NU206
Potential Therapeutic Applications |
Clinical Trials
Commercialization Rights |
Scientific Publications and Presentations
A Wnt Pathway Modulator
NU206 (R-spondin1) is a recombinant, secreted protein that acts as a key regulator of the Wnt pathway, the critical pathway that stimulates cell growth and differentiation during homeostasis and pathogenesis in specific tissues including the GI epithelium and bone. NU206 works by antagonizing an inhibitor of the Wnt pathway, DKK1, thereby turning on the pathway. Preclinical studies suggest it can promote growth and repair in animal models of radiation or cancer chemotherapy induced GI injury, inflammatory bowel disease, bone disease and wound healing. In animal models of GI disease, the effect of NU206 was transient and reversible in normal tissue. Once administration of NU206 is stopped, the epithelium of the intestine reverts to its normal state and does not continue to proliferate.
Potential Therapeutic Applications
Potential therapeutic indications include treatment of gastrointestinal diseases, including cancer therapy induced mucositis and inflammatory bowel disease, in addition to bone disease and wound healing.
In preclinical studies, NU206 was shown to improve the healing of GI epithelial tissues and diminish symptoms of inflammatory bowel disease and mucositis, including rectal bleeding, stool quality, diarrhea and weight loss.
Clinical Trials
We began a Phase 1 single ascending dose (SAD) trial in healthy volunteers in July 2008 and expect data from the trial in the second half of 2008. We also plan to initiate a Phase 1b multiple ascending dose trial in healthy volunteers in the fourth quarter of 2008 or first quarter of 2009.
The information we gather from these two healthy volunteer trials will provide useful insight for the multiple indications we plan to investigate.
Commercialization Rights
In April 2005, we entered into a collaboration agreement with Kirin Pharma Company, Ltd. for the development and commercialization of NU206. Under the terms of the agreement, Nuvelo received a $2.0 million up-front cash payment from Kirin. Nuvelo leads worldwide development, manufacturing and commercialization of the compound and all operating expenses and profits related to the development and commercialization of NU206 are shared 60% (Nuvelo)/40% (Kirin).
Scientists from Nuvelo and Kirin worked together to identify and characterize NU206 as part of a longstanding collaboration focused on the discovery of novel, secreted proteins. NU206 is the first compound to move into the clinic from this program.
Scientific Publications and Presentations
Scientific Publications
Kim KH, Wagle M, Tran K, Zhan X, Dixon M, Liu S, Gros D, Korver W, Yonkovich S, Binnerts M, Abo A. The RSpo protein family regulates the Wnt pathway by a common mechanism. Mol Biol Cell 2008;Apr 9 [epub ahead of print]
Binnerts ME, Kim KA, Bright JM, Patel SM, Tran K, Bouchard A, Zhou M, Leung JM, Lomas WE 3rd, Dixon M, Hazell SA, Wagle M., Nie WS, Tomasevic N, Willams J, Zhan X, Levy M, Funk W, Abo A. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci USA. 2007;104:14700-14705.
Zhao J, De Vera J, Narushima S, Beck EX, Palencia S, Shinkawa P, Kim KA, Liu Y,
Levy M, Berg DJ, Abo A, Funk WD. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology. 2007; 132:1331-1343.
Kim KA, Zhao J, Andarmani S, Kakitani M, Oshima T, Binnerts ME, Abo A, Tomizuka K, Funk WD. R-Spondin proteins: a novel link to beta-catenin activation. Cell Cycle. 2006;5:23-26.
Abraham C, Cho JH. Inducing intestinal growth. N Engl J Med. 2005;353:2297-2299.
Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. Mitogenic influence of human R-Spondin1 on the intestinal epithelium. Science. 2005;309:1256-1259.
Scientific Presentations
Zhao J, Kim K, Abo A. R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis by activating canonical Wnt/Β-catenin pathway.
American Association for Cancer Research (AACR) Annual Meeting, April 2008, San Diego, CA.
Zhao J, Palencia S, De Vera J, Kim K-A, Beck E, Aguilar G, Liu Y, Emtage P, Abo A, Funk W. R-Spondin1, a novel intestinotrophic mitogen, reduces chemotherapy and radiotherapy-induced intestinal mucositis in mice. American Association for Cancer Research (AACR) Annual Meeting, April 2006, Washington, DC. [Zhao J et al AACR Meeting Abstracts, 2006:710 - 711.]