Back to News Review

HCV ADVOCATE WEEKLY NEWS REVIEW: A Review of HCV, HBV and HIV/HCV Coinfection Related News and Highlights

Week Ending: March 27^th, 2004

Alan Franciscus
Editor-in-Chief

In This Issue:

•Maxim Pharmaceuticals Completes Phase 1 Pharmacokinetic Trial of Orally Dosed Histamine
•De Novo Internal Neoplasms After Liver Transplantation
• Ribozyme Package Effective Against Hepatitis B Virus
•Enzo Biochem (ENZ) Reports On Preclinical Study That Points To Development Of New Compound For Treating Immune Mediated Diseases
•Nautilus Biotech Announces Progress On Belerofon, An Improved IFN Alpha With Single Amino Acid Sequence Change, Designed To Reduce Frequency Of Injection For Hepatitis C Chronic Infection And Cancer
•Homeless Advocate Concerned About Hospital's Suspect Lab Results
•Vencor to Begin E-commerce Distribution of FDA Approved at-Home Hepatitis C, Instant Cholesterol, Allergen and HIV Tests
•CombiMatrix and IrsiCaixa Expand HIV RNAi Collaboration to Include Hepatitis C
•Canadian Hepatitis C Network - Federal Budget Reaction
•Funds Cut for Hep C Treatment in Prisons
•Innogenetics-Improved Fibrosis in Hep C Vaccine
•Hepatitis B-Related Hepatocellular Carcinoma
•Health officer endorses safe drug site for Victoria




March 23rd, 2004

Maxim Pharmaceuticals Completes Phase 1 Pharmacokinetic Trial of Orally Dosed Histamine

The clinical trial evaluated the Company's oral formulation to establish the absorption, pharmacokinetics and maximum tolerated dose in healthy volunteers. In the trial, twenty-three volunteers were administered escalating doses of HD-O.

"This confirmation of absorption profile and tolerability of HD-O, in its first human clinical trial, provides the basis for advancing our clinical studies in chronic liver disease with an oral formulation," commented Larry Stambaugh, Maxim's Chief Executive Officer. "The availability of an oral formulation of histamine for liver disease patients is an important factor in making the treatment more convenient for patients that may need to take the therapy chronically. This enhances the commercial potential of histamine therapy."

Chronic liver diseases, including hepatitis, ALD and NASH, affect an estimated 25 million people in the U.S., approximately one in every ten. Hepatitis C is the leading blood-borne infection in the United States. The U.S. Center for Disease Control and Prevention estimates that over 4.5 million Americans are infected with the hepatitis C virus. The World Health Organization and other sources estimate that at least 200 million people are infected worldwide. Some experts estimate that without substantial improvements in treatment, deaths from hepatitis C will surpass those from HIV. Hepatitis C is the leading cause of liver cancer and the primary reason for liver transplantation in many countries. Even with recent advances, approximately half of patients still do not attain a sustained response with current therapies. NASH, non-alcoholic steatohepatitis, also called `fatty liver', is an inflammation of the liver associated with an increase of fat deposits in liver cells that may lead to severe liver damage and cirrhosis. NASH may occur in middle-aged, overweight, and often in diabetic patients who do not drink alcohol. ALD, caused by alcohol abuse, is one of the ten leading causes of death in the United States.

Overview of Histamine Therapy
Research has shown that oxygen free radicals released by certain immune cells can suppress the immune system and damage normal tissue, a process commonly referred to as oxidative stress. Oxidative stress, implicated in numerous diseases, is most pronounced in the liver and can damage or destroy liver tissue in patients with hepatitis and other chronic liver diseases. Histamine has been shown in preclinical testing to prevent the production and release of oxygen free radicals, thereby reducing oxidative stress. Accordingly, treatment with histamine has the potential to prevent or reverse damage induced by oxidative stress, thereby protecting critical cells and tissues, including the liver. Preclinical research, including results presented in 2003 at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) and published in the Journal of Inflammation (vol. 27 (5), p317-327), suggest that histamine can protect and promote the healing of the liver in models of ALD, NASH and partial surgical resection.

Research regarding histamine dihydrochloride has been the subject of more than 80 presentations at major scientific and clinical meetings, and has been published in more than 300 scientific and clinical articles. Ceplene(TM), Maxim's injectible form of histamine, has been tested in more than 17 trials in 2,000 patients, including hepatitis C patients. Maxim anticipates that any additional clinical testing of histamine for the treatment of chronic liver diseases will be with an oral formulation as in the completed Phase 1A trial announced today. A three-minute animation of the histamine mechanism of action in its injectible formulation as Ceplene(TM) can be viewed on the Company's website at www.maxim.com.

Maxim Overview
Maxim Pharmaceuticals is a global biopharmaceutical company with a diverse pipeline of therapeutic candidates for life-threatening cancers and liver diseases. Maxim's research and development programs are designed to offer hope to patients by developing safe and effective therapeutic candidates that have the potential to extend survival while maintaining quality of life.

