Biotech Values

[nuere]

OXGN

Good summary of the VDA space picked up by Kosar legolas. Hope you don't mind if I highlight the OXGN part

By Randall Osborne

West Coast Editor
Roche's loss became Novartis' gain - maybe - in the increasingly
competitive cancer space occupied by vascular disrupting agents
(VDAs), where Antisoma plc holds a strong position.

Less than a year after losing partner F. Hoffman-La Roche Inc. for
AS1404, Antisoma is getting $75 million up front in a licensing deal
with Novartis AG and $25 million more when Phase III lung cancer
trials with the VDA start early next year.

Antisoma's shares (LSE:ASM) rose £4.75 (US$9.50) Thursday, or 9
percent, to close at £57.25.

Longtime partner Roche, of Basel, Switzerland, declined to take AS1404
into Phase III trials and cited "commercial reasons" - most likely
referring to the 2011 expiration tag on the compound's composition-of-
matter patent in the U.S. - and London-based Antisoma promised an "eye-
watering" deal for the compound on the way in December, when the firm
had less than six months of operating cash.

The deal has arrived. Novartis, also of Basel, could provide as much
as $890 million in milestone payments, along with royalties, and will
fund all future development as well as Phase II trials now under way.

Antisoma retains right to co-commercialize the flavonoid AS1404, which
"has been bumped around a little bit," and could be hampered by the
patent expiry, noted Kobi Sethna, president and CEO of San Diego-based
Nereus Pharmaceuticals Inc., an earlier-stage VDA player.

Nereus has NPI-2358, one of about 200 synthetic analogues made after
finding the activity and novel chemistry from a marine fungal extract.
A Phase I trial against solid tumors launched last summer. "The patent
life on our compound is just starting," Sethna said.

Plans for Antisoma's AS1404 include the Phase III study in squamous
non-small-cell lung cancer, and supporting studies in lung and other
cancers. If Phase II data merit, the compound will move into Phase III
trials in prostate and ovarian tumors, too.

Unlike anti-angiogenesis drugs, which block formation of tumor blood
vessels, VDAs target vessels already established, causing endothelial
cells to collapse.

"The tumor is eaten away, from the inside out," Sethna said, adding
that VDAs have been around for "quite a long time. The first
generation came on the scene maybe 12 or 15 years ago, but they had
some liabilities, in terms of fairly significant cardiotoxicity. For a
fair amount of years, these drugs were not looked on favorably."
London-based AstraZeneca plc discontinued work on its VDA known as
ZD6126.

Second- and third-generation products look much better than first
versions, Sethna said, and "the Antisoma compound is reasonably
clean." Nereus' drug, at least in preclinical work, appears safe for
the heart as well as the central nervous system, he said.

"Our compound is slightly different, inasmuch as - based on
preclinical data - we see dual action," Sethna told BioWorld Today.
"It not only disrupts tumor blood flow but seems to have a direct
effect on tumor cells. We've seen some single-agent activity in some
models, as well as very good activity in combination [with chemo and/
or radiation]." NPI-2358 also appears to boast a long duration of
action as it disrupts blood flow, he said.

Others with VDAs in the works include Oxigene Inc., of Waltham, Mass.,
with CA4P (combretastatin A4 phosphate). Paris-based Sanofi-Aventis
Group has the combretastatin derivative AVE8062 in Phase I trials, but
Oxigene's compound is ahead, proving effective last year in Phase II
trials against thyroid cancer, with chemo and without. In February,
CA4P yielded positive Phase II data against myopic macular
degeneration, and Oxigene likely will unveil full ophthalmic data
during a scientific meeting in May.

Meanwhile, the firm is putting the final touches on a Phase III study
with CA4P in anaplastic thyroid cancer, with first dosing expected in
the second quarter of this year. The trial is likely to test CA4P when
combined with chemo agents, as compared to chemo alone, in 100 to 200
patients.

Data from a Phase Ib trial with CA4P plus the approved VEGF inhibitor
Avastin (bevacizumab), from South San Francisco-based Genentech Inc.,
should become known in the third quarter of this year, and positive
results would lead to a Phase II study testing a quadruplet combo
regimen against NSCLC in the second half. CA4P's Phase II ovarian
cancer trial still is enrolling patients.

Also in the VDA pool is Myriad Genetics Inc., of Salt Lake City, which
started the first Phase II trial with Azixa for brain cancer in March.
Azixa, like Nereus' drug, is believed to work as a cytotoxin and VDA.
The first stage of the Azixa study will include about 16 patients.

MediciNova Inc., of San Diego, has MN-029 ready to start Phase II/III
studies in ovarian and NSCLC and are expected to start by the end of
this year. The VDA came from Oxford, UK-based Angiogene
Pharmaceuticals Ltd., which holds a worldwide license.

Abbott, of Abbott Park, Ill., has the sulfonamide ABT-751 in Phase II
trials for lung, colon, breast and kidney cancers. "They don't call it
by [the VDA] nomenclature, but that's how it works," Sethna said.

Adelaide, Australia-based Bionomics Ltd. is doing preclinical work
with the VDA known as BNC105. "It's taken a long time for these drugs
to be accepted, but this whole class is going to get a lot of
recognition," Sethna said

http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bio...