Biodefense



EMERGENT BIOSOLUTIONS TO
DELIVER 45 MILLION DOSES OF
ANTHRAX VACCINE TO US
GOVERNMENT
Emergent BioSolutions Inc. said in
October 2011  that the U.S.
government is formally ordering 44.8
million doses of the company's
BioThrax anthrax vaccine in an
agreement worth as much as $1.25
billion over five years.

Initial deliveries under this award are
expected to commence in 2011 with
8.5 million doses scheduled to be
delivered during the first contract year.
Deliveries are scheduled to continue,
subject to availability of funding,
through September 2016.  



VACCINE ST-246 MAY END THE
THREAT OF SMALL POX
In the event of a smallpox outbreak,
people around the world would be
saved by an orange and black antiviral
capsule. The antiviral drug, ST-246, is
the brain child of SIGA Technologies,
Inc., and its Chief Scientific Officer,
Oregon State Professor of
Microbiology Dennis E. Hruby.

The FDA is in the midst of approving
ST-246, which Hruby expects to be
completed anywhere in the next 18 to
24 months.

Upon approval, the smallpox antiviral
will be purchased from SIGA by the
Defense Department and added to the
Centers for Disease Control and
Prevention's Strategic National
Stockpile.

ST-246 would be held at trauma
centers and hospitals in case of an
emergency outbreak. SIGA hopes to
market the capsule internationally as
well.

SIGA's groundbreaking drug, ST-246,
is an oral therapeutic agent active
against orthopoxviruses including
smallpox.

It is the only drug from any source ever
to have demonstrated efficacy in non-
human primate models of orthopox
virus disease, which was a requirement
of the request for proposal that
resulted in the current contract.

ST-246 will be the first entirely new
small-molecule drug delivered to the
Strategic National Stockpile under
Project Bioshield. Smallpox, even
though no longer present naturally in
the environment, is considered a
formidable bioterrorism threat, and
there is currently no FDA-approved
treatment for symptomatic individuals.  

ST-246 works by blocking the ability of
the virus to spread to other cells,
preventing it from causing disease.
The FDA has designated ST-246 for
"fast-track" status, creating a path for
expedited FDA review and eventual
regulatory approval.



CMX001 FROM CHIMERIX
SIGA's rival, Chimerix's lead product
CMX001 is being developed as a
broad spectrum antiviral with particular
emphasis on the ability to treat
immunocompromised patients, which
includes individuals infected with
smallpox.

CMX001 is being developed as a
potential broad spectrum oral antiviral
for the treatment of life-threatening
double-stranded DNA (dsDNA) viral
diseases, including herpes viruses,
adenoviruses and orthopox viruses.

The growing body of evidence of
CMX001’s antiviral activity against all
five families of dsDNA viruses that
cause morbidity and mortality in
humans, including smallpox, has
strengthened the compound’s potential
as a dual-use product prescribed as a
traditional pharmaceutical and
stockpiled as a biodefense
countermeasure.

More than 500 patients have been
dosed with CMX001 to date in ongoing
placebo-controlled clinical trials and in
open-label treatment protocols for the
prophylaxis, preemption and treatment
of dsDNA viral diseases.

250 patients have received CMX001
under Emergency Investigational New
Drug Applications (EINDs), including
for treatment of orthopox viruses. A
significant number of the individuals
receiving CMX001 in human testing
have been immunocompromised as a
result of disease or
immunosuppressing therapies
associated with stem cell or solid organ
transplantation.

Clinical studies of CMX001 include: an
ongoing Phase 2 study of the
prevention/control of cytomegalovirus
(a herpes virus) in adult hematopoietic
stem cell transplant patients (CMX001-
201); a Phase 2 study currently being
initiated for the treatment of
adenovirus infection in pediatric and
adult hematopoietic stem cell
transplant patients (AdV HALT
Trial/CMX001-202); and an ongoing
open-label study (CMX001-350) for the
treatment of numerous dsDNA viral
infections.



