Aphios Corporation

Bryostatin 1, 2 and 3

Aphios manufactures natural bryostatin 1, bryostatin 2 and bryostatin 3 from Bugula neritina utilizing its patented SuperFluids™ CXP process [US Patent No. 5,750,709].

Bryostatin 1 is one of a series of cyclic macrolides isolated from the marine bryozoan Bugula neritina (Order Cheilostomata). This arborescent bryozoan is found in temperate and subtropical environments worldwide, but only B. neritina from California and the Gulf of Mexico is known to contain bryostatins 1, 2 and 3 that are characterized by the C- 20 (E,E)-octa-2-dienoate ester (Pettit, 1985).

Bryostatin 1 is in clinical development as an antileukemic agent by the National Cancer Institute in the United States and by the Cancer Research Campaign in Great Britain (Newman, 1995; Philip et al., 1993; and Prendiville et al., 1993). Bryostatin 1 is currently in Phase II clinical trials in the US against melanomas, lymphomas and renal cells (Newman, 1995).

In vitro studies have shown that bryostatin 1 is a potent antileukemic agent that works by a unique and unusual mechanism. This compound exhibits selective activity against leukemias and directly stimulates bone marrow progenitor cells to form colonies that functionally activate neutrophils (Suffness et al., 1989). This combined activity is unusual since most cytotoxic anticancer agents are toxic to bone marrow. The mechanism of activity is unknown, but may be related to the ability of the bryostatins to modulate the protein kinase C receptor. In clinical trials, bryostatin 1 does not appear to have any significant clinical efficacy as a single agent (Pagllaro et al., 2000). Preliminary results from a recent Phase II clinical trial presented at the ASCO meeting in May 2001 suggest that bryostatin 1 increases tumor response rates when used in combination with Taxol® against esophageal cancer. The National Cancer Institute is currently testing bryostatin 1 in combination with other chemotherapeutic agents in clinical trials.

Other potential roles for bryostatin include: (1) use in combination chemotherapy to counteract myelosuppression; (2) use between courses of conventional chemotherapy to stimulate hematopoiesis (Kraft, 1993; and Philip et al., 1993); and (3) therapeutics for Alzheimer's Disease and Cognitive Disorders.