), and SynDevRx, the pioneering metabo-oncology company, today announced that safety data from the ARETHA-1 Study will be presented at the San Antonio Breast Cancer Symposium (SABCS). The ARETHA-1 Trial safety run-in results demonstrate the combination of evexomostat, SynDevRx's novel MetAP2 drug conjugate, plus eribulin (Halaven®) in patients with advanced metastatic triple-negative breast cancer (mTNBC) and metabolic dysfunction.

Key Findings from the Safety Cohort:
- Favorable safety profile for the evexomostat plus eribulin combination
- Encouraging clinical response rates in this difficult-to-treat patient population
- Significant improvements in metabolic parameters including body weight, LDL cholesterol, insulin, leptin, and adiponectin levels
- Notable improvements in key angiogenic proteins

The safety cohort enrolled patients with obesity and/or insulin resistance in primarily second or third-line treatment for metastatic triple-negative breast cancer following immune-oncology or ADC or chemotherapy treatments. The clinical hypothesis being tested stems from research suggesting obesity and/or insulin resistance contributes to TNBC aggressiveness through activation of the PI3K pathway, which is up-regulated in obesity and insulin resistance (Salemi 2025, Prvanovic 2021, Qiu 2024). Results include safety data for the combination therapy, response rates, and quite notably, changes in metabolic parameters including body weight and certain adipokines associated with cancer progression.

"We are tremendously excited by both the unexpected responses we've seen in this challenging patient population and the solid improvements in patients' metabolic health," said Dr. Neil Iyengar, Principal Investigator at Emory University (formerly of Memorial Sloan Kettering Cancer Center). "The combination of evexomostat with eribulin has demonstrated not only encouraging anti-tumor activity but also meaningful improvements in patients' weight, insulin sensitivity, and key metabolic hormones like leptin and adiponectin. Perhaps most importantly, we've observed significant improvements in angiogenic proteins, which suggests we're addressing the fundamental metabolic-oncologic connection that drives disease progression in these patients."

Of particular note was the depth and duration of responses in patients with androgen receptor (AR)-positive TNBC – a phenotype that is gaining attention as a potential biomarker for patient stratification (Ma 2025, Walsh 2022, Traina 2018, Medic-Milijic 2024). As obesity is frequently accompanied by insulin resistance, Aretha-1 is testing the clinical hypothesis that evexomostat, with its insulin sensitizing properties (Mita 2025) would potentiate the activity of chemotherapy in TNBC patients with obesity and/or insulin resistance.

“Androgen receptor positivity in TNBC has been controversial in this setting. Now, emerging clinical data suggests that AR+ alone is insufficient as a prognostic tool in TNBC outcomes, and that other, co-activated pathways (such as PI3KAKT which overlap insulin signaling pathways), together confer an aggressive phenotype in TNBC patients.” stated Peter Cornelius, PhD, Sr. Director Translational Research at SynDevRx. “We know that MetAP2 inhibition helps restore insulin sensitivity in late-stage cancer patients and we hypothesize that doing so in metastatic TNBC patients will help improve the effectiveness of concomitant therapies.”

About the ARETHA-1 Study
The ARETHA-1 Trial NCT05570253 is investigating the safety and efficacy of combining evexomostat with chemotherapy (e.g., eribulin) in patients with metastatic triple-negative breast cancer who have metabolic dysfunction, including obesity and/or insulin resistance. This represents the first clinical evaluation of a metabo-oncology agent in breast cancer, targeting both tumor growth and underlying metabolic dysfunction simultaneously.

About Evexomostat (SDX-7320)
Evexomostat is SynDevRx's lead compound, a first-in-class methionine aminopeptidase type II (MetAP2) inhibitor specifically designed for cancer patients with obesity or metabolic dysfunction. Evexomostat features a unique multi-modal mechanism of action that includes positive weight response, anti-angiogenesis, global metabolic dysfunction improvement, cell cycle arrest, and activation of the tumor immune microenvironment. Evexomostat is being tested in combination with PI3K/AKT inhibitors in metastatic HR+/Her2- breast cancer (the Amelia™-1 Study), and in a pilot clinical study in late-stage metastatic ARPI- and castration-resistant prostate cancer patients with the ‘aggressive variant’ form of the disease (EVADE-1).

About Memorial Sloan Kettering
Memorial Sloan Kettering (MSK) is a world-renowned cancer treatment and research institution in New York City, established in 1884. As the world's oldest and largest private cancer center, MSK is dedicated to three main areas: patient care, research, and education.

About SynDevRx
SynDevRx is the pioneering metabo-oncology company based in Cambridge, Massachusetts, dedicated to developing innovative treatments that address both cancer progression and systemic metabolic dysfunction.

James Shanahan
SynDevRx, Inc.
+1 617-401-3110
[email protected]
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