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Alan Franciscus
Editor-in-Chief
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In This Issue:
• Hepatitis
C Victims Fight for Secret Files
• Sirna
Therapeutics Demonstrates Systemic Efficacy of siRNAs in Multiple
Animal Models
• Genetic
Vaccine Promising against Chronic Hepatitis C
• Vertex
Pharmaceuticals Announces Initiation of First Human Clinical
Trial for VX-950, an Investigational Oral Protease Inhibitor
for the Treatment of Hepatitis C
• Isis Pharmaceuticals
(ISIS) Gains Full Ownership of Orasense(TM) and HepaSense(TM)
Subsidiaries and Eliminates Future Royalty Payments to Elan
Corporation PLC (ELN)
• Company
to Issue Worldwide Alert to Hospitals about Dialysis Machines
• Sidney
Pestka, M.D., Wins Sixteenth Annual Warren Alpert Foundation
Prize
June 6th, 2004
Hepatitis
C Victims Fight for Secret Files -Haemophiliacs in Court Move
Demand to See Official Papers
Liam McDougall, Health Correspondent
Source: Sunday Herald
HAEMOPHILIACS who contracted deadly liver
diseases from NHS blood products have demanded the release
of 600 classified documents which they believe show the government
is liable for their illnesses.
Campaigners infected with hepatitis C have
written to the Scottish and Westminster health ministers,
Malcolm Chisholm and John Reid, calling on them to open files
containing information on blood policy decisions taken by
the UK government between 1972 and 1986, during which time
thousands became ill.
The documents have been kept secret since
1990, when the government refused to reveal their contents
to patients who were suing after contracting HIV through the
NHS. According to court papers, judges who saw the documents
believed the govern ment had a case to answer but, at a time
when hundreds were dying from Aids, recommended that those
infected accept the government’s offer of compensation
rather than fight a lengthy court battle.
Since then, the documents – which
relate largely to matters of policy – have been kept
secret and given “public interest immunity”.
Now, the Manor House Group, formed by haemophiliacs
infected with hepatitis C, say the papers could reveal how
thousands of patients contracted the disease after having
blood transfusions and clotting treatments. They want a public
inquiry into how more than 5000 people were infected through
blood products from the 1970s to the 1990s. More than 1000
have died.
Peter Mossman, the group’s vice chairman,
has written to John Reid demanding the files are made public.
He stated: “Successive health ministers have always
said if any other information was forthcoming, they would
look into it. The Manor House Group believes not all the relevant
information is in the public domain.”
Last week, individual haemophiliacs also
wrote to Reid and Chisholm calling to have the files released
under incoming freedom of information legislation.
Bruce Norval, of Fortrose, near Inverness,
wrote to Chisholm, citing new freedom of information rules.
He said: “These documents are of direct relevance to
my case as a haemophiliac infected with viruses through contaminated
blood products given to me by the NHS. The scale of the disaster
inflicted on Scotland’s haemophiliacs was avoidable.”
Mike Kenwright, a haemophiliac from Cheshire
who contracted hepatitis C, said: “These 600 documents
lie hidden in the Department of Health. I would ask whether
they have been hidden because of what they would prove. I
believe these documents will show the government was negligent
in allowing thousands of us to become infected.”
According to court papers seen by the Sunday
Herald, the 600 documents contain a number of sensitive pieces
of information, including details of exchanges between ministers
and senior officials on how policy decisions were arrived
at.
Campaigners believe the dates which the
documents relate to are significant because at that time the
UK pool of donors of the Factor VIII clotting agent expanded
from around 200 to about 15,000, increasing the level of risk
to haemophiliacs.
Norval added: “ The government has
said it believes all information is in the public domain but
that it would consider any new evidence . Well, here is new
evidence.”
Opposition politicians also called on the
government to release the information.
The fresh calls to reveal the documents
come days after details of a government ex-gratia payment
scheme were announced. The Skipton Fund, which will give infected
haemophiliacs up to £45,000 each, is due to take claims
from next month. However, several haemophiliacs called the
fund only to be told that the application forms were not yet
ready.
