Gallium Maltolate A Dual Mechanism for Fighting Cancer Titan’s gallium maltolate is the first gallium containing agent with high oral bioavailability. The product has two distinct potential actions: directly targeting and killing cancer cells, and protecting bone from the effects of tumor metastasis. Iron binds to  ribonucleotide reductase permitting DNA synthesis Gallium inhibits ribonucleotide  reductase and DNA synthesis causing tumor cell death Tumor cell death Iron Gallium Maltolate Gallium “ —— E Fu — _____  " „ a — ae — Gallium maltolate has already been shown to safely provide sustained blood levels of biologically active gallium for the potential treatment of cancer and other diseases. Titan is currently evaluating gallium maltolate in Phase I/II clinical studies in multiple myeloma, metastatic prostate cancer, metastatic bladder cancer and refractory lymphoma. Titan also plans to commence additional studies in bone related disease and other settings. In bone diseases and cancer metastatic to bone, bone resorption (osteoclasts) outpaces bone deposition (osteoblasts), resulting in weakened and damaged bone. Gallium protects bone from such damage by inhibiting bone resorption and stimulating bone deposition. Nine Indication(s) Preclinical Phase 1 Phase 2 Phase 3 Myeloma,  Prostate Cancer, Lymphoma, Bladder Cancer Gallium Maltolate Gallium inhibits osteoclasts, and stimulates osteoblasts Repaired bone Gallium Maltolate Gallium Diseased bone Osteoclast Osteoblasts A key enzyme essential for DNA replication in cancer cells is ribonucleotide reductase, which is active when bound to ferric iron. Gallium concentrates in tumor tissues and by substituting for ferric iron inhibits the activity of ribonucleotide reductase. This action inhibits DNA synthesis and cancer cell growth.