Genaera Corporation announced the results of a Phase 1 clinical trial of squalamine in advanced cancer patients. The research was conducted in collaboration with investigators at the Lombardi Cancer Center at Georgetown University Medical Center. A preliminary report on this study was previously presented at the American Society of Clinical Oncology (ASCO) meeting in May 1999.

The data describes Phase 1 clinical trial designed to investigate the safety of squalamine as a single agent, at increasing doses and over multiple courses of treatment. Of the nineteen (19) patients with advanced cancer to whom squalalmine was administered, transient tumor responses were observed in a patient with synovial cell sarcoma and a patient with breast carcinoma with cutaneous metastases. Dose limiting toxicity was encountered beginning at squalamine doses of 384 mg/m2/day and 538 mg/m2/day and consisted of grade 3 liver transaminase elevations that resolved 3-11 days after ceasing squalamine infusion. On the basis of preclinical evidence of synergy with cytotoxic agents and the demonstration of human safety from this trial, additional clinical trials were initiated with squalamine in combination with cytotoxic chemotherapy for patients with late stage lung cancer and ovarian cancer.

Roy C. Levitt, President and Chief Executive Officer, commented, "Squalamine has demonstrated antiangiogenic properties in multiple clinical trials, both as a single-agent and in combination with standard chemotherapy. We continue to advance the clinical development of this potent small molecule, and feel our progress over the past several years provides a solid basis to move into the next phases of clinical development."

Squalamine is the first clinical drug candidate in a class of naturally occurring, pharmacologically active, small molecules known as aminosterols. Squalamine is a potent antiangiogenic molecule with a unique multi-faceted mechanism of action that blocks the action of a number of angiogenic growth factors, including vascular endothelial growth factor (VEGF).

Squalamine inhibits angiogenesis in tumor and in ocular angiogenesis models by a long-lived, intracellular mechanism of action. The mechanism of action is due to the specific entry of squalamine into activated endothelial cells through membrane invaginations known as caveolae, and subsequent binding and chaperoning of calmodulin to an intracellular membrane compartment. This unique mechanism has three principal antiangiogenic effects on endothelial cells: 1) blockage of cell signals from multiple growth factors including VEGF and bFGF, altering cellular activation and cell division; 2) decreased expression of surface integrin alpha-v-beta-3, altering cell-cell interactions; and 3) altered cytoskeletal structure, decreasing motility.

Genaera announced in November 2001, the commencement of a phase 2b clinical trial designed to test squalamine, an angiogenesis inhibitor, for the treatment of patients with non-small cell lung cancer (NSCLC). This multi-center randomized study will evaluate up to 90 patients receiving weekly dosing of squalamine, combined with weekly chemotherapy of carboplatin and paclitaxel, in patients with Stage IIIB or Stage IV advanced disease. Half of the patients will receive a squalamine dose of 100 mg/m2, and the other half will receive a dose of 200 mg/m2. The optimization in dosing regimen has the potential to yield an improved safety and efficacy profile for the combination of squalamine and the chemotherapy agents in this disease indication.