HIV Aids - High hopes - Tustin firm has a drug for cancer, and HIV, too

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High hopes - Tustin firm has a drug for cancer, and HIV, too

cjgaddy

2005-07-24, 5:49 pm

Pray that Tarvacin works in humans as it has in primate tests.
Virologist and HIV-researcher Dr. Preston Marx is involved with the
testing of this novel anti-viral drug.

Sent: Sunday, July 17, 2005 11:08 AM
To: 'grants@cancer.org'; 'mail@hepatitiscsociety.com';
'publisher@hivandhepatitis.com'; 'info@hivforum.org'
Subject: Wolfson Article on Thorpe/Tarvacin 7-16-05

"High hopes - Tustin firm has a drug for cancer, and HIV, too -
maybe."
By BERNARD J. WOLFSON, The Orange County Register, July 16, 2005
http://www.ocregister.com/ocr/2005/...icle_599388.php

What if someone told you they had a drug that could fight cancer and
nearly every human virus from HIV to Hepatitis C, and from Ebola to the
common flu? You might be a little surprised, a little curious, a
little excited -- and more than a little incredulous. But Peregrine
Pharmaceuticals, a small Tustin company, is making a big bet on a new
drug that it says could be just such a panacea.

The drug, Tarvacin, is in the early testing stages. So far, it has
shown promising results against cancer in mice and against at least two
viruses, including one that causes a kind of hemorrhagic fever related
to the deadly Ebola.

Peregrine recently received federal approval to begin initial testing
of Tarvacin in humans for solid tumors and for Hepatitis C. It's also
being tested at lower trial levels -- not on humans -- against the HIV
virus, which causes AIDS, and many others.

A government agency recently asked Peregrine for permission to test the
drug against some 30 viruses considered to be potential agents of
bioterror. The company hopes those tests could lead to early approval
of Tarvacin for use in the case of a bioterror attack -- a move that
would make the drug an earner before it got formal approval from the
U.S. FDA for wider distribution.

Executives at Peregrine know it's still early. But they think -- and
hope -- that they might just be on to something big. When they ponder
the best-case scenario, they get stars in their eyes -- and more than a
few dollar signs.

"This could be the biggest science discovery of my lifetime if it works
against all these viruses and cancer at the same time," says Paul
Lytle, Peregrine's CFO. "If you went out and tried to develop vaccines
for all these viruses, it could take hundreds of years." When Lytle and
his colleagues think of role models, they point to Genentech Inc. in
South San Francisco, whose pioneering anti-cancer drug Avastin has
posted sales of $640 million since its approval early last year.

"You want to model yourself on the people who have been successful,"
says Steven King, Peregrine's CEO. If the early claims about Tarvacin
are borne out, he sees no reason Peregrine couldn't be catapulted from
money-losing research mode into the pharmaceutical big leagues.

"I see that as a way the market has actually responded to a product
such as the one we're developing," King says. "I think Tarvacin
represents what could be termed a blockbuster type drug." Scientists
who are working on the drug with Peregrine are also excited, but they
urge caution. They warn that hypotheses often crumble in the laboratory
for reasons that weren't even imagined beforehand -- and that tests in
humans don't always turn out the way they did in animals.

"There are no guarantees, but it's an interesting idea and it looks
promising," says Preston A. Marx, a virologist at the Tulane Univ.
Primate Center in Covington, La., who's working as a paid consultant to
Peregrine. "There's a lot of additional work until you realize this."
Philip E. Thorpe, a professor of pharmacology at the Univ. of Texas
Southwestern Medical Center in Dallas and a paid Peregrine consultant
-- whom executives at the company call "the father" of Tarvacin --
notes that recent tests of the drug in mice have shown almost complete
abolition of cancer growth and metastasis. But "we need to demonstrate
efficacy in humans," he says.

The reason Tarvacin appears to have such a broad range of uses is that
it targets not any specific cancer or virus, but rather a substance
found in the membranes of all cells. When cells become malignant, or
are infected by a virus, the substance -- known as a phospholipid --
moves from the inside of the membrane to the outer surface, allowing
Tarvacin to bind with it.

The binding marks the cell, raising a red flag that alerts the immune
system to the presence of a foreign body. With viral infections, the
body's white blood cells attack the viruses. With cancer, the immune
system appears to destroy the blood vessels of a tumor, depriving it of
the nutrients it needs to grow.