Asked about Norval’s letter, an Executive
spokeswoman said: “The health minister’s office
has just received the letter. We will consider it and respond
in due course.”
A Department of Health spokesman said he
could not comment on any letters as they had not yet been
received.
He added: “The government does not
accept that any wrongful practices were employed and does
not consider a public inquiry justified, as it does not believe
any new light would be shed on this issue as a result.”
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June 7th, 2004
Sirna
Therapeutics Demonstrates Systemic Efficacy of siRNAs in Multiple
Animal Models
Source: PRNewswire
BOULDER, Colo.-- Sirna Therapeutics, Inc.
(NASDAQ:RNAI) today announced in a presentation at the BIO
2004 Annual International Convention that it has demonstrated
reproducible and robust preclinical systemic efficacy using
its proprietary chemically modified and formulated short interfering
RNAs (siRNAs). Nassim Usman, Ph.D., Sirna's Senior Vice President
and Chief Operating Officer, presented the Company's preclinical
results during today's morning panel discussion, "RNAi:
The New Frontier in Gene Silencing."
Dr. Usman reported, "About a year
and a half ago, Science Magazine named RNAi, or RNA interference,
as the leading scientific 'Breakthrough of the Year.' Sirna
has overcome major hurdles to transform this breakthrough
science into a clinical-stage compound and to establish a
robust portfolio of preclinical leads. The Company and its
collaborators have demonstrated systemic efficacy in several
different animal models of disease, using routes of administration
that are appropriate for a human therapeutic."
Using normal systemic delivery Sirna researchers
have achieved a reproducible one-log reduction of hepatitis
B (HBV) viral DNA and S-antigen in a preclinical animal model
using Sirna's proprietary modified siRNAs. The Company is
using HBV as a surrogate model of hepatitis C (HCV) infection.
Based on these groundbreaking results the Company expects
to select an HCV clinical candidate by the end of this year.
As a further demonstration of the remarkable
power of the RNAi mechanism and Sirna's proprietary modified
siRNAs, the Company has developed siRNAs that provide long-term
duration of effect in an animal model. Sirna researchers,
in collaboration with Dr. Beverly Davidson, Professor at the
University of Iowa, have achieved a 75 - 95% knockdown of
a target gene (Green Fluorescent Protein) in the livers of
transgenic animals for periods up to 3 weeks following a single,
normal intravenous injection.
In addition to the Company's work on systemic
efficacy, Sirna has successfully demonstrated efficacy in
three different animal models of ocular angiogenesis including
choroidal neovascularization (CNV) using two different routes
of local administration. Following a pre-IND meeting with
the FDA in March of this year, the Company is on schedule
to file its IND in the fourth quarter of this year for Sirna-027,
a chemically modified siRNA targeting VEGF Receptor-1. The
Company is completing toxicology and manufacturing of clinical
trial material for Sirna-027, and is finalizing the Phase
I clinical protocol in collaboration with three investigators.
Sirna Therapeutics further announced that
Howard Robin, Sirna's President and Chief Executive Officer,
will present information on the Company's progress in a corporate
presentation on Tuesday, June 8th at 10:45 AM Pacific Time
during the BIO 2004 conference.
About Sirna Therapeutics
Sirna Therapeutics is using its proprietary technology and
expertise in nucleic acids to develop a new class of nucleic
acid-based therapeutics involving RNA interference. RNAi is
a mechanism used by cells to regulate the expression of genes
and replication of viruses. The RNA interference mechanism
uses short interfering RNA (siRNA) to induce the destruction
of target RNA using naturally occurring cellular protein machinery.
Harnessing the natural phenomenon of RNAi holds potential
for the development of a new class of drugs with specificity
towards a wide range of diseases that result from undesirable
protein production or viral replication. More information
on Sirna Therapeutics is available on the company's web site
at www.sirna.com.
