MBFT is developing novel, targeted therapies that are intended to treat a broad range of cancer indications in dogs and cats. Each of our development products is supported by extensive preclinical studies in animal models and safety and efficacy studies in human clinical trials.
Our goal is to commercialize effective and humane products that address the underlying causes of disease and that will put patients into long-term remission. Our products will be provided in simple-to-administer formulations to maximize pet owner convenience and compliance over the course of treatment.
MBFT-101 is a targeted, broad-spectrum Polyamine-Based Therapy (PBT) combination therapy consisting of di-fluoro-methyl-ornithine (DFMO) and the polyamine transport inhibitor, MBF-1569. This drug combination is believed to have broad spectrum activity against numerous forms of solid tumors, including sarcomas and a variety of epithelial tumors.
MBFT-101 acts by starving rapidly growing neoplastic cells of polyamines, which are essential for DNA replication, cell cycle regulation and cell growth, resulting in tumor shrinkage and eradication.
MBFT-101 targets the two critical sources of polyamines:
- DFMO specifically and irreversibly inhibits ODC, the key biosynthetic enzyme that converts ornithine to putrescine and is upregulated in tumor cells; and
- MBF-1569 prevents uptake of polyamines from the intercellular tumor environment. This dual-targeting mechanism effectively starves the tumor cells but is not deleterious to normal cells.
MBFT is collaborating with Dr. Thomas O’Brien, a leading expert on polyamine and cancer at the Lankenau Institute for Medical Research (LIMR) on product development and clinical evaluation. The first pilot study underway at the University of Pennsylvania’s School of Veterinary Medicine is evaluating MBFT-101 as a treatment for feline non-resectable oral squamous cell sarcoma (SCC), an aggressive cancer and the most common feline oral tumor type. The prognosis in cats with oral squamous cell carcinoma is very poor because of the rapid growth and advanced stage of the disease by the time of diagnosis (Maretta 2001). Extensive studies of PBT therapy by Dr. O’Brien and collaborators have demonstrated the effectiveness of DFMO and polyamine transport inhibitors, producing complete tumor responses and durable cures in proof of principle studies with squamous cell carcinoma.
Chen, Y., et al (2006) Int J Cancer. 118:2344-9
Burns et. 2009. J. Med. Chem. 52 (7), 1983-1993
MBFT-102 is under development as a DNA-based immunotherapy for dogs mediated through the tumor suppressor/cytokine protein mda-7/IL-24. mda-7 (melanoma differentiation-associated gene-7; approved gene symbol IL24) was identified at Columbia University as one of several genes up-regulated during terminal differentiation of melanoma cells. Studies using plasmid-based or adenoviral vector-mediated delivery of mda-7 confirmed that de novo MDA-7 protein expression reduced growth and colony formation in a variety of human cancer types including melanoma, glioblastoma multiforme, osteosarcoma, and carcinomas of the breast, cervix, kidney, colon, lung, nasopharynx, and prostate. No effects on normal cells were observed. Many anti-tumor properties of mda-7 have been studied, including down-regulation of oncogenic and upregulation of tumor suppressor pathways, cell cycle arrest, inhibition of tumor cell invasion and metastasis, and antiangiogenic effects.
The mda-7 gene has been evaluated in human patients by Introgen, Inc., which conducted an open-label Phase I dose-escalation trial on 22 advanced cancer patients with a variety of cancers, including melanoma, breast, colon, head and neck, lymphoma, hepatoma and adrenal carcinoma. The patients received intratumoral injection of the Introgen’s human-specific product INGN 241, a nonreplicating adenovirus vector carrying the mda-7 transgene. Treatment was generally well-tolerated and durable clinical responses were observed in a subset of patients who received multiple intratumoral injections. The human trial results indicate that mda-7 is a promising immunotherapy therapeutic that can generate direct tumor growth inhibition and can act at distal tumor sites through a bystander anti-tumor effect.
MBFT is adapting this potent, broad-spectrum solid tumor therapy to canines.
Lebedeva I., et al. mda-7/IL-24, novel anticancer cytokine: Focus on bystander antitumor, radiosensitization and antiangiogenic properties and overview of the phase I clinical experience (Review) Int J. Oncology 31: 985-1007, 2007