ImVacS 2012: Hepatitis C vaccine show promise

Press release posted 8/15/12 on Science Alert.com.au. Data presented on 8/13 at the Immunotherapies and Vaccine Summit (ImVacS) in Cambridge suggests a breakthrough in Hepatitis C vaccine research. Researchers took into account the highly error prone replication of HCV when creating this vaccine. By developing a vaccine that has only the most essential and highly conserved parts of the major viral surface protein, the body elicits antibodies that prevent both closely and distantly-related hepatitis C viruses from entering the cell and causing infection. Great promise involves great data however, of which we wait. 

Hep C vaccine breakthrough
 
WEDNESDAY, 15 AUGUST 2012

Hepatitis C affects around 200 million people around the world, and has a great ability to change its structure and evade the immune response, making it hard to vaccinate against. But the new vaccine candidate only contains the most essential, conserved parts of the viral surface protein, so it works on a variety of strains.

Currently undergoing formal preclinical studies, the vaccine is the result of breakthrough work done by Associate Professor Heidi Drummer with her team from the Institute’s Centre for Virology.

Hepatitis C affects around 200 million people around the world – a preventative vaccine has the potential to have a significant global health impact.

Associate Professor Drummer and her team have overcome a major hurdle in HCV vaccine research, developing a vaccine candidate that protects against a number of different HCV strains.

“Hepatitis C has a great ability to change its structure and evade the immune response. This makes vaccine development challenging,” Associate Professor Drummer said.

“Our vaccine is unique as it contains only the most essential, conserved parts of the major viral surface protein, eliciting antibodies that prevent both closely and distantly related hepatitis C viruses from entering cells, thereby preventing infection.”

Associate Professor Drummer unveiled the details about her HCV vaccine project at the prestigious Immunotherapeutics and Vaccine Summit (ImVacS) in Cambridge, Massachussets on August 13

Okairos AG begins mid-stage trial of preventative vaccine for HCV...

Posted 3/14/12 via Bloomberg.com .  Swiss company Okairos AG begins mid-stage trial looking a what it hopes to be the first preventative vaccine for the Hepatitis C virus. 

Former Merck Unit Works on First Vaccine for Hepatitis C
By Makiko Kitamura - Mar 14, 2012 1:00 AM PT

Okairos AG, a biotechnology business that Merck & Co. (MRK) sold to venture capital funds in 2007, is seeking to produce the first preventive vaccine for hepatitis C, challenging makers of treatments for the disease.

Okairos has begun a mid-stage study, funded by the U.S. National Institutes of Health, of a gene-based vaccine designed to stimulate the body’s immune system to prevent hepatitis C from taking hold, Chief Operating Officer Tom Woiwode said in a phone interview from the company’s Basel, Switzerland, headquarters.

No vaccine exists for hepatitis C, which affects as many as 170 million people globally, putting them at risk of developing liver cancer, according to the World Health Organization. The growing population of patients infected with the virus spurred Gilead Sciences Inc. (GILD)’s decision in November to buy experimental hepatitis C-treatment maker Pharmasset Inc. for $10.8 billion and Bristol-Myers Squibb Co. (BMY)’s acquisition in February of Inhibitex Inc. for $2.5 billion.

“This could change the landscape quite a bit,” said Les Funtleyder, a health-care strategist and portfolio manager at Miller Tabak & Co. in New York. “In theory, if you could vaccinate everyone, you’d need a lot less drug.” Funtleyder said he isn’t aware of any other preventive vaccines in development.
Disease Transmission

Okairos’s vaccine would target those who may be at risk of infection. The disease is most commonly transmitted through contaminated blood transfusions, organ transplants, contaminated syringes and needle-injected drug use, according to the WHO.

Most preventive vaccines stimulate the production of antibodies, molecules produced by the immune system as part of the body’s defenses. Development of Okarios’s vaccine was triggered by studies of patients with early-stage hepatitis C, of whom about 20 percent spontaneously clear the virus and avoid advancing to the chronic phase, Woiwode said.

Researchers have found those patients tend to have a strong response in the blood’s T cells, Woiwode said. Armed with that knowledge, Okairos developed technology that delivers genetic material to stimulate T cells, the white blood cells that help the body fight diseases.

