Out-licensing and Partnering Opportunities
Wnt Therapeutics Program
We are seeking a strategic collaborator to advance the development and commercialization of drug candidates identified as part of our Wnt therapeutics program. Our lead candidate in this program is NU206, a Wnt regulator also known as R-Spondin1 (RSpo1). Our Wnt therapeutics program targets a broad range of indications where cell regeneration and differentiation are important to disease processes, such as gastrointestinal disease, bone disorders, wound healing and cancer.
The Wnt signaling pathway is critical for regulating cell growth and differentiation during homeostasis and pathogenesis. We have developed a comprehensive approach to target key receptors and secreted proteins that modulate the Wnt pathway. In addition, we have produced mAbs and secreted recombinant proteins with biological activity in cellular assays and animal disease models. Potential indications include: Inflammatory Bowel Disease (IBD), peptic ulcers, mucositis, wound healing, and cancer, as well as bone disorders and osteolytic lesions caused by osteoarthritis and multiple myeloma.
Targeting Key Receptors and Secreted Proteins in the Wnt Pathway
The R-Spondin (RSpo) family of secreted proteins are the first biologic agents that can be used to enhance endogenous Wnt signaling in vivo and, therefore, provide therapeutic potential in diseases that are dependent on the Wnt pathway for restoration of homeostasis or tissue repair. RSpo proteins are highly potent therapeutic agents in murine colitis and mucositis models1 and are currently being assessed in additional indications including wound healing, osteolytic lesions and cancer.
RSpo proteins are novel regulators of the Wnt pathway and were first identified by Nuvelo as potent gastrointestinal mitogens in transgenic mice.2 We have recently demonstrated that RSpo proteins regulate the Wnt pathway by antagonizing the Wnt inhibitor DKK1 and subsequently control the cell surface levels of LRP5/6.3 Numerous studies have implicated DKK1 as a key negative regulator in bone remodeling in diseases such as osteoarthritis and multiple myeloma. Therefore, RSpo proteins likely represent exciting therapeutic options to improve bone restoration.
We have a strong intellectual property position and have filed several composition of matter and method of use patent applications claiming several members of the RSpo family of proteins. We have an agreement in place with KIRIN Pharma USA, Inc. related to RSpo1 and we retain control of development and commercialization under this agreement.
In addition to RSpo proteins, we are currently developing mAbs against DKK1 and key receptors in Wnt signaling including LRP6, LRP5 and Frizzled receptors. We have identified a series of mAbs against LRP6 that block DKK1 inhibition.
Wnt Therapeutics: Biologic Pipeline
1. Zhao et al. (2007) R-Spondin1, A novel Intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 132. (http://www.sciencemag.org/cgi/content/abstract/309/5738/1256)
2. Kim et al. (2005) Mitogenic influence of human R-Spondin1 on the intestinal epithelium. Science 309.
(http://www.sciencemag.org/cgi/content/abstract/309/5738/1256)
3. Binnerts et al. (2007) R-Spondin regulates Wnt signaling by inhibiting internalization of LRP6. Proceedings of the National Academy of Sciences in press. (URL not available at this time; contact Dr. Panarites for reprint after September 10, 2007.)