siRNA Delivery by RONDELTM, a Cyclodextrin-Polymer Based Delivery System: From Benchtop to the Clinics

Helen F. Chuang1, Jeremy D. Heidel1, Joanna Y.-C. Liu1, Ryan K. Zeidan1, Yongchao Liang1, Shyam Rele1, and Mark E. Davis2. (1) Calando Pharmaceuticals, 129 N. Hill Ave Suite 104, Pasadena, CA 91106, (2) Chemical Engineering, California Institute of Technology, Pasadena, CA 91125

Calando Pharmaceuticals is developing a proprietary, targeted siRNA delivery platform, RONDEL™ (RNAi/oligonucleotide delivery), which formulates therapeutic siRNA into targeted nanoparticles. CALAA-01, Calando's lead nanoparticle drug candidate, contains an siRNA targeting the M2 subunit of ribonucleotide reductase (RRM2) for applications in cancer. Extensive characterizations have been performed on the physicochemical properties, in vitro efficacy, and in vivo safety of these nanoparticle formulations. CALAA-01 is currently in a Phase I human clinical trial, representing the first targeted systemic siRNA delivery in the clinics and the only clinical stage RNAi therapeutic oncology program. As a demonstration of the versatility of the RONDEL™ platform, Calando is also developing a second candidate, CALAA-02, which contains an siRNA targeting the hypoxia inducible factor-2 alpha (HIF-2α), for applications in cancer as well. CALAA-02 is currently in pre-clinical development.