Statements in this press release which
are not strictly historical are "forward-looking"
statements which should be considered as subject to many risks
and uncertainties, including early stage of development and
short operating history, ability to achieve and maintain profitability,
ability to obtain and protect patents, risk of third-party
patent infringement claims, ability to engage collaborators,
ability to obtain regulatory approval for products, concentration
of stock ownership, and availability of materials for product
manufacturing. These and additional risk factors are identified
in the Company's Securities and Exchange Commission filings,
including the Forms 10-K and 10-Q and in other SEC filings.
Sirna undertakes no obligation to revise or update any forward-looking
statements in order to reflect events or circumstances that
may arise after the date of this release.
For further information, please contact
Howard W. Robin, President & CEO of Sirna Therapeutics,
Inc., +1-303-449-6500; or Investors, E. Blair Schoeb, or Media,
Justin Jackson, both of Burns McClellan, Inc., +1-212-213-0006,
for Sirna Therapeutics, Inc.
Source: Sirna Therapeutics, Inc.
CONTACT: Howard W. Robin, President & CEO of Sirna Therapeutics,
Inc.,
+1-303-449-6500; or Investors, E. Blair Schoeb, or Media,
Justin Jackson, both
of Burns McClellan, Inc., +1-212-213-0006, for Sirna Therapeutics,
Inc.
Web site: http://www.sirna.com/
Back to top
Genetic
Vaccine Promising Against Chronic Hepatitis C
Source: Karolinska Institutet
A potential vaccine candidate against chronic
hepatitis C (HCV) infections is presented in a thesis from
Karolinska Institutet. The new genetic vaccine can activate
immune responses that are needed to clear HCV, a disease that
today is difficult to treat effectively.
The hepatitis C virus (HCV) is a major cause of chronic liver
disease worldwide. It is estimated that HCV affects approximately
170 million people around the world. Today, no vaccine is
available to prevent or cure HCV infections. Antiviral therapy
is used quite effectively, but in 60-80 per cent of the patients
become chronic carriers of the virus in their liver. One feature
of HCV infection is the high rate of viral persistence. The
mechanism of viral persistence is largely unknown, although
the high genetic variability is thought to play a key role.
In Lars Frelin’s thesis the HCV NS3 protein is studied
in detail since it performs key functions in the viral life
cycle. These are unwinding and strand separation of the viral
RNA and proteolytic processing of the precursor polyprotein.
To obtain the complete protease the NS4A co-factor was included
in the NS3-based vaccines. NS4A has been shown to enhance
the stability of NS3 and to target the NS3/4A complex to intracellular
membranes. The latter is most likely of importance for the
formation of the replication complex. Also, the NS3 region
has a limited genetic variability and several studies have
now demonstrated that NS3-specific CD4+ and CD8+ T-cell responses
are crucial for the resolution of HCV infections. Thus, several
factors suggest that the NS3 region should be well suited
for vaccine development.
The results show that HCV NS3-based genetic
vaccines effectively primed both humoral and cellular immune
responses in mice. NS3/4A was shown to prime a Th1 CD4+ T-cell
response. The inclusion of NS4A in NS3-based vaccines primed
antibody, CD4+, and CD8+ T-cell responses that were superior
to those primed by NS3-gene alone. Thus, NS4A enhanced the
immunogenicity of NS3. The studies also show that enhancement
of the immunogenicity was most probably a result of the higher
expression levels of NS3 generated by the inclusion of NS4A.
Further results show that the overall immunogenicity of NS3/4A
could be further enhanced by codon optimization or by mRNA
amplification using the Semliki forest virus (SFV) replicon.
The NS3 protein expression levels were further improved by
either codon optimization and mRNA amplification. Subsequently,
both these modifications enhanced the NS3-specific immune
responses. One concern in development of genetic vaccines
is that the gene displays unwanted properties when expressed
in vivo. Therefore, a new transgenic mouse expressing the
HCV NS3/4Aprotein in the liver was generated. The protein
expression was restricted to the liver to mimic the in vivo
situation during a HCV infection. Protein expression was localized
to the cytoplasm of the hepatocytes and displayed a similar
staining pattern as seen in hepatocytes from HCV infected
individuals. The intrahepatic protein expression did not cause
overt liver damage, except for a slight enlargement of the
liver. However, the NS3/4A-transgenic mice displayed less
spontaneously appearing intrahepatic inflammatory foci, which
are commonly found in laboratory mice. Thus, expression of
NS3/4A-protein may affect the distribution of immune cells
within the liver.
