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Lodamin for Treating Eye Diseases

Lodamin is a novel anti-angiogenic drug and a non-toxic derivative of TNP-470.


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Lodamin for the Treatment of Cancer

Inventors: M. Folkman, Ofra Ratsaby-Benny

Categories: Therapeutics

SubCategories: Neurology/Neuroscience, Oncology/Hematology, Ophthalmology

Keywords: Anti-angiogenesis

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 had one of the most potent anti-angiogenic activity and 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. Also, the drug had poor oral availability and a short half-life. Dr. Ofra Benny-Ratsaby has developed a formulation, called Lodamin, which potentially solves all these limitations. Lodamin is a conjugate of TNP-470 to PEG and PLA polymers. It 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: Nature Biotechnology. 2008 Jul; 26(7):799-807.

IPStatus: Pat. Pend.

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