evexomostat (SDX-7320) / SynDevRx - LARVOL DELTA

Aretha trial: Safety run-in results of eribulin + evexomostat in metastatic triple-negative breast cancer with metabolic dysfunction (SABCS 2025) - P2 | "Evexomostat + eribulin safety was confirmed and the trial advanced to the randomization phase including a placebo-controlled arm with eribulin. Preliminary biomarker results indicate that insulin resistance was unchanged, and favorable changes were seen in other metabolic markers."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LEP • METAP2 • RETN • VEGFC • VEGFD

The methionine aminopeptidase-2 inhibitor, evexomostat, potently suppresses tumour growth in aggressive variant prostate cancer models (ESMO 2025) - "Our findings support the advancement of SDX-7320 into clinical trials for patients with AVPC metastases, where there is a high clinical need for effective novel therapeutics. Legal entity responsible for the study The authors."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • METAP2 • MYC

A phase 1 safety study of evexomostat (SDX-7320) in late-stage cancer patients: an anti-angiogenic, insulin-sensitizing drug conjugate targeting MetAP2. (PubMed, Cancer Res Commun) - "Evexomostat (SDX-7320) was well-tolerated with prolonged stable disease and metastatic control in an open-label, Phase I safety study. Improvements were observed in angiogenic and metabolic biomarkers."

Journal • P1 data • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • FGF2 • LEP • METAP2 • VEGFC

The AmeliaTM-1 study: A phase 1b/2 study assessing the safety and efficacy of evexomostat (SDX-7320) plus a PI3K/Akt inhibitor and fulvestrant in patients with advanced HR+/Her2- breast cancer (SABCS 2024) - P1/2 | "Agents approved or in late-stage development for treating this patient population (alpelisib, capivasertib, inavolisib) can cause on-target hyperglycemia leading to hyperinsulinemia which may limit effectiveness of these drugs by overcoming pathway inhibition and/or secondary to reduced dose-density. QoL will be analyzed according to functional scores and recommendations in the EORTC scoring manual. ECOG performance status and change from baseline will be summarized."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • METAP2 • PIK3CA • PTEN

Evexomostat/SDX-7320 demonstrates potent anti-tumor effects across stages of prostate cancer progression, including treatment refractory and neuroendocrine (AVPC) phenotypes (PCF 2024) - P1/2, P2 | "SDX-7320 treatment was also evaluated in LuCaP35.CR patient-derived xenograft (PDX) in castrate mice as well as in combination with enzalutamide following development of resistance to 10mg/kg daily enzalutamide treatment. These results indicate the importance of MetAP2 regulation throughout multiple stages of prostate cancer development and that its inhibition via evexomostat/SDX-7320 is a novel approach to treat prostate cancer warranting immediate clinical translation."

Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD34 • METAP2 • MYC

Pharmacological Characterization of SDX-7320/Evexomostat: a Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-Tumor and Anti-Metastatic Activity. (PubMed, Mol Cancer Ther) - "Unlike polymer-drug conjugates in general, reductions in small molecule-equivalent efficacious doses following polymer conjugation were observed. SDX-7320 has completed a Phase 1 clinical safety study in late-stage cancer patients and is currently being evaluated in multiple Phase 1b/2 clinical studies in patients with advanced solid tumors."

Journal • Metastases • Oncology • Solid Tumor • METAP2

Amelia-1: Evexomostat Plus Alpelisib and Fulvestrant in Women With the PIK3CA Mutation With HR+/Her2- Breast Cancer (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: SynDevRx, Inc. | Phase classification: P1b/2 ➔ P1/2

Metastases • Phase classification • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

First Patient Treated in Innovative Clinical Study ’Amelia-1’, Testing the Novel Investigational Drug Evexomostat Plus a PI3K Inhibitor in Late-Stage Breast Cancer Patients (Newswire) - "SynDevRx, Inc. today announced the opening of the Amelia-1 study and data from the first patient treated in its Phase 1b/2 clinical study testing the novel MetAP2 inhibitor evexomostat (aka SDX-7320) in combination with the PI3K inhibitor alpelisib (Piqray^®) and the estrogen receptor degrader (SERD) drug fulvestrant (Faslodex^®) in breast cancer patients with metastatic disease and the PIK3CA gene mutation (NCT05455619 - Phase 1b/2 Study of the Safety and Efficacy of Evexomostat Plus Alpelisib and Fulvestrant in Postmenopausal Women at Risk for Hyperglycemia With Advanced Breast Cancer and a PIK3CA Mutation Following Endocrine Therapy and a CDK4/6 Inhibitor)."

Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PIK3CA

The ARETHA study: A phase 2 randomized control trial of eribulin with evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer (TNBC) and metabolic dysfunction. (ASCO 2023) - P2 | "As of Feb 2022, 3 patients are enrolled; total accrual of 61 patients is planned with a goal of 55 evaluable patients. Clinical trial information: NCT05570253."

Clinical • Metastases • P2 data • Breast Cancer • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Solid Tumor • Triple Negative Breast Cancer • Type 2 Diabetes Mellitus

The Amelia-1 study: A phase 1b/2 trial of evexomostat (SDX-7320) plus fulvestrant and alpelisib in patients with advanced breast cancer at risk for alpelisib-induced hyperglycemia. (ASCO 2023) - P1b/2 | "ECOG performance status and change from baseline will be summarized. Clinical trial information: NCT05455619."

Clinical • Metastases • P1/2 data • Breast Cancer • Diabetes • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Evexomostat: A novel therapeutic in development for the treatment of prostate cancer (AACR 2023) - P1b/2, P2 | "Group 3 (n=13/group) and Group 4 (n=14/group) were castrated and randomized to Vehicle or SDX-7320 at recurrence of tumor growth with Group 4 additionally receiving enzalutamide (10 mg/kg, p.o., QD). MetAP2 inhibition has potential as a new approach for the treatment of prostate cancer. The clinical-stage MetAP2 inhibitor evexomostat/SDX-7320 significantly inhibited the growth of LNCaP tumors in intact, castrated and CRPC mice. Clinical evaluation of evexomostat in castration-sensitive as well as castration-resistant prostate cancer patients is warranted."

Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD31 • CD34 • PECAM1

New Experimental Treatment for Prostate Cancer Revealed at AACR (Newswire) - "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."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

The Amelia-1 Study: A phase 1b/2 trial of evexomostat (SDX-7320) plus fulvestrant (Faslodex®) and alpelisib (Piqray®) in patients with advanced breast cancer at risk for alpelisib (Piqray)-induced hyperglycemia (SABCS 2022) - P1b/2 | "QoL will be analyzed according to functional scores and recommendations in the EORTC scoring manual. ECOG performance status and change from baseline will be summarized."

Clinical • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

[VIRTUAL] SDX-7320, a novel inhibitor of methionine aminopeptidase 2 (MetAP2), inhibits MCF-7 tumor growth in combination with palbociclib (Ibrance®) (AACR 2021) - P1 | "In addition SDX-7320 synergized with the PI3Kα inhibitor alpelisib (Piqray®) to block the growth of ER+/Her2- MCF-7 xenografts. Intracellular pathways and proteins linked to emergence of resistance to palbociclib include cell cycle (cyclin E1), growth factor and hormone signaling (Akt, ERα) and autophagy (LC3B). The protein changes observed (representative of these pathways) suggest that combining SDX-7320 with palbociclib (Ibrance®) may extend the period of progression-free survival in patients with ER+/Her2- breast cancer relative to treatment with palbociclib (Ibrance®) alone."

Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCNE1 • CDK2 • ER • HER-2

Synergistic inhibition of MCF-7 mammary gland tumor growth with Piqray® (alpelisib) plus SDX-7320, a novel polymer-conjugated methionine aminopeptidase 2 (MetAP2) inhibitor (SABCS 2019) - P1; "These results show that SDX-7320 (8 mg/kg) is synergistic with Piqray®(alpelisib; 25 mg/kg) in control of orthotopic MCF-7 mammary gland tumors. A clinical trial combining SDX-7320 with Piqray®(alpelisib) plus fulvestrant is planned to start in Q1/2020 and will assess the ability of SDX-7320 to enhance the efficacy of Piqray®(alpelisib) in treating PI3K-mutated, ER+/Her2- breast cancer."

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • EIF4EBP1 • ER • HER-2 • LEP

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 and innate-immune system genes (SABCS 2021) - P1 | "In prior models of breast cancer, SDX-7320 significantly inhibited the growth of syngeneic EO771 triple-negative breast cancers (TNBC) accelerated by obesity/metabolic dysfunction (i.e., “metabo-oncology”) and also synergized with the PI3Kα inhibitor alpelisib/Piqray ® in ER + /Her2- MCF-7 xenografts. In summary SDX-7320 significantly inhibited the growth of BT-474 xenografts, alone and in combination with capivasertib/AZD-5363, which was associated with suppression of hypoxia-induced genes, as well as genes of the innate immune system. In addition, SDX-7320 improved the safety profile of capivasertib/AZD-5363 by attenuating Akt/mTOR inhibitor-induced hyperglycemia, providing further support for the clinical exploration of SDX-7320 in combination with Akt/mTOR inhibitors in Her2 + breast cancer."