This approach contrasts with most other vaccines, which stimulate an antibody response, Woiwode said.

“We’ve opened up a new path that will allow us to address a number of diseases, hepatitis C being the first one,” he said in the interview yesterday.

Even if a vaccine is approved, medicines are needed to treat patients already infected, Miller Tabak’s Funtleyder said.

Industry Projects
Merck and Vertex Pharmaceuticals Inc. (VRTX) won approval last year for the first new therapies for hepatitis C in almost a decade. Johnson & Johnson (JNJ), a partner in the Vertex drug, is also cooperating with Swedish drugmaker Medivir AB (MVIRB) on a hepatitis treatment. Basel-based Roche Holding AG (ROG) agreed in October to buy Anadys Pharmaceuticals Inc., another maker of experimental medicines for hepatitis C, for about $230 million.

Profectus Biosciences Inc., a Baltimore-based vaccine manufacturer, is also developing a drug that prevents patients with early-stage hepatitis C from advancing to the chronic stage. The company plans clinical trials of the product in 2013.

Investors in Okairos, which is also developing malaria, cancer and flu vaccines, include Boehringer Ingelheim Venture Fund, Life Sciences Partners, Novartis Venture Funds and Versant Ventures. The Swiss company has also received grants from the European Union and the Bill and Melinda Gates Foundation.

The company is in discussions with potential partners for marketing the vaccine, Woiwode said.

“I have no doubt that if this Phase 2 study is successful, there will be no shortage of interest to work with us to bring this to the market globally,” he said.
To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Nuron Biotech Expands Portfolio With License of Therapeutic and Prophylactic Hepatitis Vaccine Candidates...

Nuron Biotech Expands Portfolio With License of Therapeutic and Prophylactic Hepatitis Vaccine Candidates

EXTON, Pa., Mar 05, 2012 (BUSINESS WIRE) -- Nuron Biotech Inc. today announced it has acquired an exclusive license of technology and product rights relating to Chimigen(R) multi-antigen vaccines from Akshaya Bio Inc., of Edmonton, Alberta, Canada, for the hepatitis B virus (HBV). Nuron Biotech has also acquired an exclusive option to license prophylactic and therapeutic products for the hepatitis C virus (HCV). Currently, no therapeutic vaccine for HBV and no prophylactic vaccine for HCV exist on the market. Financial terms were not disclosed.

"These licenses and options fit incredibly well with Nuron Biotech's strategy of identifying and in-licensing life-saving and life extending product candidates in the areas of vaccines and biologics," said Shankar Musunuri, Ph.D., MBA, Chief Executive Officer of Nuron Biotech. "This chimeric vaccine platform (Chimigen(R) technology), which is used in generating both therapeutic and prophylactic vaccines, is advanced to the point where we can expect to transition our first candidate into a Phase 1 clinical trial in 2013."

"This unique technology provides Nuron Biotech with the capability to develop a highly efficient vaccine for the treatment and prevention of HBV and HCV by inducing both cellular (T cell) and humoral (B cell, antibody) immune responses to clear disease," said Robert G. Gish, M.D., Chief of Clinical Hepatology and Professor of Clinical Medicine, University of California, San Diego. Dr. Gish is also a member of the Scientific Advisory Board for Nuron Biotech. "HBV and HCV are life-altering and potentially fatal diseases, and this technology may offer a break-through for a new generation of novel therapies and preventative vaccines for patients around the world."

Currently, 380 million people worldwide are infected with chronic HBV, which is not curable by any known therapy. More than 170 million people are infected by HCV, which is one of the leading causes of chronic liver disease, cirrhosis, liver transplantation and hepatocellular carcinoma.
About Chimigen(R) Vaccine Technology

The bifunctional nature of the chimeric multi-antigen vaccine technology represents a unique and direct approach in the therapy of chronic infectious diseases by specifically targeting antigen-presenting cell receptors with the most effective combination of viral antigen(s) and novel antibody tail fragment, the chimeric antigen. This technology offers to induce a balanced cellular as well as humoral immune response to attack chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) and may offer protection from infection.