Maxim's lead drug candidate Ceplene (subcutaneously delivered histamine dihydrochloride) is designed to prevent or inhibit oxidative stress, thereby reversing immune suppression and protecting critical immune cells. In November 2003, Maxim filed an application for market authorization in Europe for approval to market Ceplene for the treatment of advanced malignant melanoma. Ceplene is currently being tested in Phase 3 cancer clinical trials for advanced malignant melanoma with liver metastasis and acute myeloid leukemia. Phase 2 trials of Ceplene are also underway for the treatment of hepatitis C and advanced renal cell

In addition to Ceplene and oral-formulation histamine, Maxim is developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, which may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. Ceplene, the oral histamine formulation and the apoptosis inducers are investigational drugs and have not been approved by the U.S. Food and Drug Administration (FDA) or any international regulatory agency.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy, safety and intended utilization of Ceplene, the oral histamine formulation and the apoptosis inducers, and the conduct, results and timelines associated with the Company's clinical trials. Such statements are only predictions and the Company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in larger-scale clinical trials and the risk that the Company will not obtain approval to market its products. These factors and others are more fully discussed in the Company's periodic reports and other filings with the Securities and Exchange Commission.

Note: The Maxim logo is a trademark of the Company.

Editor's Note: This release is also available on the Internet at http://www.maxim.com.

CONTACT: Maxim Pharmaceuticals
Larry G. Stambaugh/Anthony E. Altig, 858-453-4040
or
Burns McClellan (Investors)
Aline Schimmel, 212-213-0006
or
CCG Investor Relations (Media)
Sean Collins/Valerie Bent, 818-789-0100

Back to top


De Novo Internal Neoplasms After Liver Transplantation
Source: www.gastrohep.com

Risk factors for de novo tumor development after liver transplantation include alcohol, HCV and possibly strong immunosuppression, find physicians in the latest issue of the American Journal of Transplantation.

In this study, physicians from Mexico and Spain determined the incidence and variables associated with post-liver transplantation (LT) de novo internal neoplasms development. They excluded skin tumors and hepatocellular carcinoma.

The team reviewed medical records for recipient/donor demographics, viral serology, cause of liver disease, interval from LT to tumor diagnosis, predisposing factors, immunosuppression and survival.

They found that 41 neoplasms developed in 772 recipients (5%) transplanted between 1991 and 2001.Hematologic neoplasms appeared earlier than solid neoplasms. American Journal of Transplantation

The time to tumor diagnosis was longer in patients transplanted before 1995 than in those transplanted afterwards (58 versus 22 months).

The physicians found that hematologic neoplasms (HN) appeared earlier than solid neoplasms (2 versus 21 months). HN were more prevalent in patients transplanted after 1995, they were associated with lower survival than solid neoplasms.

The team determined that HCV was the most frequent indication in HN (70%), and alcohol was the most frequent indication in solid tumors (71%).

Overall, risk factors for de novo neoplasms included alcohol and immunosuppression.

Dr Salvador Benllocha's team concluded, "In patients undergoing LT in recent years, there is a higher incidence of HN with de novo internal neoplasms developing at earlier time-points than in those transplanted years ago".

"Risk factors for tumor development include alcohol, HCV and possibly strong immunosuppression".

Am J Transplant 2004; 4(4): 596-604


Back to top



Ribozyme Package Effective Against Hepatitis B Virus
Source: Science Daily

HERSHEY, PA -- Penn State College of Medicine researchers have developed a tiny package that searches for and destroys up to 80 percent of hepatitis B virus in the livers of mice.

"This marks one of the few successful in vivo, or in-animal, models of an effective therapy to reduce the production of hepatitis B virus," said Gary Clawson, M.D., Ph.D., professor of pathology, biochemistry and molecular biology, Penn State College of Medicine. "Although this work focused on hepatitis B virus, our method of targeting and packaging ribozymes should also be applicable to the development of therapies to fight other viruses."

The study was published March 5 in the online version of the journal, Molecular Therapy, the official journal of the American Society of Gene Therapy, and will appear in the journal's April print edition.

Hepatitis B virus (HBV) attacks the liver and can cause lifelong infection, liver cancer and, eventually, death. Although HBV is treated with drugs, it cannot be cured. The chronic disease affects about 1.25 million Americans, 20 percent to 30 percent of whom acquired the virus in childhood. HBV is transmitted via blood or sexual activity, but also may be transmitted from mother to child during childbirth. Once infected, the virus continues to reproduce in the liver.

Clawson, who is also director of the Jake Gittlen Cancer Research Center at Penn State Milton S. Hershey Medical Center, and his team developed the SNIPAA cassette, which contains a double-dose of a special type of ribozyme called a trans-acting hammerhead ribozyme. Ribozymes are ribonucleic acid (RNA) segments that, like enzymes, cause chemical changes or splitting in other RNA segments. RNA, which is critical to the replication of DNA - life's instruction book - also is critical to the replication of viruses. The SNIPAA cassette was packaged in liposomes, typical vehicles for delivering drugs in the body, and the liposomes in turn were modified with proteins so that they would seek out the liver cells where the HBVs replicate.