Combination therapy • Breast Cancer • HER2 Breast Cancer • Oncology • Triple Negative Breast Cancer • PIK3CA • SESN2

A novel polymer-conjugated methionine aminopeptidase 2 (MetAP2) inhibitor SDX-7320 inhibits the growth of EO771 mammary gland tumors and ameliorates the immunosuppressive tumor immune micro-environment (TIME) (AACR 2019) - P1; "SDX-7320 is being developed to treat cancers whose growth is accelerated by obesity and metabolic dysfunction. Now nearing completion of Phase I (NCT02743637), further clinical trials with SDX-7320 in combination with other therapies are planned for 2019."

The ARETHA Study: A phase 2 randomized control trial of Eribulin with Evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer and metabolic dysfunction (SABCS 2022) - "For any inquiries/questions, please contact Sherry Shen at shens1@mskcc.org. Clinical trial registry number: pending"

Clinical • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Amelia-1: Evexomostat Plus Alpelisib and Fulvestrant in Postmenopausal Women at Risk for Hyperglycemia With Breast Cancer (clinicaltrials.gov) - P1b/2 | N=52 | Recruiting | Sponsor: SynDevRx, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • FGF2 • HER-2 • LEP • PIK3CA • VEGFC

A Study of SDX-7320 in Combination With Eribulin for People With Breast Cancer (clinicaltrials.gov) - P2 | N=55 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Combination therapy • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

New Phase 1b/2 Clinical Research Study with SynDevRx Drug Evexomostat (SDX-7320) Announced for Triple-Negative Breast Cancer Patients with Baseline Insulin Resistance (Businesswire) - "SynDevRx, Inc. today announced the opening of a first-of-its-kind Phase 1b/2 study for patients with triple-negative breast cancer and baseline insulin resistance, testing the novel study drug evexomostat (SDX-7320) in combination with standard-of-care treatment Halaven® (eribulin, Esai)."

New P1/2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

SynDevRx To Present Pre-Clinical Combination Data of Evexomostat (SDX-7320) with Capivasertib (AZD-5363) During The 2021 San Antonio Breast Cancer Symposium (Businesswire) - "Pre-clinical data showing effects of the MetAP2 inhibitor evexomostat (SDX-7320) on glycemic control alone and in combination with the Akt inhibitor capivasertib (AZD-5363) will be presented; Results of tumor growth inhibition in a Her2+ xenograft model of breast cancer in response to evexomostat (SDX-7320) and capivasertib/AZD-5363 alone and in combination will be presented; Changes in the expression of key hypoxia, innate immune system, and other genes in tumors following treatment with evexomostat (SDX-7320) will also be presented."

Preclinical • Breast Cancer • Oncology

SynDevRx Announces Research Collaboration with Queensland University of Technology (QUT) to Study the Effects of SDX-7320 In Advanced Prostate Cancer Models (Businesswire) - "Studies aim to quantify the ability of SynDevRx MetAP2 inhibitor evexomostat (SDX-7320) to control tumor growth of castration resistant prostate cancers...SynDevRx, Inc...announced a research collaboration with Australia’s Queensland University of Technology. The collaboration with Professor Colleen Nelson, PhD, and her team will study the role of methionine aminopeptidase 2 (MetAP2) inhibition in tumor growth in castration resistant and other treatment resistant forms of prostate cancer."

Licensing / partnership • Genito-urinary Cancer • Oncology • Prostate Cancer

[VIRTUAL] SDX-7320 elicits improvements in tumor-related and metabolic biomarkers: Results of a phase 1 dose-escalation study in patients with advanced refractory or late-stage solid tumors (AACR-I 2020) - "32 patients with an average of 5.3 prior treatment regimens were dosed. Sub-cutaneous dosing of SDX-7320 began at 1.7 mg/m2 once per week (Q7D, 28 days/cycle) and was escalated to 49 mg/m2. Repeated Q7D administration at 49 mg/m2 resulted in dose-limiting (G3-G4) thrombocytopenia."

Biomarker • Clinical • P1 data • LEP

SynDevRx Assembles Prostate Cancer Medical Advisory Board to Oversee Drug Candidate That Targets Link Between Obesity and Prostate Cancer (PharmiWeb) - "Joining Dr. Zetter on the PCMAB are:...Dr. David Nanus, MD...where he conducts clinical and basic research focused on molecular abnormalities related to the development and treatment of genitourinary cancers."

Announcement