Innovative pro-drug delivers superior efficacy with improved drug-like properties and safety profile
CAMBRIDGE, MA / ACCESSWIRE / March 28, 2024 / SynDevRx, Inc., a pioneering clinical-stage biotechnology company based in Cambridge, Massachusetts, has achieved a significant milestone. The company is delighted to announce the publication of a peer-reviewed research paper describing its optimized MetAP2 inhibitor, evexomostat/SDX-7320, targeting tumors sensitive to systemic metabolic dysfunction resulting from obesity, insulin resistance or induced by other cancer treatments. Published in the respected Molecular Cancer Therapeutics (MCT), a journal of the American Association for Cancer Research, the paper details the physicochemical and pharmacological properties of evexomostat and describes how the company's insights into polymer conjugation led to this optimized MetAP2 inhibitor with improved activity, better drug-like properties and enhanced safety profile over prior MetAP2 inhibitors [https://doi.org/10.1158/1535-7163.MCT-23-0574].
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The publication highlights evexomostat's precision in targeting the methionine aminopeptidase 2 (MetAP2) enzyme, a crucial player in angiogenesis, tumor growth and metabolic hormone regulation that cancer cells exploit for proliferation and metastatic spread. Importantly, with respect to the drug class, the Company's polymer conjugation approach minimized CNS exposure while still providing excellent drug-like properties plus potent anti-tumor and anti-metastatic activity in multiple preclinical models of cancer.
Peter Cornelius, Ph.D., the company's Senior Director of Translational Research and lead author of the publication, expressed his enthusiasm: "The first publication of our findings represents an important milestone in the development of evexomostat/SDX-7320. Our novel polymer-drug conjugate addresses critical issues that halted development of prior fumagillin-class MetAP2 inhibitors and demonstrates anti-tumor activity in vivo at low doses of active small molecule, a feature not seen with other polymer-drug conjugates." The SynDevRx team has dedicated years advancing the science of MetAP2 inhibition in cancer, building on the extensive body of MetAP2 research stemming from the discovery by Donald Ingber, MD, Ph.D., in the lab of the esteemed Dr. Judah Folkman, as well as additional subsequent research from Craig Crews, Ph.D., Tyler Jacks, Ph.D., and many others.
Dr. Ingber expressed his hopes for evexomostat's clinical success: "Since my original discovery of this MetAP2 class of cancer therapeutics, I've long wanted to see its potential realized in patients. I'm excited at the progress SynDevRx has made with evexomostat, its advancement into multiple clinical trials and, hopefully, its eventual clinical approval."
SynDevRx's CEO, Bradley Carver, reflected upon the impact of this achievement: "The recognition of our work by the scientific community underscores the game-changing nature of our approach to polymer-drug conjugation. MetAP2 inhibitors have consistently and repeatedly demonstrated clinical activity in studies for both cancer and obesity/diabetes. However, toxicities associated with small molecules from the class have prevented that clinical promise from being fulfilled. Our optimized MetAP2 inhibitor drug conjugate advances the work of other scientists culminating with a greatly improved drug candidate. As we pursue ongoing clinical trials, our focus remains on transforming the lives of patients battling cancer while simultaneously enhancing their quality of life through improvements to their metabolic health."
In addition to the preclinical work described in the current research paper, SynDevRx has completed a Phase I dose-escalation safety trial of evexomostat in late-stage cancer patients, and currently has two open/enrolling clinical trials: the Amelia™-1 trial (www.amelia1.com) in HR+/Her2- metastatic breast cancer in combination with a PI3K/Akt pathway inhibitor plus fulvestrant; and the Aretha trial (www.aretha1.com), a first-of-its-kind Phase 1b/2 study for patients with triple-negative breast cancer (mTNBC) and baseline insulin resistance in combination with standard-of-care therapy eribulin/Halaven®. The Aretha clinical research study is being conducted in collaboration with New York's Memorial Sloan Kettering Cancer Center (MSK) and is being led by Dr. Neil Iyengar.
SynDevRx is committed to leveraging its scientific leadership and expertise in the emerging field of metabo-oncology - the intersection of cancer and metabolic dysfunction. For more details about the paper and its content, please contact Peter Cornelius, Ph.D. For all other questions relating to evexomostat development, please contact:
James Shanahan, Chief Business Officer, SynDevRx, Inc.
Phone: (617) 401-3110
Website: www.syndevrx.com
About SynDevRx
SynDevRx, a clinical-stage company located in the biotech hub of Cambridge, MA, is at the forefront of biotechnological innovation, focusing on developing novel therapies that target the intersection of cancer and metabolic dysfunction - i.e., metabo-oncology. With a commitment to creativity and a passion for life-changing scientific breakthroughs, SynDevRx is dedicated to addressing not just a patient's cancer, but also the pernicious effects of systemic dysregulated metabolic hormones. Our aim is to empower patients and their healthcare providers with new options that allow them not just to survive but to thrive, during and after treatment.
About Evexomostat (SDX-7320)
Evexomostat (SDX-7320) is a polymer drug-conjugate that is among the first drugs being developed specifically for cancer patients with metabolic complications, such as insulin resistance, obesity, diabetes, or pre-diabetes either intrinsic to the cancer patient or resulting from treatment. For patients with certain solid tumors, dysregulated metabolic hormone signaling can promote tumor growth and/or metastasis via known oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by inhibition of its target enzyme MetAP2, simultaneously impacting downstream oncogenic and metabolic pathways. Evexomostat is intended to work with standard-of-care anti-cancer therapies to improve clinical outcomes.
Contact Information
James Shanahan
CBO
jshanahan@syndevrx.com
(617)4013110
SOURCE: SynDevRx, Inc.
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