Once at the liver cell, the SNIPAA cassette package is released into the cell and finds its way to the cell nucleus, where the active ribozymes are produced. The ribozymes destroy the viral RNA's ability to produce proteins by cleaving, or cutting, the viral RNAs, rendering them useless. Proteins are critical to virus replication.

First, Clawson and co-workers used proprietary in vitro selection techniques to identify the best target sites in HBV RNA, and then used cells in culture to test the effectiveness of the cassette. In the cell cultures, he found that the SNIPAA cassette containing a double-dose of ribozymes eliminated more of the virus over a period of three to five days than did cassettes containing a single dose of the ribozymes.

Specialized transgenic mice, which contain the HBV in their DNA and which are chronic carriers of HBV, were treated with the tiny HBV-fighting packages. Clawson and co-workers chose the dosage and schedule of the drug delivery to the mice based on their cell culture work. Studies with the transgenic mice were performed with John Morrey, Ph.D., at Utah State, under the auspices of an NIH contract which supports testing of antiviral reagents.

"The treatment effects were quite dramatic," Clawson said. "We recorded a greater than 80 percent reduction in the HBV liver DNA, meaning far less virus was being produced, and staining for the virus using antibodies also showed a dramatic decrease in residual viral production. This is significant because there are so few examples of successful in vivo applications of ribozymes against bona fide naturally-occurring, disease-causing organisms."

Clawson believes this cassette is more effective than previous ones for a number of reasons. First, the best target sites were chosen using a "library selection" process. Second, the ribozyme cassette is engineered to cut itself into pieces, thereby freeing the HBV-targeted ribozymes from extraneous sequences that could interfere with their activity. In addition, Clawson's cassette included two distinct trans-acting ribozymes, whereas previous versions included only one. With two trans-acting hammerhead ribozymes in the SNIPAA cassette, twice the amount of "medicine" was present and was delivered over a longer period.

Co-authors on the study were: Wei-Hua Pan, Pin Xin, Departments of Pathology and Biochemistry and Molecular Biology, The Gittlen Cancer Research Institute, Penn State Milton S. Hershey Medical Center, and John D. Morrey, Institute for Antiviral Research, Utah State University.

This work was supported by a research and development contract with Biosan Laboratories/Hexal AG and by a contract from the National Institutes of Health.

This story has been adapted from a news release issued by Penn State.

Back to top



Enzo Biochem (ENZ) Reports On Preclinical Study That Points To Development Of New Compound For Treating Immune Mediated Diseases
Source: Business Wire

SALVADOR DA BAHIA, Brazil--Enzo Biochem, Inc. (NYSE:ENZ) scientists at a medical conference here presented results of a preclinical study in an animal model system evaluating one of the Company's new immunemodulatory agents, glucosylceramide (GC), as a potential therapeutic for treating immune mediated diseases.

GC is a compound that has previously been shown by Enzo scientists and collaborators to modulate specific immune responses by acting on certain immune regulatory cells, and therefore is an important candidate drug in the treatment of various immune mediated diseases, such as Crohn's disease, hepatitis B, hepatitis C and HIV.

The Company believes that GC could be utilized either as a separate therapeutic or as an adjunct or combination treatment with the Company's various other platforms for the management of immune mediated disorders.

The data relating to GC presented at a meeting of the International Association for the Study of the Liver describe a study with laboratory animals that were induced to develop experimental allergic colitis, an immune mediated disorder of the lower intestinal tract resembling Crohn's disease in humans. Four groups of mice were studied, in two of which colitis was induced. One of the colitis-induced groups received daily injections of GC, while the other was given daily injections of normal saline. The two control groups of mice, in which colitis was not induced, were also given daily injections of either GC or saline. The animals were evaluated by standard macroscopic and microscopic colitis condition.

The results showed a marked alleviation of the symptoms of colitis, manifested by significant improvement of macroscopic and microscopic colitis conditions, in the colitis-induced animals treated with GC. In addition, analysis of certain immune cells in the mice showed that the ratios of these cells were altered by the treatment, indicating the immune modulatory effect of the GC.

"These preclinical data strongly support the view that GC has a therapeutic effect in the treatment of experimental allergic colitis in an animal model for Crohn's disease and that the compound functions by acting on certain cells that are central to regulating an immune response," said Dean L. Engelhardt, Ph.D., Executive Vice President of Enzo. "The addition of this compound to our therapeutic development program further expands the scope and extent of Enzo's broad based program in developing new therapeutic products."

Enzo said that a Phase I clinical trial based on these and other preclinical studies of GC is planned. "The study is promising, and we expect to pursue it further in human trials," continued Dr. Engelhardt.

About Enzo
Enzo Biochem is engaged in the research, development and manufacture of innovative health care products based on molecular biology and genetic engineering techniques, and in providing diagnostic services to the medical community. The Company's proprietary labeling and detection products for gene sequencing and genetic analysis, with approximately 200 patents worldwide, are sold to the life sciences market throughout the world. The Company's therapeutic division is in various stages of clinical evaluation of its proprietary gene medicine for HIV-1 infection and its proprietary immune regulation medicines for hepatitis B and hepatitis C infection and for Crohn's disease. The Company also holds a patent covering a method and materials for correcting point mutations or small insertions or deletions of genetic material that would allow for editing and correcting certain abnormalities in genes. For more information visit our website www.enzo.com.

