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CMCC 1601

Lodamin for the Treatment of Cancer

Inventors: M. Folkman, Ofra Ratsaby-Benny

Invention Types: Therapeutics

Research Areas: Neurology/Neuroscience, Oncology/Hematology, Ophthalmology

Keywords: Anti-angiogenesis, Composition of Matter, Small Molecule/Drug

Related Cases: 1810, 1855

For More Information Contact:  Dietz, Ryan

 

Invention Description:

Originally identified in the late Dr. Judah Folkman's laboratory, TNP-470 is a low molecular weight synthetic analogue of Fumagillin, a product secreted by a fungus. It was one of the most potent anti-angiogenic compounds and possessed the broadest anti-cancer spectrum of any known agent. TNP-470 showed promise in oncology development but Phase II trials were interrupted because of reversible neurotoxicity, poor oral availability and a short half-life.


Dr. Ofra Benny-Ratsaby has developed a formulation, called Lodamin, which potentially solves all of these limitations. Lodamin is a conjugate of TNP-470 to PEG and PLA polymers and forms micelles with TNP-470 at its core, allowing for oral availability and for delivery to the tumor where the drug is slowly released. Lodamin exhibited anti-angiogenic activity in vivo and inhibited primary tumor growth in mouse models of melanoma, lung, breast, brain and ovarian cancers by more than 80% without neurotoxicity or other adverse events. Importantly, Lodamin also prevented melanoma-derived liver metastases, a condition which is incurable in humans, and prolonged survival in mice.

Applications:

These in vivo results indicate that Lodamin could be a clinically useful angiogenesis inhibitor with potential broad treatment applications in angiogenesis-dependent diseases such as cancer, endometriosis, obesity, macular degeneration, alone or in combination with other anti-angiogenic agents or with chemotherapy.

Competitive Advantages:

• Lodamin is the first oral non-toxic derivative of TNP-470: MetAp2 inhibitor
• Expected to be safe: no crossing of blood brain barrier; no observed neurotoxicity, weight loss or tissue abnormalities; polymers are biocompatible, nonimmunogenic and FDA approved
• Prevents liver metastases without liver toxicity, and prolongs survival
• Improved potent anti-cancer efficacy due to preferential accumulation in tumor tissue, slow release and long blood circulation time of at least 72hrs
• Potential treatment for indications beyond oncology: inhibited lesion size by 71% in a mouse model of macular degeneration when administered orally
• Inhibits both capillary growth and leakage of fluid
• Several hundred patients treated with parent molecule TNP-470
• Composition of matter and method of use claims pending

Business Opportunity:

Exclusive license available

Key Publications: • Becker CM, et al. Circulating endothelial progenitor cells are up-regulated in a mouse model of endometriosis. Am J Pathol. 2011 Apr;178
• Benny O, et al. An orally delivered small-molecule formulation with antiangiogenic and anticancer activity. Nat Biotechnol. 2008 Jul;26(7)

2 issued US patents and other pending and allowed in foreign jurisdictions

IPStatus: Patented