The present studies demonstrate that NS3/4A-based
genetic vaccines effectively prime humoral and cellular immune
responses. Intra-hepatic expression of NS3/4A did not cause
any spontaneous liver disease or overt pathology suggesting
that it safely can be used in genetic vaccines. Thus, the
NS3/4A gene can safely activate immune responses that are
similar to those found in humans who can clear HCV. The NS3/4A
should therefore be a potential vaccine candidate against
chronic HCV infections.
Thesis: Development
of vaccines and experimental models for chronic infections
caused by the hepatitis C virus
Author: Lars
Frelin, Department of laboratory medicine, Karolinska Institutet,
Stockholm. Sweden.
Contact: Lars Frelin, phone +46 8 585 879
33, +46 70 424 3001 or mail lars.frelin@labmed.ki.se
or Professor Matti Sällberg, phone +46 8 524 838 03,
+46 8 585 879 39 or mail matti.sallberg@labmed.ki.se
Back to top
June 8th, 2004
Vertex
Pharmaceuticals Announces Initiation of First Human Clinical
Trial for VX-950, an Investigational Oral Protease Inhibitor
for the Treatment of Hepatitis C
Source: PRNewswire
CAMBRIDGE, Mass-- Vertex Pharmaceuticals
Incorporated (NASDAQ:VRTX) announced today the initiation
of a Phase I clinical trial for VX-950, an investigational
oral protease inhibitor for the treatment of hepatitis C virus
(HCV) infection. The objective of this trial is to assess
safety, tolerability and pharmacokinetics in escalating single
doses of VX-950 in healthy volunteers. Approximately 35 healthy
subjects will participate in the study, which is being conducted
in Europe. Successful completion of the Phase I clinical trial
will enable a first study of VX-950 in HCV-infected patients.
Such a study is currently planned to start in the fourth quarter
of 2004.
VX-950 is Vertex's lead oral HCV protease
inhibitor and one of a new class of direct antivirals in development
for the treatment of HCV. Preclinical studies have shown that
VX-950 significantly reduces levels of HCV RNA in both an
in vitro replicon system and infectious virus assays. At a
scientific conference in October 2003, Vertex scientists reported
that VX-950 reduced HCV RNA 10,000-fold (4 log 10) in nine
days in an in vitro replicon assay. Preclinical pharmacokinetic
studies have indicated that VX-950 is orally bioavailable
and achieves excellent exposure in the liver, the target organ
for HCV treatment. The initiation of clinical testing of VX-950
represents a first step towards establishing the safety and
tolerability in humans.
"Preclinical data to date have indicated
that direct antivirals such as VX-950 may represent a powerful
new approach to the treatment of HCV infection," stated
John J. Alam, M.D., Senior Vice President of Drug Evaluation
and Approval at Vertex. "Initiation of human clinical
trials for VX-950 reflects Vertex's commitment to leadership
in the development and commercialization of novel antivirals
for the treatment of HCV infection, and it is one of several
important clinical milestones for Vertex's proprietary development
programs in 2004."
Clinical Need and Market Opportunity
in HCV Infection
Chronic hepatitis C virus (HCV) infection is a serious public
health concern affecting approximately 2.7 million people
in the United States. HCV causes inflammation of the liver,
which may lead to fibrosis and cirrhosis, liver cancer, and
ultimately, liver failure. Cirrhosis of the liver resulting
from chronic HCV infection is the leading indication for liver
transplantation in the U.S. Due to the asymptomatic nature
of HCV infection, it often goes undetected for up to 20 years
following initial infection. Worldwide, the disease strikes
as many as 185 million people. Each year, 8,000 to 10,000
people in the U.S. die from complications of HCV.
