SynDevRx Announces Positive Data from Phase 1 Safety Trial of SDX-7320 in Late Stage Cancer Patients

SynDevRx has submitted to the FDA results from a Phase 1 dose escalation study in patients with metastatic and progressing solid tumors to assess the safety and tolerability of SDX-7320. Additional outcome measures suggest that SDX-7320 may slow the rate of disease progression and formation of new metastases. Exploratory endpoints suggest that SDX-7320 may induce favorable changes to insulin and insulin resistance and other key metabolic hormones (leptin, adiponectin) as well as to multiple angiogenic biomarkers.

SynDevRx, Inc., a clinical-stage oncology company, has submitted results of its Phase 1 dose escalation safety study in late-stage cancer patients with progressive, metastatic solid tumors to the United States Food and Drug Administration (FDA) [1]. The study’s primary endpoint was to establish the maximum tolerated dose and dosing schedule and the recommended Phase 2 dose for SDX-7320, the company’s lead drug candidate for the treatment of metabolically sensitive cancers [2]. Secondary and exploratory endpoints included analysis of anti-tumor efficacy and changes in key angiogenic and metabolic biomarkers.

The study evaluated data from 32 patients, whose disease progression and new lesion formation were measured at intervals of every 2 months from the initiation of treatment. Exploratory changes from baseline to metabolic hormones were measured, including leptin and adiponectin, as well as changes to insulin levels and insulin sensitivity (HOMA-IR). Exploratory changes from baseline to angiogenesis biomarkers bFGF, VEGF, and IGF-1 were also evaluated. A total of 28 patients had at least one tumor burden assessment performed, of whom 21 (75%) had at least one stable disease determination before leaving the study or experiencing progressive disease. Of these 21 patients, the period of measurable stable disease averaged 85 days. There were no objective partial or complete responses.

“The results of our Phase 1 trial suggest that SDX-7320 may have potent anti-angiogenic activity, appears to induce favorable changes to insulin, leptin and adiponectin, and has a safety profile that supports future combination studies. These data provide us with the scientific rationale for future clinical studies in tumors that are sensitive to metabolic hormones, i.e., metabo-oncology,” said Brad Carver, President and CEO of SynDevRx. “Animal data we previously presented at the San Antonio Breast Cancer Symposium in 2019 showed that SDX-7320 attenuated the hyperglycemia and hyperinsulinemia caused by the PI3K inhibitor alpelisib, and showed synergistic tumor growth inhibition in mice. Considering the aforementioned data together with this clinical data, we believe SDX-7320 could provide real benefit to breast cancer patients taking a PI3K inhibitor. We expect to open enrollment for our upcoming clinical trial in metastatic ER+/Her2- breast cancer patients with a mutation in the PIK3CA gene early next year, followed by additional trials focused on triple-negative breast cancer and prostate cancer, tumor types that are highly sensitive to systemic metabolic dysfunction.”

About the Study:

SynDevRx’s Phase 1 dose escalation study was designed to assess the safety and tolerability of SDX-7320 in patients with advanced refractory or late-stage solid tumors (lung, colon, breast, rectal, pancreatic, appendiceal, carcinoid, cholangiocarcinoma, cervical, endometrial, hepatocellular, and urothelial cancers). [3] Patients were a mean age of 66 years old and had progressed following five prior lines of treatment for their metastatic disease, on average.

SDX-7320 was administered subcutaneously at doses ranging from 1.7–65 mg/m2 and induced primarily mild side effects including fatigue, GI symptoms (nausea, abdominal pain, diarrhea), and anemia. The dose-limiting toxicity event, thrombocytopenia, was generally reversible without intervention and was observed only at the highest doses tested. Results of the study suggest that the dose of SDX-7320 at 49 mg/m2 on a once every two weeks (i.e., Q14D) schedule may be appropriate for future studies. [3]

SDX-7320 acts by inhibiting MetAP2, a clinically validated target that appears to play a key role in tumor growth, metastasis, angiogenesis, and metabolic dysfunction. “Many solid tumor types are highly sensitive to dysregulated metabolic hormones, such as insulin, leptin, or adiponectin. These hormones signal through known oncogenic pathways, like PI3K/Akt/mTOR or STAT3. Given the epidemic of metabolic syndrome in the world plus the frequency of tumors that are sensitive to metabolic hormones (e.g., breast and prostate cancers), we believe that SDX-7320 could help clinical oncologists treat their cancer patients with concomitant, systemic metabolic dysfunction in combination with standard-of-care therapies,” said James Shanahan, Co-Founder and Chief Business Officer of SynDevRx.