Except for historical information, the matters discussed in this news release may be considered "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. Such statements include declarations regarding the intent, belief or current expectations of the Company and its management. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve a number of risks and uncertainties that could materially affect actual results. The Company disclaims any obligations to update any forward-looking statement as a result of developments occurring after the date of this press release.

Contacts
For: Enzo Biochem, Inc. Steve Anreder, 212-532-3232

Back to top


Nautilus Biotech Announces Progress On Belerofon, An Improved IFN Alpha With Single Amino Acid Sequence Change, Designed To Reduce Frequency Of Injection For Hepatitis C Chronic Infection And Cancer
Source: PRNewswire

PARIS, France- Nautilus Biotech today announced the successful completion of comparative monkey studies between Nautilus proprietary IFN alpha (Belerofon™) and two leading commercial IFN alpha drugs: native IFN alpha and pegylated IFN alpha.

Belerofon™ is a single amino acid variant of natural IFN alpha engineered using Nautilus' proprietary protein evolution technology to create an improved, non-pegylated, non-chemically modified IFN alpha, with longer half-life in serum.

The market (Reference 1) for IFN alpha in the treatment of chronic hepatitis C infection only, reached $2.7 bn in 2003 and is projected to grow to $8.7 bn by 2013 and $12.6 bn by 2018. Pegylated IFN alpha dominates the market based on its improved pharmacokinetics (PK) profile, which translates into lower dosing frequency and higher patient compliance, compared to native IFN alpha.

Initial pre-clinical studies of Belerofon™ in cynomolgus monkeys have recently been completed and show the following positive results:

Low toxicity - Preliminary dose escalation and repeat dosing studies of Belerofon™ in monkeys have shown an absence of adverse clinical or hematological events associated with treatment.

Good biological response - Pharmacodynamic studies using surrogate markers, such as neopterin, MxA and 2'5'AOS, indicate that Belerofon™ is active in vivo and that it triggers the appropriate biological response.

Improved pharmacokinetics - The PK profile observed for Belerofon™ in primates outperformed those obtained for non-pegylated commercial IFN alpha and compared favourably with those obtained for commercial pegylated-IFN alpha, in all parameters measured.

Lower dosing - Belerofon™ showed comparable performance in terms of PK and pharmacodynamics despite 1/10 (w/w) dosage levels being administered compared to pegylated IFN alpha. This is in line with the higher specific activity of Belerofon™ measured in vitro, probably due to the absence of pegylation.

As a result of its improved PK profile and lower dosing, Belerofon™ holds great potential to improve on the current IFN alpha-based therapies for hepatitis C chronic infection, melanoma and kidney cancer.

"The profile shown by Belerofon™ in monkeys fully confirm earlier in vitro and in mice studies, and demonstrate our capacity to effectively design improved proteins. This constitutes a strong validation for our protein evolution approach and its potential to generate significant improvements in therapeutic proteins. We are currently applying this powerful technology to a number of other commercially attractive protein-based pharmaceuticals, including IFN beta (PR Feb 27, 2004, 'Nautilus Biotech announces progress on improved Interferon beta for Multiple Sclerosis)", said Nautilus CSO, Dr Lila Drittanti.

"This milestone reached with Belerofon™ is a key step in our strategy of developing high value, next generation therapeutic protein products. Given its highly competitive profile, as demonstrated in monkeys, Belerofon™ is positioned to move into clinical development. Nautilus Becomes one of the very few directed evolution companies that has demonstrated clear success in the evolution of biopharmaceuticals", said Nautilus CEO, M Vega.

About Nautilus Biotech
Using its proprietary technologies, Nautilus is strongly focused to improving human protein pharmaceuticals and next generation products. Nautilus' corporate headquarters and R&D facilities are in France, while clinical development is driven from its subsidiary in the US.

Additional information concerning Nautilus Biotech can be obtained from either http://www.nautilusbiotech.com/ or by e-mail: contact@nautilusbiotech.com

Reference:
1. includes US, UK, France, Germany, Italy and Spain

NAUTILUS BIOTECH
CONTACT: Contacts: Manuel Vega, CEO, Nautilus Biotech, mvega@nautilusbiotech.com, tel: +33-(0)1-60-87-54-60 or JonWatts, VP Business Development, Nautilus Biotech, jwatts@nautilusbiotech.com, tel: + 44-1488-670-130

Back to top


Homeless Advocate Concerned About Hospital's Suspect Lab Results
Source: Wiley Hall
Associated Press Writer

BALTIMORE (AP) -- When Jeff Singer heard a hospital laboratory may have botched test results for hundreds of HIV and hepatitis C patients, his first reaction was one of horror.

It's hard enough for him to build his clients' confidence in the medical system, said the CEO of Baltimore's Health Care for the Homeless. He already has to address concerns about confidentiality, cost and convenience. Questions about accuracy could give them another reason to avoid testing, Singer said.

