1. Teaching an Old Drug New Tricks:
Utilizing a Novel Formulation of Niclosamide to Treat
Metastatic Osteosarcoma
Gireesh B. Reddy, MSIII
Eward Lab, Department of Orthopaedic Surgery,
Duke University School of Medicine
Consortium for Canine Comparative Oncology (C3O) Symposium
Durham Convention Center
February 23, 2018

2. Challenge: Therapeutic advances for metastatic osteosarcoma have stagnated
MAP ± HDMTX + FA
1970s – HDMTX + VC + FA
Osteosarcoma survival in patients 0 to 24 years old delineated by stage.
Increased incidence, disease progression, and similar histologic and genetic pathogenesis of canine OS enable initial study of potential next-generation chemotherapeutics.
Mirabello L, et al. Cancer. 2009;115(7):

3. NSNPs inhibit human and canine OS growth and downregulate dysregulated OS pathways

4. Solution: Lipid encapsulated niclosamide stearate nanoparticles (NSNPs)
Niclosamide – An old anthelminthic that demonstrates inhibition of Wnt, JAK/STAT3, and Akt/mTOR/S6.
Poor bioavailability limits therapeutic utility outside the gut.
Taking advantage of 1) Increased LDL-R expression in cancer and 2) Hydrophobic packaging capabilities of lipoproteins, we developed a novel lipid nanoparticle formulation of niclosamide stearate (NSNPs).
Specifically the LRP5 Wnt co-receptor
Hoang BH, et al. Int J Cancer. 2004;109(1):
Shrivastava M, et al. Sci Pharm. 2014;82(4):

5. NSNPs slow metastasis progression and prolong survival without treatment-derived morbidity
Mean tumor burden, by treatment
PBS
NSNPs
Dox
Change in weight over time, by treatment
Kaplan-Meier survival curves, by treatment

6. Acknowledgements
Will Eward, DVM, MD David Hsu, MD, PhD Jason Somarelli, PhD David Kerr Kathryn Ware, PhD Erdem Altunel, MD Suzanne DeWitt, DVM Sneha Rao Tim Kreulen Brooke Robbins Terese Camp
David Needham, PhD, DSc
Artak Tovmasyan, PhD
Greg Palmer, PhD
Gabi Hanna, PhD