"The concept is almost so simple it's hard to believe no one picked up
on it before," says King, the CEO.

In cancer, Tarvacin might prove particularly effective in combination
with chemotherapy and radiation, Thorpe says. That's because those more
traditional treatments appear to enhance the movement of phospholipids
to the surface of the membrane, giving Tarvacin a bigger target.

Scientists say Tarvacin could have an advantage over other anti-viral
drugs, because viruses probably won't be able to evade it by mutating.

"Mutation won't affect it because it's targeting a substance which is
not intrinsic to the virus itself but to the host cell -- so that
substance will be there no matter what new form the virus takes," says
Stephen M. Smith, a paid Peregrine consultant and chief of infectious
diseases at the Seton Hall school of Graduate Medical education in New
South Orange, NJ.

Peregrine executives say that even if Tarvacin doesn't pan out, there
are still other lines of business that could help make the company
profitable.

They are fairly far along with testing of Cotara, a drug that has shown
some effectiveness against a certain type of brain tumor. And they
receive royalties from the licensing of intellectual property to other,
more established drug firms.

In addition, Peregrine's wholly owned manufacturing subsidiary, Avid
Bioservices, has a contract to produce an eye drug for another company
-- a deal that could mean significant new revenue.

But clearly, Tarvacin is the 800 pound gorilla in Peregrine's board
room these days. And while company executives soak in the headiness of
a potentially revolutionary new discovery, the scientists are
whispering in their ears a mix of excitement, caution and good
old-fashion scientific curiosity.

"I don't know where it's going to lead us, but the approach is clearly
unique," says Seton Hall's Smith. "As I tell my fellows, empiricism
rules.

But from a theoretical point of view, it's really fun to think about."

= = = = = article end = = = = = = = = = = =
Dr. Philip Thorpe's Lab and the NIAID/NIH take DEAD AIM on ALL
ENVELOPED VIRUSES (ex: Hep/B+C, Influenza, Pneumonia, SARS, HIV/AIDS,
Ebola, Marburg, Lassa) with Anti-Phospholipid Therapy (APT) agents,
like Anti-PS/3G4/Tarvacin, which are "surprisingly effective in
inhibiting the entry, replication and the spread of viral
infections."

A phase1 human trial for All-Solid-Cancers began enrolling at the
Arizona Cancer Center 6-10-05 (possibly 1st patients treated, we
don't know), and the phase1 human trial for Hepatitis-C was approved
by the FDA 5-31-05 and should begin before the end of July - we're
waiting on an announcement of the Site.

Do a GOOGLE on "preston marx" (http://tinyurl.com/8fnex ). This
virologist has joined Thorpe's SRB, and no doubt will be pushing to
test Tarvacin for HIV/AIDS in humans. Remember, Tarvacin attacks
All-Enveloped-Viruses (which is 90% of all viruses).

And: http://www.investorshub.com/boards/...p?board_id=2076

Tarvacin ALL SOLID CANCERS Phase1 status:
6-10-05 Enrollment Initiated at Arizona Cancer Center:
"will enroll up to 28 patients with advanced solid tumors that no
longer respond to standard cancer treatments. Patients who demonstrate
an objective response may be offered continued treatment on an
extension protocol."

http://ir.peregrineinc.com/phoenix....ticle&ID=719219

Tarvacin HEPATITIS C Phase1 status:
5-31-05 HEP-C IND approval:
"a phase1 dose escalation study designed to evaluate a single
intravenous infusion of Tarvacin in up to 32 patients with chronic HepC
virus (HCV) infection... who have failed to respond or who have
relapsed after the current std. treatment with pegylated interferon
plus ribavirin."

http://ir.peregrineinc.com/phoenix....ticle&ID=714919

"Anti-PS/3G4 is the cleanest tumor vessel marker of which we are
aware."

"Since 3G4 attacks viruses indirectly, 'via host physiology, not
the viral genome', viral resistance is much more difficult to
achieve." [big issue for AIDS].

"The antigenic grail, which Thorpe believes it may have found in the
form of phosphatidylserine [PS] - is a marker that is expressed on
blood vessels in all solid tumors and not on blood vessels in normal
tissues."