Two weeks ago, officials at Maryland General Hospital, an affiliate of the University of Maryland Medical System, said HIV and hepatitis C patients received suspect test results over a 14-month period ending in August 2003. Some 460 patients might have been told they had tested negative when in fact they tested positive - and vice versa.

According to a state inspection report, lab workers manipulated and eliminated machine readings showing that recently completed blood tests might be inaccurate and should be discarded.

The problem came to light after a former employee notified state officials about problems at the lab. She later filed a lawsuit against the hospital, her supervisor and the manufacturer of a blood analyzing machine the lab used.

For Singer, the problems highlighted a broader challenge - providing adequate health care to the city's most needy residents.

"It was pretty dismaying," Singer said. "We encourage our clients to get tested every time we see them. We don't need any discouraging factors coming into play."

An estimated 30,000 people are homeless in Baltimore each year, with about 3,000 people without homes each night, according to city officials.

Singer said there is a high incidence of HIV infection and hepatitis C among the city's homeless population. A recent survey showed that more than 12 percent of the homeless carried the HIV virus, he said.

Another survey found that nearly 50 percent of those seeking help at soup kitchens were infected with hepatitis C. Hepatitis C can cause a chronic liver infection that could eventually lead to liver failure and cancer.

Both HIV and hepatitis C can be spread by sharing drug needles.

"It's a big, big problem, and the problem with the lab tests at Maryland General didn't help," Singer said. "But then we decided to turn a negative into a positive. We said, 'Let's use this crisis to talk to people about testing.' We called the hospital and asked, 'How can we help?'"

Hospital spokesman Lee Kennedy said Maryland General is an urban hospital that treats many poor and homeless patients.

He said the hospital turned to Health Care for the Homeless and similar organizations to find and retest anyone who might have received a suspect test - especially people without homes and phones.

The hospital sent out letters to doctors, churches and social service agencies, Kennedy said. It established a hot line and advertised the number on urban radio stations and in The Baltimore Afro newspaper.

"We've reached out to everything from the Downtown Partnership (a coalition of businesses) to storefront churches," he said.

Kennedy said that by late Tuesday, the hospital had contacted about 70 percent of the patients who received suspect test results. Of those retested, only one result was reversed - a hepatitis C patient originally given a negative result. Kennedy said he did not know many people had been retested.

"Based on the results we've gotten back so far, we're confident that the original results will prove to have been accurate," Kennedy said. He said there was no way to tell whether the hepatitis C patient was given a flawed result from the original test or contracted the disease later.

The hospital announced Monday it had agreed to expand its outreach to include anyone tested on the Labotech blood analyzer. U.S. Rep. Elijah Cummings asked administrators to take the step during a meeting Monday with Maryland General officials.

Kennedy said the lab has not used the blood analyzer since August, when questions about quality control first surfaced. Since then, tests have been sent out to a private lab that he declined to identify.

Back to top



Vencor to Begin E-commerce Distribution of FDA Approved at-Home Hepatitis C, Instant Cholesterol, Allergen and HIV Tests
Source: Business Wire

BEVERLY HILLS, Calif.--Vencor International, Inc. (Pink Sheets:VNCO), announced that it is initiating the distribution of FDA approved at-home tests for HIV and other diseases and conditions throughout the United States of America. Home Access Health Corporation of Hoffman Estates, Illinois, makes the only U.S. Food and Drug Administration (FDA) approved HIV-1 test system. Home Access Health offers a simple at-home collection method combined with an accurate laboratory testing method that insures that a reliable test result quickly and conveniently. Test results and counseling are completely anonymous. Vencor will be offering the Home Access Health FDA approved HIV, Hepatitis C, Instant Cholesterol and Allergy Tests via its E-commerce website www.TestsforHIV.com that will debut within weeks.

This distribution opportunity will provide Vencor with immediate revenues from US sales of FDA approved products while obtaining international regulatory approvals for all previously ordered AccuDx diagnostic products that are being sold in overseas markets.

Safe Harbor Statement
The information contained in this press release, including any "forward-looking statements" within Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 contained herein, should be reviewed in conjunction with the company's annual report, financial filings and other publicly available information regarding the company, copies of which are available from the company upon request. Such publicly available information sets forth many risks and uncertainties related to the Company's business, and such statements, including risks and uncertainties related to that, are unpredictable and outside of the influence and/or control of the company.

Back to top



CombiMatrix and IrsiCaixa Expand HIV RNAi Collaboration to Include Hepatitis C
Source: Business Wire

NEWPORT BEACH, Calif.--March 23, 2004--Acacia Research Corporation (Nasdaq:CBMX) (Nasdaq:ACTG) announced today that its CombiMatrix group is expanding its collaboration with the research group of Professor Bonaventura Clotet, M.D., Ph.D., of the Retrovirology Laboratory irsiCaixa, to conduct the initial efficacy screening of pooled siRNA compounds against the hepatitis C virus.

"We have seen some good results with our HIV compounds and are continuing to pursue this program," said Dr. Amit Kumar, President and CEO of CombiMatrix. "We look forward to expanding our relationship with Dr. Clotet to include testing of our siRNA pools for hepatitis C."

