Caplostatin, a novel anti-angiogenic polymeric drug
Inventors: M. Folkman, Ronit Satchi-Fainaro
Invention Types: Therapeutics
Research Areas: Oncology/Hematology
Keywords: Anti-angiogenesis, Composition of Matter, Small Molecule/DrugFor More Information Contact: Dietz, Ryan
Originally identified in 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 early oncology clinical development, but Phase II trials were interrupted because of reversible neurotoxicity. Dr. Folkman's group have since conjugated TNP-470 with a water-soluble HPMA polymer, yielding a new molecule named Caplostatin. Compared to TNP-470, it has an increased anti-angiogenic activity against a variety of cancers, for example 88% reduction in melanoma growth rate and 86% inhibition of Lewis lung carcinoma growth in vivo, without affecting neurological functions. Additional work showed synergistic inhibition of colon and prostate cancers and melanoma and gliobastoma in mouse models when Caplostatin was combined with Avastin.
These in vivo results indicate that Caplostatin could be a clinically useful angiogenesis inhibitor with potential broad treatment applications in angiogenesis-dependent diseases such as cancer, endometriosis, obesity, macular degeneration and diabetic retinopathy, alone or in combination with other anti-angiogenic agents or with chemotherapy.
- Expected to be safe: no crossing of blood brain barrier, no observed neurotoxicity or weight loss, and polymer is biocompatible, nonimmunogenic and nontoxic
- Improved potent anti-cancer efficacy due to
o Selective targeting to tumor vessels because of polymer properties
o Prolonged exposure to endothelium: increased circulation time, accumulation at sites of proliferating endothelial cells, increased (water) solubility
- Synergistic anti-cancer activity with Avastin
- Potential treatment for indications beyond oncology
o Suppressed growth of endometriotic lesions by 59% in mouse model (Folkman group)
- Actively researched in the field: over 500 published articles to date on TNP-470 and Caplostatin
- Several hundred patients treated with parent molecule TNP-470
- Composition of matter and method of use patents issued in certain jurisdictions
Exclusive license available
Key Publications: Nature Medicine 2004 10(3): 256
Cancer Cell. 2005, 7(3): 251
Amer. J. Pathol. 2006, 168 (6): 2074.
Related Publications: Issued US patents 6,949,584 and 7,332,523
Issued AUS patent 2003230852
Additional pending US and foreign applications