BPM 31510 targets the metabolic machinery of the cancer microenvironment to reverse the aerobic glycolytic phenotype of cancer cells also called the Warburg phenotype. The Warburg phenotype has been related to the pathogenesis of schizophrenia, malignancy, metabolic syndrome x, autoimmune disease and neuronal degeneration.
The endogenous small molecule resident in mitochondria restores oxidative phosphorylation and confers re-capitulation of the BCL-2 protein family potential to induce cell death (apoptosis) and disruption in tumor vasculature by modulation of VEGF [1] a process that cancer evades. Mechanistic studies show that BPM 31510 does not adversely affect normal tissue but rather optimizes the bioenergetic balance in the tumor microenvironment to “normalize” a cancer cell into behaving much like a healthy cell.
Interim date presented at ASCO 2012
“Targeting metabolic pathways that differ between cancer cells and normal cells holds considerable promise for cancer therapy. It will be instructive to see if the degree of reversal of the Warburg effect by BPM 31510 correlates with clinical outcomes,” said Vikas P. Sukhatme, MD PhD, Victor J. Aresty Professor of Medicine at Harvard Medical School and Chief Academic Officer at Beth Israel Deaconess Medical Center.
Interim data from a phase I clinical trial on advanced, refractory, solid tumors, presented by Berg Pharma, a Boston-based pharmaceutical company, at the 2012 American Society of Clinical Oncology meeting in Chicago held from June 1 – 5, 2012 showed that BPM 31510 is generally well-tolerated with no serious, dose limiting, toxicities to date. A partial response and minor response were observed and correlates with dose escalation.
Ongoing Study
The Phase I is on-going as the MTD has not been reached to date however, there has already been very encouraging signs of efficacy with 1 patient showing a near complete response in addition to a few significant partial responses and stable disease profile in various patient cohorts. Linda Vahdat, MD, Professor of Medicine, Head, Solid Tumor Service, and Director of the Breast Cancer Research Program at Weill Cornell Medical School said, “It is terrific to see the implementation of targeting metabolism in treating cancer finally underway. I am cautiously optimistic, based on the preliminary safety and efficacy results of BPM 31510 in the phase I in solid tumors, that we will be able to quickly move this agent into phase II trials in selected cancers.”
Future development
Berg Pharma plans to move into Phase II trials in late 2012 with specific focus on cancers that demonstrate an aggressive/highly metabolic phenotype such as pancreatic, triple-negative breast, and colorectal cancers. Pre-clinical models presented at the 2012 AACR meeting showed that BPM 31510 has a synergistic effect with various chemotherapy regimens in aggressive cancers. Niven R. Narain, Co-Founder, President & CTO of Berg Pharma noted “BPM 31510 is showing promising activity in early trials as a monotherapy.” The researchers are planning to assess activity in combination with standard of care.
For more information:
Hendifar AE, Chawla SP, Quon D, Chua VS, Fernandez L, Nagre S, et al.
Phase I study of BPM 31510 in advanced solid tumors: Updated analysis of a novel treatment with promising activity. J Clin Oncol 30, 2012(suppl; abstr 3015)
Session ASCO 2012: Developmental Therapeutics – Experimental Therapeutics
Type: Poster Discussion Session
Time: Saturday June 2, 1:15 PM to 5:15 PM
Location: S405
Discussion Time: Saturday June 2, 4:45 PM to 5:45 PM
Location: S406
Jimenez JJ, Mauro LM, Akmaev VR, McCook J, Du M, Luan S, et al. Effect of BPM 31510 on survival outcomes when used in combination with gemcitabine in a preclinical model of pancreatic cancer. J Clin Oncol 30, 2012 (suppl; abstr e14593)
References: [1]Narain NR, et al., Proceedings of AACR Meeting Abstracts 2011.
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