"The Hepatitis C and HIV viruses are two of the most deadly and prevalent viruses of our times," said Professor Bonaventura Clotet, M.D., Ph.D. "We see a growing population of co-infected patients whose morbidity and mortality are significantly increased through synergistic interactions of this combination. We hope our collaboration with CombiMatrix will position CombiMatrix to identify drug targets that will someday eradicate these deadly viruses."

It is estimated that over 4.5 million Americans and over 200 million people worldwide have been infected with hepatitis C. More than 80% develop chronic infections that lead to liver disease. Viral hepatitis C and HIV/AIDS are infectious diseases that are transmitted in many of the same ways and have drastic, long-term medical, economic, and social consequences for those infected with either or both viruses. About one quarter of HIV-infected persons in the United States are also infected with the hepatitis C.

About Retrovirology Laboratory irsiCaixa
The irsiCaixa Foundation is a leading institute and reference center for the research and treatment of Acquired Immuno Deficiency Syndrome (AIDS) in Europe. The Foundation was founded in 1995 with the objectives of advocating, inspiring and spreading medical investigation on (AIDS). The irsiCaixa Foundation Scientific Committee includes many world-renowned experts in the field of HIV research (www.irsicaixa.org/english/about/
a_stru.html#comite).

The activity of the irsiCaixa Foundation is mainly carried out in the Retrovirology Laboratory of the University Hospital Germans Trias i Pujol in Badalona (Barcelona, Spain). The laboratory director is Dr. Bonaventura Clotet, chief of the AIDS unit of the University Hospital. Dr. Clotet received his M.D. of Medicine and Surgery at the Universitat Autonoma de Barcelona, in 1976. He earned his Ph.D. in the investigation of surrogate markers for connective tissue diseases in 1981.

Dr. Clotet has published more than 150 peer-reviewed papers. He is on the Editorial Board of the AIDS Journal and the Journal of the International Association of Physicians in AIDS Care. He has also authored numerous books and chapters on retrovirology and is an expert on siRNA and AIDS.

Professor Clotet is part of the organizing committees of several drug resistance workshops and International Conferences on AIDS, and he is an active member of the Expert Commission for the evaluation of research projects in the National Programme of Health and National AIDS Programme. Dr. Clotet was a co-chair of the Barcelona World AIDS meeting 2002. Information about the irsiCaixa Foundation is available at www.irsicaixa.org.

About Acacia Research Coporation
Acacia Research Corporation comprises two operating groups: Acacia Technologies Group and CombiMatrix Group.

The CombiMatrix group is developing a platform technology to rapidly produce customizable active biochips, which are semiconductor-based tools for use in identifying and determining the roles of genes, gene mutations and proteins. CombiMatrix's technology has a wide range of applications including DNA synthesis/diagnostics, siRNA synthesis, drug discovery, and immunochemical detection. CombiMatrix provides DNA arrays to researchers under the CustomArray™ brand. CombiMatrix's Express Track™ drug discovery program is a systems biology approach, using its technology, to target common viral diseases with siRNA compounds.

The Acacia Technologies Group develops, acquires, and licenses patented technologies. Acacia's DMT technology, which is supported by 5 U.S. and 31 foreign patents, relates to audio and audio/video transmission and receiving systems commonly known as audio-on-demand, video-on-demand, and audio/video streaming, and is used for distributing digital content via several means including Internet, cable, satellite and wireless systems.

Acacia Research-Acacia Technologies (Nasdaq:ACTG) and Acacia Research-CombiMatrix (Nasdaq:CBMX) are both classes of common stock issued by Acacia Research Corporation and are intended to reflect the performance of the respective operating groups and are not issued by the operating groups.

Information about the Acacia Technologies Group and the CombiMatrix Group is available at www.acaciaresearch.com.

Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995:
This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the economic slowdown affecting technology companies, our ability to successfully develop products, rapid technological change in our markets, changes in demand for our future products, legislative, regulatory and competitive developments and general economic conditions. Our Annual Report on Form 10-K, recent and forthcoming Quarterly Reports on Form 10-Q, recent Current Reports on Forms 8-K and 8-K/A, and other SEC filings discuss some of the important risk factors that may affect our business, results of operations and financial condition. We undertake no obligation to revise or update publicly any forward-looking.

Back to top



Canadian Hepatitis C Network - Federal Budget Reaction
Source: Newswire

TORONTO- Community-based hepatitis C organizations expressed shock and dismay that the 2004 federal budget, released today, did not provide for a federal strategy and funding for hepatitis C.

Nearly one quarter of a million Canadians are infected with hepatitis C, and an estimated 5,000 to 8,000 Canadians become infected each year.

The magnitude and complexity of hepatitis C demands a coordinated national strategy engaging all levels of government and all sectors of the healthcare, research, and grassroots community. Because Hepatitis C is still a relative new disease, federal funding along with provincial dollars is essential to develop appropriate programs of care and treatment and to support initiatives in prevention.

The lack of adequate targeted funding is a tragedy not only for those already infected but also for the entire healthcare system, which will need to deal with the increasing burden of hepatitis C. The current costs of treating hepatitis C are conservatively estimated at $500 million per year and will easily double to $1 billion over the next four years.