The current standard of care in HCV treatment
is a combination of weekly injections of pegylated interferon
alpha (peg-IFN) and daily oral dosing of ribavirin. This combination
therapy provides a sustained viral response for only 40 to
50 percent of patients chronically infected with genotype
1 HCV, the most difficult viral strain to treat and the most
common form in the U.S.
Vertex's drug development portfolio includes
two different approaches for advancing the future standard-of-care
in HCV. In addition to VX-950, Vertex is developing merimepodib,
an IMPDH inhibitor in combination with pegylated interferon
alpha (peg-IFN) and ribavirin. Addition of merimepodib to
standard therapy has the potential to enhance antiviral activity
and improve clinical outcomes for a larger percentage of patients.
Vertex owns worldwide development and commercialization rights
for both merimepodib and VX-950.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology
company committed to the discovery and development of breakthrough
small molecule drugs for serious diseases. The Company's strategy
is to commercialize its products both independently and in
collaboration with major pharmaceutical partners. Vertex's
product pipeline is principally focused on viral diseases,
inflammation, autoimmune diseases and cancer. Vertex co-promotes
the new HIV protease inhibitor, Lexiva(TM), with GlaxoSmithKline.
This press release may contain forward-looking
statements, including statements that (i) successful completion
of the Phase I trial would enable a first study to assess
dosing in patients in the fourth quarter of 2004; (ii) preclinical
testing results suggest that VX-950 may represent a powerful
new approach in the treatment of HCV infection; and (iii)
addition of merimepodib in combination therapy has the potential
to improve clinical outcomes. While management makes its best
efforts to be accurate in making forward-looking statements,
such statements are subject to risks and uncertainties that
could cause Vertex's actual results to vary materially. These
risks and uncertainties include, among other things, the risks
that clinical trials for merimepodib or VX-950 may not proceed
as planned due to technical, scientific, supply or patient
enrollment issues, that actual clinical studies of VX-950
will not reflect the results obtained in nonclinical testing,
that clinical results may not demonstrate the value of combination
therapies for HCV patients generally, and further clinical
testing of merimepodib will not confirm its potential as an
enhancement to combination therapy, and other risks listed
under Risk Factors in Vertex's form 10-K filed with the Securities
and Exchange Commission on March 15, 2004.
Lexiva(TM) is a registered trademark of
the GlaxoSmithKline group of companies.
Vertex's press releases are available at www.vrtx.com.
Vertex Contacts:
Lynne H. Brum, VP, Corporate Communications and Financial
Planning (617) 444-6614
Michael Partridge, Director, Corporate Communications (617)
444-6108
Lora Pike, Manager, Investor Relations (617) 444-6755
Source: Vertex Pharmaceuticals Incorporated
CONTACT: Lynne H. Brum, VP, Corporate Communications
and Financial
Planning, +1-617-444-6614, or Michael Partridge, Director,
Corporate
Communications, +1-617- 444-6108, or Lora Pike, Manager, Investor
Relations,
+1-617-444-6755, all of Vertex Pharmaceuticals Incorporated
Web site: http://www.vrtx.com/
Back to top
June 9th, 2004
Isis
Pharmaceuticals (ISIS) Gains Full Ownership Of Orasense(TM)
And HepaSense(TM) Subsidiaries And Eliminates Future Royalty
Payments To Elan Corporation PLC (ELN)
Source: PRNewswire
CARLSBAD, Calif., -- Isis Pharmaceuticals,
Inc. announced today that it has entered into an agreement
with a subsidiary of Elan Corporation, plc, to acquire Elan's
minority interest in Orasense and HepaSense, joint ventures
arising out of prior collaborations between Isis and Elan.
Through this acquisition, Isis has eliminated all future royalties
to Elan related to the oral delivery platform developed within
the Orasense collaboration and to ISIS 14803, Isis' antisense
drug for the treatment of the hepatitis C virus, which is
currently in Phase 2 clinical trials and was the focus of
the HepaSense collaboration. As previously announced, Elan's
participation in these collaborations concluded in January
2003 and November 2002, respectively.