About Nuron Biotech
Nuron Biotech is developing novel biologics and vaccines for the prevention and treatment of chronic neurodegenerative and infectious diseases. Our team of industry veterans is advancing products to meet unmet medical needs in the areas of multiple sclerosis, Alzheimer's, hepatitis B and hepatitis C for patients across the globe. Our lead drug candidate, NU100 (interferon beta-1b), is a new chemical entity currently in Phase 3 for patients with multiple sclerosis. www.nuronbiotech.com .
SOURCE: Nuron Biotech Inc.

Transgene considers change study design after 3 patients develop interferon-related blood disorders in dosing with TG4040.

Article posted today from Bloomberg on 3 patients in Transgene vaccine trial (TG4040) that developed blood disorders normally associated with interferon. TG4040 was given with peg-inf and RBV in their clinical trial - it's not clear whether the blood disorders were due to the vaccine or the interferon component of the therapy.

Transgene Says 3 Patients in Hepatitis Trial Had Blood Disorders
October 11, 2011, 1:57 PM EDT

Oct. 11 (Bloomberg) -- Transgene SA said three patients in a mid-stage trial for its TG4040 vaccine to treat chronic hepatitis C developed blood disorders, prompting the biotechnology company to propose changing the study’s design.

One patient suffered aplastic anemia and two others developed thrombocytopenia, including one with neutropenia, after interferon therapy and not during direct treatment with TG4040, said Transgene, whose biggest shareholder is the French family headed by Alain Merieux, in an e-mailed statement today. TG4040 is used in combination with pegylated interferon alpha and ribavirin in the study, which included 154 people.

“A possible relationship with TG4040 cannot be today formally ruled out and is under active investigation,” the company, based near Strasbourg, France, said in the statement. “The company has decided to submit an amendment to the study design so as to avoid further exposing patients to possible similar adverse events.”

No such side effects occurred in an early-stage trial involving 39 patients who hadn’t received treatment for the disease, Transgene said. These severe events are possible though rare with the standard treatment alone, the company said.

A voicemail message left for Elisabetta Castelli, a Transgene spokeswoman, wasn’t immediately returned after business hours.

Aplastic anemia is a condition in which bone marrow doesn’t produce enough new blood cells. Thrombocytopenia is a decrease in platelets, a component of blood that aids clotting, and neutropenia is a decrease in neutrophils, the most common type of white blood cell.

Hepatitis C is caused by a virus that leads to chronic disease in 75 percent to 85 percent of those infected, according to the U.S. Centers for Disease Control and Prevention in Atlanta. About 170 million people carry the virus worldwide, the CDC said on its website.

--Editor: Kristen Hallam, Chris Staiti

To contact the reporter responsible for this story: Andrea Gerlin in London at agerlin@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Inovio Pharmaceuticals and VGX International to Advance Therapeutic Hepatitis C and Hepatitis B Synthetic Vaccines into Clinical Studies

New partnership to develop a therapeutic HCV vaccine - Inovio and VGX will own both the vaccine and the delivery system to administer it

BLUE BELL, Pa., Oct. 10, 2011 /PRNewswire via COMTEX/ -- Inovio Pharmaceuticals, Inc. a leader in the development of synthetic vaccines against cancers and infectious diseases, announced today that it has entered into a product development collaboration agreement with its affiliate, VGX International Inc. to co-develop Inovio's SynCon® therapeutic vaccines for hepatitis B and C infections.

Under the terms of the agreement, VGX International will receive marketing rights for these vaccines in Asia, excluding Japan, and in return will fully fund IND-enabling and initial phase I and II clinical studies. Inovio will receive payments based on the achievement of clinical milestones and royalties based on sales in the licensed territories and retains all commercial rights in all other territories.

The first product to enter clinical testing will be a synthetic multi-antigen hepatitis C virus (HCV) vaccine covering genotypes 1a and 1b and targeting the antigens NS3/4A, which includes HCV nonstructural proteins 3 (NS3) and 4A (NS4A), as well as NS4B and NS5A proteins. The vaccine will be delivered with Inovio's CELLECTRA® delivery device. IND-enabling toxicology tests will be conducted in 1H 2012, with the intent being to initiate a phase I clinical study in late 2012. The target population for the vaccine clinical trials will be HCV infected individuals.