The initial five-year $50 million program, announced as part of the tainted blood settlement in 1999 and due to end on March 31, 2004, was clearly inadequate. The federal government had received feedback from its own bureaucrats and the hepatitis C community as well as all sectors of healthcare that more funding would be needed to address this devastating infectious disease.

Without a national strategy and targeted funding, we will continue to lose lives and waste dollars at a time when the disease can actually be treated and prevented.

Countries such as Australia, Great Britain and the United States are far ahead of Canada in recognizing and addressing hepatitis C as a national public health crisis. Canada is one of the few developed countries without a national comprehensive hepatitis C strategy. In the 1980s, Canada refused to follow other countries in implementing screening of donated blood for hepatitis C, leading to the infection of approximately 160,000 Canadians. Today, Canada continues to underestimate the risk of hepatitis C and the actions needed to effectively treat and prevent this disease.

The Canadian Hepatitis C Network:
Recognizing the need to speak with a strong, unified voice, Hepatitis C groups from across Canada formed the first-ever Canadian Hepatitis C Network. This network, an umbrella organization for Hepatitis C support groups, believes community-based groups have a vital role in working with governments, healthcare professionals, and other institutions to assure a coordinated, comprehensive strategy for dealing with hepatitis C in Canada.

For further information: Media Contact: Durhane Wong-Rieger, PhD, Secretariat, Canadian Hepatitis C Network, 151 Bloor St. West, Suite 600, Toronto, ON, M5S 1S4, Phone: (416) 969-7435 or cell: (416) 722-2154, www.canhepc.net; durhane@aol.com

Back to top



March 24th, 2004



Funds Cut for Hep C Treatment in Prisons
Senate panel trims $5.9M from governor's proposal
Stacey Range
Lansing State Journal

Prison officials this month will find out how extensive hepatitis C is in Michigan's prisons, but they won't have any money to stop the potentially fatal liver disease from spreading.

A state Senate appropriations subcommittee Tuesday cut $5.9 million proposed by Gov. Jennifer Granholm in the corrections budget for the coming fiscal year. That money was pegged to test and treat prisoners for hepatitis C.

The cut was part of an effort to trim more than $20 million from the $1.8 billion in corrections spending proposed for the 2004-05 fiscal year.

"The funding for hepatitis C was a good idea, but there's just no money for it right now," said Sen. Alan Cropsey, the DeWitt Republican who chairs the Senate Appropriations Subcommittee on Judiciary and Corrections.

Prisoner advocates were outraged, saying that without the money, the state is allowing the disease to spread, putting the lives of inmates and the public at risk of liver disease and other complications.

"There is a disease flourishing at epidemic rates and for us to ignore it is irresponsible," said state Rep. Triette Reeves, a Detroit Democrat who has spent four years pushing for hepatitis C funding.

Further angering Reeves is that the action comes as officials prepare to release results of a three-month survey aimed at determining how extensive the disease is among Michigan's 48,500 prisoners.

Results of the survey, which tested 600 inmates on a voluntary basis, are due to the Legislature by April 1.

"We are going to know soon how big a problem this is, and now we won't have money to treat it," Reeves said. "That's ridiculous."

The survey, mandated by the state Legislature last year at a cost of $30,000, is intended to give officials a better understanding of the virus' prevalence in Michigan's 42 prisons.

A Lansing State Journal special report in September revealed that up to 18,000 prisoners are infected with hepatitis C. Yet only 55 are being treated.

Prison officials say they don't have enough money to treat all infected inmates - a cost that could reach $130 million a year.

Prisoner advocates and health officials from across the country say the state must take measures to test and treat infected inmates to prevent an epidemic that could cost the state millions of dollars to treat if left unchecked.

The blood-borne virus threatens the lives of inmates and the public as prisoners are released and spread it to their friends, families and strangers.

Hepatitis C is transmitted most often through dirty drug needles. But it also can be spread through unprotected sex, nonsterilized hygiene products and occupational hazards for health care and public safety workers.

Hepatitis C is the leading cause of adult liver transplants in the United States. By 2010, hepatitis C will cause more deaths in the United States than AIDS, according to the Centers for Disease Control and Prevention.

Senators left $100 in the budget for hepatitis C testing and treatment, leaving open the possibility that full funding could be restored later.

The subcommittee's two Democratic senators voted against sending the Corrections Department budget to the full committee. Sens. Mike Prusi of Marquette and Michael Switalski of Macomb said they were hopeful the money would be restored.

"This is an important health issue that needs to be addressed," Prusi said after the meeting.

Prison cuts
A Senate subcommittee on Tuesday cut more than $20 million from the Department of Corrections budget:

• $5.9 million -hepatitis C testing and treatment

• $5.3 million - substance abuse testing and treatment

• $5 million - educational and vocational programs

• $2 million - transportation

• $1.5 million - computer system

• $386,000 - administrative savings

• $300,000 - health care

BRUSSELS- Belgian biotech company Innogenetics (INNX.BR: Quote, Profile, Research) said on Thursday patients using its Hepatitis C experimental vaccine showed significantly improved liver fibrosis after a three-year test period.