About SDX-7320:

SynDevRx believes that SDX-7320 is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. SDX-7320 acts by binding irreversibly to the target enzyme MetAP2, triggering improvements in the metabolic hormones, insulin, leptin and adiponectin. Additionally, SDX-7320 inhibits the important angiogenic proteins bFGF and VEGF, and in preclinical studies, inhibited multiple cell cycle signaling pathways and reversed immune suppression within the tumor micro-environment. SDX-7320 is being developed for use in combination with clinically indicated standard-of-care cancer therapies.

SynDevRx and Metabo-oncology:

SynDevRx is pursuing the research and development of therapeutic interventions for cancer patients that also have background metabolic dysfunction. Metabo-oncology is the emerging field of research into, and treatments for cancer patients with tumors that are sensitive to metabolic hormones. Many common cancers are highly sensitive to dysregulated metabolic hormones stemming from overweight/obesity, pre-diabetes (hyperinsulinemia), type 2 diabetes and metabolic syndrome. An estimated 600,000+ patients in the United States alone are diagnosed each year with tumors that fit this category, yet little attention is given to the influence of systemic metabolic dysfunction on cancer progression. While diet and exercise can be effective at mitigating these effects, patients undergoing cancer treatment often find it difficult to adhere to these regimens. Therapeutic interventions are needed.

SynDevRx expects to commence enrollment for clinical studies in breast and prostate cancers that will test whether SDX-7320, when added to standard-of-care treatment, will help these patients more than standard-of-care treatments alone. The first study is in 2nd line metastatic ER+/Her2- breast cancer patients with a PIK3CA mutation, in combination with the PI3Kα inhibitor Piqray® (Novartis). To learn more about SynDevRx upcoming clinical trials, visit: http://www.syndevrx.com/

References:

1. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Apr 19 - . Identifier NCT02743637, A Dose Escalation Study of SDX-7320 in Patients with Advanced Refractory or Late-Stage Solid Tumors (SDX-0101); 2020 Jan 27 [cited 2020 Oct 21]; Available from: https://clinicaltrials.gov/ct2/show/study/NCT02743637?term=syndevrx&draw=2&rank=1
2. Uzunlulu M, Telci Caklili O, Oguz A. Association between Metabolic Syndrome and Cancer. Ann Nutr Metab. 2016;68(3):173-9. doi: 10.1159/000443743. Epub 2016 Feb 20. PMID: 26895247.
3. Abstract CT153: 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. Mita M, Bendell J, Mita AC, Gordon M, Sachdev J, Carver BJ, Shanahan J, Mayes B, Awerkamp K, Browning D, Salomon N, Sullivan K, Anderson-Villaluz A, Johnson J, Petersen JS, Turnquist DJ, Cornelius P. J Cancer Res 2020 (80) (16 Supplement). DOI: 10.1158/1538-7445.AM2020-CT153

About SynDevRx:

SynDevRx is a privately held clinical-stage biopharmaceutical company based in Cambridge, Massachusetts focused on the research and development of treatments that address the underserved needs of cancer patients with systemic metabolic dysfunction – i.e., metabo-oncology. Obesity, pre-diabetes and type 2 diabetes are known to worsen certain cancer patients’ prognosis, but oncologists have no specific tools to treat systemic metabolic complications, except for diet and exercise. SynDevRx intends to initiate a series of clinical studies of its drug candidate SDX-7320 to address this major, unmet medical need. Preclinical studies have shown that SDX-7320 reduces tumor growth and angiogenesis, helps to control aberrant metabolic hormone signaling, and reduces treatment resistance to certain standard cancer therapies in metabolically sensitive cancers. SDX-7320 is being developed for use in combination with standard of care therapies for a variety of solid tumors.