Biotech Values

[DewDiligence]

Publication on preclinical study of OXGN’s second-generation VTA:

[Not much new here --OXi4503 has been described in this manner by OXGN for a long time. They claim this is a miracle drug that shuts down blood flow *and* kills tumor cells directly, so it will be interesting to see the data when this compound finally gets into clinical testing.

See the following post for the abstract itself. (The link to the abstract in the middle of this PR must be stripped of punctuation in order to work.)]

http://biz.yahoo.com/bw/040506/65467_1.html

>>
OXi4503's Tumor Cell-Killing Mechanism Explored in Peer-Reviewed International Journal of Cancer

Thursday May 6, 9:21 am ET

New Research Highlights OXiGENE's Lead Pre-Clinical Vascular Targeting Agent

WALTHAM, Mass.--(BUSINESS WIRE)--May 6, 2004-- OXiGENE, Inc. (NASDAQ: OXGN, XSSE: OXGN) today announced the publication of a research paper exploring the mechanism by which its lead pre-clinical compound, OXi4503, triggers the collapse of the chaotic network of blood vessels within a solid tumor. The paper, "Combretastatin family member OXi4503 induces tumor vascular collapse through the induction of endothelial apoptosis," appears in the "Early View" online edition of the peer-reviewed International Journal of Cancer (http://www3.interscience.wiley.com/cgi-bin/jissue/76502439). Findings will be published in the journal's print edition in issue 111 (4). The study, conducted in conjunction with scientists from the University of Lund in Sweden and Baylor University in Texas, is important in understanding the sequence of events thought to make tumor vessels vulnerable to this new vascular targeting agent.

The effects of a single dose of OXi4503 (100 mg/kg) on tumor blood flow were studied in a mouse model bearing MHEC5-T hemangioendothelioma. Blood flow in the tumor tissue was reduced to 50 percent one hour after drug administration and to less than 10 percent at six hours. Even at extended periods up to 72 hours, after a single treatment, blood flow had recovered to just 35 percent. [The obvious question: is this a big enough reduction to be therapeutically meaningful?]

"The time course of the tumor vascular response observed with OXi4503 treatment supports this drug for development as a stand-alone therapy, and also lends support for the use of the drug in combination with other cancer therapies," researchers reported.

"These findings further validate the body of pre-clinical data suggesting that OXi4503 holds significant promise as an anti-tumor compound," said Dai Chaplin, Ph.D., OXiGENE's chief scientific officer and head of research and development. "While it is still very early in the evolution of this compound, the insight we have gained into how OXi4503 works will be important as we prepare to embark on its clinical development."

OXi4503 and OXiGENE's investigational drug, Combretastatin A4 Prodrug (CA4P), are small molecule vascular targeting agents designed to cut off blood supply to tumors by changing the shape of the vasculature's endothelial cells.

The International Journal of Cancer research produced several key findings in addition to evidence of blood flow shutdown. For example, researchers said that, compared with the reduction in tumor tissue, blood flow in normal tissue was not significantly affected by OXi4503. This suggests the potential of OXi4503 to selectively target tumor blood vessels.

In addition, researchers noted that the compound increased the permeability of tumor blood vessels, potentially ignited by a sudden release of a substance known as vascular endothelial growth factor (VEGF). Under normal conditions, VEGF causes new tumor blood vessels to sprout and tumors to spread. But when coupled with blood flow shutdown, researchers hypothesized that VEGF-induced changes in vessel permeability following treatment with OXi4503 might actually contribute to the collapse of the tumor vasculature.

Cancer Research UK, the world's largest volunteer-sponsored cancer research organization, is completing pre-clinical toxicology testing on OXi4503 and plans to advance the compound into a Phase I clinical trial in late 2004.
<<