In addition to eliminating all future royalty
payments to Elan, the agreement allows Elan to transfer its
shares of Isis Series B Preferred Stock to a third party.
Upon transfer, the preferred stock will immediately convert
to 1,055,502 shares of Isis common stock, eliminating the
5 percent in-kind dividend, thereby reducing future dilution
of approximately 86,000 shares of Isis' common stock. Further,
Elan has agreed to surrender its warrant to purchase 14,881
shares of Isis common stock to Isis for cancellation.
"We are extremely pleased to have
completed this transaction as it allows us to recognize the
full financial potential of our oral delivery platform and
our proprietary drug to treat hepatitis C. In addition, it
simplifies our capital structure and eliminates dividend accretion
of approximately $1.2 million between now and maturity in
2006 as a result of the early conversion of the Series B Preferred
Stock," said B. Lynne Parshall, J.D., Executive Vice
President and Chief Financial Officer of Isis. "This
is the latest achievement in our ongoing efforts to further
strengthen our financial position and streamline our balance
sheet. As a result of these efforts over the past two years,
we have retired more than $125 million in high interest debt,
eliminated a significant amount in future interest payments
and reduced total potential dilution of our common stock by
2.2 million shares."
Isis Pharmaceuticals, Inc. is exploiting
its expertise in RNA to discover and develop novel human therapeutic
drugs for its pipeline and for its partners. The company has
successfully commercialized the world's first antisense drug
and has 11 antisense products in development to treat metabolic,
cardiovascular, inflammatory and viral diseases and cancer.
Through its Ibis Therapeutics(R) program, Isis is developing
a biosensor to identify infectious organisms, and discovering
small molecule drugs that bind to RNA. As an innovator in
RNA-based drug discovery and development, Isis is the owner
or exclusive licensee of more than 1,300 issued patents worldwide.
Additional information about Isis is available at http://www.isispharm.com/.
This press release includes forward-looking
statements regarding our business, our financial position,
the therapeutic and commercial potential of our technologies
and products in development and the benefit we expect to receive
from the transaction described herein. Any statement describing
our goals, expectations, intentions or beliefs is a forward-looking
statement and should be considered an at-risk statement, including
those statements that are described as Isis' clinical goals.
Such statements are subject to certain risks and uncertainties,
particularly those inherent in the process of developing technology
and systems used to identify infectious agents, in discovering
and commercializing drugs that are safe and effective for
use as human therapeutics, and in the endeavor of building
a business around such products and services. Actual results
could differ materially from those discussed in this press
release. As a result, you are cautioned not to rely on these
forward-looking statements. These and other risks concerning
Isis' research and development programs are described in additional
detail in Isis' Annual Report on Form 10-K for the year ended
December 31, 2003, and quarterly report on Form 10-Q for the
quarter ended March 31, 2004, which are on file with the U.S.
Securities and Exchange Commission. Copies of these and other
documents are available from the company.
Ibis Therapeutics(R) is a registered trademark
of Isis Pharmaceuticals, Inc.
Orasense(TM) and HepaSense(TM) are trademarks of Isis Pharmaceuticals,
Inc.
Isis Pharmaceuticals Inc.
CONTACT: Kristina Peterson of Isis Pharmaceuticals Inc.,+1-760-603-2521
Web site: http://www.isispharm.com/
Back to top
June 10th, 2004
Company
to Issue Worldwide Alert to Hospitals About Dialysis Machines
Canadian Press
Chicago-based Baxter International is today
expected to issue a global alert to hospitals using its hemodialysis
machines - a response to concerns raised in British Columbia
that the equipment may pose the risk of contamination between
patients. Hundreds of British Columbia dialysis patients are
being contacted regarding the small chance they have been
put at risk of contracting a blood-borne illness like HIV
or hepatitis B or C; some will have to take blood tests. The
warning came after the discovery of blood inside tubing where
it should not have been in a Baxter Aurora machine at Royal
Jubilee Hospital in Victoria late last month.