Innogenetics said in a statement that "liver fibrosis on average showed significant improvement compared to baseline" in in 23 patients over a three-year period period after four course of vaccine injections.

87 percent of the patients either improved or remained stable in the liver fibrosis score.

The company, which also develops test kits for such viruses as the HIV-virus, already reported positive results in October 2002 based on two vaccination courses followed by liver biopsy.

"These three-year study results now show that HCV E1 vaccination was very well tolerated and suggest that such treatment not only halts disease progression towards liver cirrhosis, but also results in fibrosis regression over the longer term," Professor F. Nevens, the principal investigator in the phase IIa clinical study said in a statement.

Back to top

Hepatitis B-Related Hepatocellular Carcinoma
Source: www.gastrohep.com

Young patients with hepatocellular carcinoma often show a later presentation, finds a team of physicians in the April issue of Alimentary Pharmacology and Therapeutics.

In this study, physicians from Hong Kong compared the clinico-pathological features of hepatitis B virus-related hepatocellular carcinoma in young and old patients.

The team assessed 1863 consecutive patients (121 patients were 40 years of age, 1742 patients were over 40) seen at a single institution over a 13 year period.

The team found that young patients presented more frequently with pain, hepatomegaly, and ruptured hepatocellular carcinoma. The older patients presented with ankle edema, ascites and by routine screening.

Liver function, Child-Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher alpha-fetoprotein concentration, larger tumor size, and more frequent metastasis.

The team determined that surgical resection rates were similar between the 2 groups (34% versus 28%).

There was also no difference between the 2 groups in the overall post-resection survival rate.

However, young patients with unresectable disease tended to have shorter survival.

Dr Lam and colleagues concluded, "Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients".

"The screening program should include young hepatitis B virus carriers, even in the absence of cirrhosis".

Aliment Pharmacol Ther 2004; 19(7): 771-7

Back to top



March 27th, 2004



Health officer endorses safe drug site for Victoria
Source:www.canada.com/victoria/timescolonist
Malcolm Curtis
Times Colonist

B.C.'s chief medical health doctor has weighed in on the debate about a safe drug injection site for Victoria, saying that such a facility is needed for the city.

"Speaking as a provincial health officer, I think it would be appropriate," Dr. Perry Kendall said Friday.

The use of illegal drugs administered by needles is an "acknowledged problem" in Victoria, reflected by repeated overdoses and health issues like HIV and hepatitis C, he said.

Diseases are spread through the sharing of needles and drug users are shooting up openly in public areas, Kendall said.

The city's needle exchange centre has more than 2,000 clients, he noted.

Mayor Alan Lowe has mused out loud about making Victoria the second city in North America with an officially supervised injection site, following Vancouver's example.

"We've been hearing about people shooting up in the alleys, people shooting up in people's front yards, around people's businesses and schools," Lowe told a forum on illicit drug use last week.

"In order to deal with some of those problems we do need a safe injection site."

Vancouver's site opened on a three-year trial basis last September in the city's Downtown Eastside. Former Vancouver mayor Philip Owen, who has been travelling around the country to talk about the experience, told the forum of the benefits of the site, used by 500 drug addicts daily.

The facility is part of a "four pillars" approach to dealing with drug addicts -- prevention, harm reduction, treatment and enforcement.

Kendall said early indications suggest the Vancouver experiment is a success; it has resulted in less drug use in public areas and has support from neighbours.

Any bid by Victoria for a similar site would require community support, he said. It will also need to be approved by Health Canada for an exemption under Section 56 of the Controlled Drugs and Substances Act. Vancouver obtained its exemption to conduct a "scientific research pilot project."

Funding would be an issue for any such facility in Victoria with the Vancouver Island Health Authority one likely source of cash, in addition to the provincial Health Ministry. Vancouver received a grant of $1.5 million from Ottawa and $3.2 million from the province.

Earlier this month, the International Narcotics Control Board, an independent United Nations organization, took a swipe at the Vancouver operation. In a report, it criticized the injection site for allowing people to "inject drugs acquired on the illicit market with impunity" and suggested that Canada is violating international drug treaties it signed.

However, Kendall, who co-chaired a task force into the feasibility of such facilities from 1999 to 2001, said it concluded that injection sites meet the requirements of such treaties provided they are used for medical and social service reasons.

Vancouver Mayor Larry Campbell dismissed the UN group. He said it is mostly funded by the U.S., which does not support any "harm reduction" drug programs, preferring to fight a "war on drugs" through enforcement, a policy that Canadian officials feel is not working.

Victoria-Beacon Hill MLA Jeff Bray, who has said Victoria did not need a safe injection site, said Friday he has changed his mind after last week's forum.

Bray said he was surprised by how many people support such a site and now thinks such a facility could be useful. But it may be that several satellite injection sites are needed rather than a central facility that could attract drug users from outside Victoria, he said.

Bray said he wants to see a "needs analysis" done to see what the harm reduction requirements of the city are. Such a study would likely be conducted by the Vancouver Island Health Authority but would have to be supported by Victoria council.

Lowe has not yet indicated when the issue will be discussed by council.

Back to top