Safety Study of CALAA-01 to Treat Solid Tumor Cancers

CALAA-01 is a targeted nanocomplex that contains anti-R2 siRNA. The complete nanocomplex formulation consists of four components: 1. a duplex of synthetic, non-chemically-modified siRNA (C05C) 2. a cyclodextrin-containing polymer (CAL101), 3. a stabilizing agent (AD-PEG), and 4. a targeting agent (AD-PEG-Tf) that contains the human transferrin protein (Tf). The cationic polymer interacts electrostatically with anionic siRNA to assemble into nanocomplexes below approximately 100 nm in diameter that protect the siRNA from nuclease degradation in serum. The siRNA-containing nanocomplexes are targeted to cells that over express the transferrin receptor (TfR). Upon reaching a target cell, transferrin binds to TfRs on the cell surface and the siRNA-containing nanocomplex enters the cell by endocytosis. Inside the cell, chemistry built into the polymer achieves unpackaging of the siRNA from the nanocomplex, permitting it to function via RNA interference.