Baxter spokesperson Cindy Resman said the
company has "a huge team working on this" and will
contact its customers around the world to ensure they are
following the procedures in its manuals.
Michele Stewart, spokesperson for the provincial
government, said Health Canada inspectors are interviewing
company officials and will send a letter to all Canadian hospitals
about the matter. Dr. Andeera Levin, medical director of the
provincial renal agency, said there have been no cases of
British Columbia dialysis patients contracting hepatitis in
the past year. The patients are tested monthly for hepatitis
B and about every six months for hepatitis C. While some dialysis
patients have HIV and more have hepatitis, these patients
do not use the same machines as uninfected patients.
The British Columbia Nurses' Union raised a red flag about
Baxter last year because of lawsuits from deaths in Europe
linked to Baxter products, union official Peggy Eburne said
Thursday. Baxter spokesperson Deborah Spak said those problems
related to faulty dialysers or filters and have nothing to
do with the current machines. Baxter stopped making the faulty
filters, closed the manufacturing facilities and settled with
the families that sued, she said.
Back to top
Sidney
Pestka, M.D., Wins Sixteenth Annual Warren Alpert Foundation
Prize
Source: PRNewswire
PISCATAWAY, N.J.-- Sidney Pestka, M.D.,
whose pioneering research made interferon therapy for hepatitis
C and other viral diseases a reality, was named yesterday
with two others as winner of the sixteenth annual Warren Alpert
Foundation Scientific Prize.
The Foundation recognizes Dr. Pestka, Chairman
and Chief Scientific Officer of PBL Biomedical Laboratories,
for his seminal accomplishments in purifying, characterizing
and cloning human interferon-alpha, or Hu-IFN-alpha, a virus-fighting
substance produced by white blood cells. David V. Goeddel,
Ph.D., founder and Chief Executive Officer of Tularik, Inc.,
and Charles Weissmann, M.D., Ph.D., the Institute of Neurology,
University College London and Director of the Department of
Infectology, Scripps Florida Research Institute, share the
prize for crucial work in which they cloned Hu-IFN-alpha in
the bacterium E. coli and demonstrated that biologically active
interferon could be produced in large enough quantities to
make it a practical treatment for disease. The Foundation
will divide among the winners a $150,000 award.
Interferon-alpha is the key component of
the only known treatment regimen for hepatitis C, a viral
disease of the liver spread by exposure to the blood of those
already infected. Approximately 170 million persons suffer
from chronic hepatitis C infection worldwide, and two to three
million new cases are diagnosed each year. If untreated, chronic
hepatitis C can lead to cirrhosis, and infection raises the
risk of liver cancer 100-fold. But using a combined regimen
of pegylated interferon-alpha and ribavirin, doctors now cure
about 50 to 80 percent (depending on the viral strain) of
chronically infected hepatitis patients, heading off permanent
liver damage and cancer.
Interferon-alpha is used to treat several
other viral diseases, including hepatitis B and human papillomavirus,
or HPV, the most common sexually transmitted disease in the
United States and the cause of most cervical cancer. Interferon
is also used in the treatment of cancer. It has been shown
to be effective in various forms of leukemia and in Kaposi's
sarcoma, a cancer associated with HIV infection.
Scientists had noticed during the 1930s
that viruses tend to strike one at a time. It is quite rare,
for example, for a child to have measles and chickenpox simultaneously.
Researchers explained this phenomenon by way of a theory of
"viral interference," which proposed that cells
exposed to a virus release some agent that protects the body
from infection by other viruses. In 1957, scientists in London
discovered a highly potent protein that played just such a
protective role after viral infection, and they accordingly
named it interferon.
The discovery of interferon, a natural
cell product that acts against a wide range of viruses by
protecting cells from infection and stimulating the immune
system, was greeted with great excitement, and its clinical
future seemed bright. However, cells produce interferon in
miniscule amounts, and two decades' worth of attempts to purify
and characterize the protein met with repeated failure.