"The beauty of this macrophage-mediated synergistic approach is that
it should specifically target and starve any solid tumor fed by the
blood stream, including emerging metastases."

"Practically none of the lungs have any sign of disease [3G4 +
Docetaxel combo]. It's quite impressive."

"Tarvacin alone is relatively non-toxic. In a cynomolgus monkey
safety study intended to gauge toxicity, even at 10 times the
anticipated maximum therapeutic dose (1 mg/kg) given repeatedly, there
were no signs of adverse effects."

"If you look at the 3G4 slide, you'll see, most remarkably, that it's
absolutely chock full with macrophages. There are so many of them that
they're beginning to outnumber the tumor cells. So you can see the
reaction that's being mounted against the tumor".

"3G4 + Radiation reduces lung cancer tumor growth by 95%. 3G4 +
Gemcitabine decreased primary tumor growth by 60% and essentially
stopped metastasis to liver and lymph nodes. Data is significant as it
about to begin dosing trials of Tarvacin that allows for patients
presenting with any solid tumor type."

"Here, rodents were infected with Lassa Fever virus, a very lethal
virus; of the animals were getting Tarvacin, half the animals rejected
the virus and went on to live normally. That's an extraordinary result,
I don't know of any other antiviral agent that is known to protect
against Lassa Fever. And we've also shown similar results in
cytomegalovirus."

"Since Tarvacin targets a basic, universal property of enveloped
viruses that is host-derived and independent of the viral genome, it
may be effective against a broad spectrum of enveloped viruses. This
target may also be difficult for viruses to overcome via resistance
mechanisms."

"The pre-clinical data demonstrate that Tarvacin/3G4 and related
Anti-Phospholipid Therapy agents have anti-viral therapy which, if
proven out in the clinic, has far reaching implications for the
treatment of infectious disease... what is particularly exciting about
these initial findings is that the recognition of viral particles by
Tarvacin (3G4) is dependent on a structural component believed to be
universal to all enveloped viruses, giving it the potential to be a
broad-spectrum treatment. It is also a property that is determined by
host physiology, not the viral genome, making viral resistance much
more difficult to achieve."

"When Drs. Preston Marx & Steven Smith they saw the 3G4 animal data
they basically said 'You don't need to treat any more animals, you
need to get this into the clinic as soon as possible.' And that's
what we're doing. So stay tuned for future results regarding
Tarvacin's anti-viral potential."

"The conclusions with Tarvacin are that it has a unique mechanism of
action, there's nothing else like it out there; it homes specifically
to tumor blood vessels and induces white blood cells to attack the
tumor. And, as we looked, it enhances the anti-tumor activity of
chemotherapy drugs, several drugs, I've not shown you all of those, and
also radiation. And it causes no toxicity in monkeys, rodents or
atheroslerotic rabbits treated with the calculated therapeutic dose".

"In mice and monkey tests, we've never seen any sign of toxicity;
about 14 species treated with the therapeutic dose - and that's
thousands of mice and monkeys. And that's even if you increase the
dose to 10x the therapeutic dose."

"The invention is not limited to the treatment of enveloped viruses
alone, nor to any particular virus, which is an important advantage."

"The 3G4 antibody has enormous potential as a broad spectrum
anti-viral agent."

"The 3G4 antibody thus possesses the combined properties of an
anti-angiogenic, anti-tumor vascular and anti-viral agent. The
inhibitory activities of 3G4 on cell division, angiogenesis, tumor
growth and viral infectivity, taken together with lack of apparent
toxicity, show broad therapeutic indications for this antibody,
including in the treatment of angiogenic disorders, cancer, diabetes
and viral infections."

"The anti-viral methods and uses of the invention are suitable for
treating all viruses... as exemplified by treating CMV, RSV, arenavirus
and HIV infections, and the diseases hepatitis, influenza, pneumonia,
Lassa fever and AIDS."

"The 3G4 antibody has also been administered to monkeys in safety
studies and no side effects have been observed."

"The 3G4 antibody thus possesses the combined properties of an
anti-angiogenic, anti-tumor vascular and anti-viral agent. The
inhibitory activities of 3G4 on cell division, angiogenesis, tumor
growth and viral infectivity, taken together with lack of apparent
toxicity, show broad therapeutic indications for this antibody,
including in the treatment of angiogenic disorders, cancer, diabetes
and viral infections."