ACHAOGEN DEVELOPING  NEW
ANTIBIOTIC  AGAINST PLAGUE AND
TULAREMIA
Achaogen, a biopharmaceutical
company in South San Francisco is
developing innovative antibiotics to
treat life-threatening, multi-drug
resistant (MDR) bacterial infections.
Achaogen  has a contract with the
Biomedical Advanced Research and
Development Authority (BARDA),  in
the U.S. Department of Health and
Human Services.
The contract covers development of  
Achaogen’s lead antibiotic candidate
ACHN-490 for the treatment of certain
biothreat agents, including Yersinia
pestis, which causes bubonic plague,
and Francisella tularensis, which
causes tularemia.
Other  life-threatening conditions
included  such as complicated urinary
tract infections and hospital-acquired
pneumonia.

ACHN-490 has been chemically
engineered to retain activity against
bacteria resistant to carbapenems,
cephalosporins, fluoroquinolones,
tetracyclines, and legacy
aminoglycosides.

ACHN-490 Injection is being
investigated in a randomized, double-
blind, comparator-controlled Phase 2
clinical study for the treatment of
complicated urinary tract infection
(cUTI), the most commonly treated
hospital infections in the U.S., and
acute pyelonephritis. Subsequent
clinical studies are being considered to
evaluate ACHN-490 Injection for
hospital-acquired pneumonia (HAP),
ventilator-associated pneumonia
(VAP), complicated intra-abdominal
infections (cIAI) and blood stream
infections (BSI).



NEW COMPOUNDS SHOW PROMISE  
AGAINST DEADLY EBOLA, MARBURG
VIRUSES
US scientists have discovered that two
compounds from a family known as
antisense phosphorodiamidate
morpholino oligomers, or PMOs, can
protect monkeys infected with Ebola
and Marburg viruses from going on to
develop lethal hemorrhagic fever,
which has a 90 per cent fatality rate in
humans. They are now proceeding
with clinical trials on primates.

Because clinical trials cannot be
conducted ethically in humans, the
FDA permits such drugs to be tested in
primates.  If the tests prove successful,
the drugs will then be tried when
outbreaks of infection occur in Africa.

US Army Medical Research Institute of
Infectious Diseases (USAMRIID) based
at Fort Detrick, Maryland, collaborated
with AVI BioPharma, a Washington-
based biotechnology firm.

There are currently no vaccines or
effective treatments for the Ebola and
Marburg filoviruses, which are
commonly transmitted through blood
and bodily fluids. However, infection
can also occur via the aerosol route,
which is why they are a cause of grave
concern as potential weapons in
biological warfare or terrorism.

Ebola and Marburg are both members
of the filovirus family, long threads of
RNA that infect humans and other
primates, causing hemorrhagic fever
and, almost inevitably, death. Although
researchers have been working
frantically to develop drugs to treat
infections, none has yet reached the
stage of clinical testing.

The novel antisense drugs are useful
against viral diseases because they
are designed to enter cells and
eliminate viruses by preventing their
replication. The drugs act by blocking
critical viral genetic sequences,
essentially giving the infected host time
to mount an immune response and
clear the virus.



AGENT PRX-105 AS ANTIDOTE FOR
NERVE GAS
Killing within minutes of exposure,
nerve gas is considered one of the
most toxic chemical agents known to
man. First developed in pre-World War
II Germany, nerve gas and nerve
agents are still considered a major
military threat to homeland security in
the United States. Now, a safeguard
may be at hand with PRX-105, a novel
compound being developed in Israel
that offers protection against both
nerve agents and the organic
phosphorous compounds used in the
pest control industry.

Protalix Biotherapeutics, the Israeli
company developing the new drug,
has just reported completion of the first
phase of clinical trials on humans with
PRX-105.

Nerve agents act through the skin,
lungs or eyes, where the phosphorus-
containing organic chemicals
(organophosphates) disrupt the
mechanism through which nerves
transfer messages to the body's
organs, causing asphyxiation as those
exposed lose control over their
respiratory muscles.
As part of the war against terror, the
US Department of Defense is now
working to find an antidote to nerve
agents, classified as a weapon of mass
destruction.

Developed through the genetic
engineering of carrot cells, PRX-105 is
an enzyme which is based on a
molecule licensed to Protalix by
Yissum, the technology transfer arm of
the Hebrew University of Jerusalem. It
was first developed by Prof. Hermona
Soreq.

And given the nature of the biodefense
indications under which Protalix is
developing the PRX-105, trials of PRX-
105 in humans (Phase II and Phase III)
will not be required.

Media sources report that Protalix's
anti-nerve gas drug could be ready as
early as next year, and that sales will
be contingent on a commitment on the
part of the US military to purchase a
drug that can counter chemical
weapons.