Pestka first found he could greatly increase
the interferon yield in his experiments by using white blood
cells from leukemia patients, and then, after developing a
new technique-reverse-phase high-performance liquid chromatography,
now used in biological laboratories throughout the world-he
successfully purified ten unique interferon-alpha proteins
in 1978.
Pestka's later collaborative work with
Weissman (then at the University of Zurich) and Goeddel (then
at Genentech) then led to the production, in bacteria, of
as much human interferon-alpha per liter as could be made
from the white blood cells of 100 donors. Moreover, the protein
created in these experiments was potent enough to protect
monkeys from otherwise deadly viral infections.
The translation of this research from the
laboratory to the clinic was remarkably rapid. Recombinant
interferon-alpha was first injected into a human patient in
1981, and the drug received FDA approval for the treatment
of leukemia just five years later. Today, millions of patients
throughout the world have received interferon-alpha for many
conditions that were previously untreatable, and other potential
uses for interferon continue to be explored in clinical trials
and in basic research.
The Warren Alpert Foundation Scientific
Prize
The Warren Alpert Foundation Scientific Prize is given each
year for far- reaching scientific breakthroughs that have
had a direct impact on the treatment of disease. Each year
the Foundation receives 30 to 50 nominations for the Alpert
Prize from scientific leaders worldwide. Prize recipients
are selected by the Foundation's scientific advisory board,
made up of internationally recognized biomedical scientists.
See http://www.hms.harvard.edu/fa/AlpertPrize/
for more information.
PBL Therapeutics
PBL Therapeutics is producing the next generation of interferon
molecules -- Ultra Interferons(TM), which can be 20 to 30
times more potent than the interferons currently used in therapy.
Equally significant, PBL Therapeutics has also developed its
Sustained Release Protein Delivery (SuRe-PD(TM)) technology
to deliver interferon directly to tumors and release the drug
slowly over time. Together, Ultra Interferons(TM) and SuRe-PD(TM)
are expected to enable PBL to develop more effective cancer
treatments, with dramatically reduced side effects.
PBL Therapeutics, an emerging biotechnology
company, has developed three technology platforms: (1) Using
its drug discovery platform, PBL can identify a virtually
unlimited number of interferon variants that are produced
naturally in cancer cells. Selected variants under development
are 20 to 30 times more effective than Alpha 2 interferon,
the first and only interferon approved for cancer therapy.
The Company screens these molecules to determine which "Ultra
Interferon(TM)" possesses the preferred characteristics
to treat the diseases of choice. (2) PBL then formulates the
Ultra Interferon. using its Sustained Release Protein Delivery
("SuRe-PD(TM)") technology to deliver the interferon
locally, and release it slowly over time. Together, these
two technology platforms enable PBL Therapeutics to develop
the most promising interferon molecule, and to maximize the
effectiveness of this molecule through extended-release, localized
delivery. (3) PBL Therapeutics' phosphorylation technology,
used primarily to radiolabel monoclonal antibodies (MAbs),
significantly improves upon the chemical labeling procedures
currently used to target radiation to tumors. MAbs with genetically
engineered phosphorylation sites facilitate the delivery of
high-energy radioactivity to cancer cells. Phosphorylated
MAbs retain higher activity and selectivity for tumor antigens
and appear less immunogenic than MAbs radiolabeled through
conventional chemical conjugation methods. This technology
complements the company's Ultra Interferons(TM), which stimulate
expression of the tumor cell surface antigens that phosphorylated
MAbs target.
Certain statements contained herein, including
statements regarding development of the Company's products,
services, markets, and future demands for the Company's products
and services, and other statements regarding matters that
are not historical facts, are forward-looking statements.
Such forward-looking statements include risks and uncertainties;
consequently, actual results may differ materially from those
expressed or implied thereby.
Contact:
Robert Pestka, President & CEO, PBL Therapeutics, +1 (732)
777-9123
PBL Therapeutics
CONTACT: Robert Pestka, President & CEO of PBL Therapeutics,
+1-732-777-9123
Web site: http://www.pblbio.com/
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