CELL PHONE TO DETECT HAZARDS
A tiny silicon chip that works a bit like a
nose may  detect dangerous airborne
chemicals and alert emergency
responders through the cell phone
network.

In collaboration with Rhevision, Inc., a
small startup company located in San
Diego, Sailor's research group at
UCSD has successfully finished the
first phase of development of the
sensor and have begun to work on a
prototype that will link to a cell phone.

The sensor, a porous flake of silicon,
changes color when it interacts with
specific chemicals. By manipulating the
shape of the pores, the researchers
can tune individual spots on the silicon
flake to respond to specific chemical
traits.

"It works a little like our nose,"  Dr
Sailor said. "We have a set of sensory
cells that detect specific chemical
properties. It's the pattern of activation
across the array of sensors that the
brain recognizes as a particular smell.
In the same way, the pattern of color
changes across the surface of the chip
will reveal the identity of the chemical."


VACCINE RIVAX AGAINST DEADLY
RICIN
Through its Biodefense Division,
Soligenix is developing biomedical
countermeasures pursuant to the
Project BioShield Act of 2004.
Soligenix's lead biodefense product in
development is a recombinant subunit
vaccine called RiVax, which is
designed to protect against the lethal
effects of exposure to ricin toxin. RiVax
has been shown to be well tolerated
and immunogenic in a Phase 1 clinical
trial in normal volunteers.




OVERVIEW OF OTHER PROJECTS

Following the terrorist attacks of 2001,
both the Administration and Congress
determined that the federal
government needed new medical
countermeasures (such as diagnostic
tests, drugs, vaccines, and other
treatments) to respond to an attack.


Representatives of the pharmaceutical
industry argued that, because these
diseases and conditions occur
infrequently, the private sector
perceived little economic incentive to
invest the millions of dollars required to
bring treatments to market.


In 2004, Congress passed the Project
BioShield Act to encourage the
development of medical
countermeasures. The 108th
Congress also appropriated $5.6
billion to acquire countermeasures for  
years 2004 to 2013.


Project BioShield Act of 2004 has
three main provisions. The first
provision provides expedited
procedures for terrorism-related
spending. The second provision
creates a government-market
guarantee by permitting the HHS
Secretary to obligate funds to
purchase countermeasures while they
still need several more years of
development. The third provision
authorizes the Secretary to temporarily
allow the emergency use of
countermeasures that lack FDA
approval.



The first Project BioShield contract was
announced on November 4, 2004.

The government contracted with
VaxGen, Inc., for delivery of 75 million
doses of a new type of anthrax vaccine
within three years. This contract had a
value of $879 million. In  2006  the
contract was terminated because
VaxGen, Inc., failed to meet a contract
milestone.

Subsequent contracts include:

• $691 million for 29 million doses of
the currently approved anthrax vaccine
(anthrax vaccine adsorbed or AVA)
from Emergent BioSolutions, Inc.;
• $334 million for 65,000 doses of
Raxibacumab (ABthrax), a treatment
for anthrax, from Human Genome
Sciences, Inc.;
• $144 million for 10,000 doses of
Anthrax Immune Globulin, a treatment
for anthrax, from Cangene Corporation;
• $505 million for 20 million doses of a
new smallpox vaccine (Modified
Vaccinia Ankara or MVA) from
Bavarian Nordic, Inc.;
• $433 million for 1.7 million doses of
ST-246, an antiviral treatment for
smallpox, from SIGA Technologies, Inc.;
• $414 million for 200,000 doses of
botulinum antitoxin, a treatment for
botulinum toxin exposure, from
Cangene Corporation;
• $18 million for 5 million doses of a
pediatric form of potassium iodide, a
treatment for radioactive iodine
exposure, from Fleming
Pharmaceuticals; and
• $22 million for 395,000 doses of
pentetate calcium trisodium (also
known as Ca- DTPA) and 80,000
doses of pentetate zinc trisodium (also
known as Zn-DTPA), two treatments
for internal radioactive particle
contamination, from Akorn, Inc.

Thus, excluding the canceled VaxGen
contract, HHS has obligated
approximately $2.56 billion to date.

Future targets for Project BioShield
procurement include countermeasures
against anthrax, smallpox, viral
hemorrhagic fevers, and radiation.