Supporting this product development advancement are positive preclinical results from Inovio's novel SynCon® vaccine targeting NS3/4A, which were published in the journal Molecular Therapy in the paper, "Hepatitis C Virus NS3/NS4A DNA Vaccine Induces Multi-epitope T Cell Responses in Rhesus Macaques Mimicking Human Immune Responses." Following immunization, rhesus macaques mounted strong HCV-specific T cell immune responses strikingly similar to those reported in patients who have cleared the virus on their own. The responses included strong NS3-specific interferon- (IFN-) induction, robust CD4 and CD8 T cell proliferation, and induction of polyfunctional T cells. The study was funded in part by a $2.8 million PA CURE grant received by Inovio and its collaborators in 2010 to develop this multi-antigen synthetic HCV vaccine.

"Hepatitis B and C are a major global health problem, with about 470 million people infected worldwide. As a development leader of synthetic vaccines, we are pleased to collaborate with our affiliate VGX International to advance our global, multi-antigen HCV vaccine into the clinic. This latest development is an integral part of Inovio's multi-pronged approach to develop our therapeutic hepatitis vaccine pipeline," stated Dr. J. Joseph Kim, President and CEO.
Inovio has an ongoing open label Phase II clinical study with ChronTech Pharma AB to test the effect of a DNA vaccine (ChronVac-C®) encoding for NS3/4A protein (genotype 1a) administered by Inovio's MedPulser® electroporation delivery device followed by the standard of care (SOC) drug treatment using interferon and ribavirin. In an earlier phase I study, 5 of 6 participants (83%) who received the vaccine along with SOC cleared the virus. SOC drug treatment alone in patients infected with HCV genotype 1 results in clearance of the virus in 40-50% of patients. Interim results from this phase II study are expected in 2012.

Inovio previously announced a research collaboration with ChronTech Pharma AB and Transgene S.A. to test the immunogenicity of a DNA/electroporation prime - MVA boost approach against HCV by combining two promising, previously studied clinical candidates. A Phase I clinical study is anticipated to start in Q4 2011.

Under the same agreement, Inovio and VGX International will also co-develop Inovio's SynCon® therapeutic vaccine for hepatitis B virus.

Epixis HCV vaccine looks effective even with mutated HCV variants in murine studies...

From Reuters.... French scientists have developed an experimental preventative vaccine that has shown to activate a robust immune response. The vaccine was shown to prevent infection with several mutated variants of the HCV virus in murine studies.

By Ben Hirschler

LONDON | Wed Aug 3, 2011 5:27pm EDT

LONDON (Reuters) - French scientists have developed a novel hepatitis C vaccine that may offer the first effective way to prevent an infection that can cause chronic liver disease and cancer.

There is currently no available vaccine for hepatitis C, though some companies are developing so-called "therapeutic vaccines," which are designed to help patients who are already infected.

The latest experimental shot has been tested successfully on mice and monkeys, but not humans, and has been shown to activate a broad response from immune system proteins called neutralizing antibodies.

The antibodies fought off multiple variants of the hepatitis C virus in tests, suggesting the new vaccine should be effective even after the virus mutates, the researchers reported on Wednesday.

Neutralizing antibodies play a central role in most existing vaccines against other diseases, but harnessing them in hepatitis C has previously proved elusive. Work to date on therapeutic vaccines has focused on another immune system mechanism known as T-cells.

"For a preventative vaccine, neutralizing antibodies are absolutely essential, and for a therapeutic product they would also be a big advantage," David Klatzmann, a member of the research team, told Reuters.

About 130 million to 170 million people worldwide are chronically infected with hepatitis C virus, and more than 350,000 die from hepatitis C-related liver diseases each year, according to the World Health Organization.

Unlike hepatitis A or B, most people with hepatitis C develop chronic disease because their bodies are unable to get rid of the virus. The condition is spread by exposure to infected blood.

Interferon and ribavirin-based therapy has been the mainstay of treatment, although recently Vertex and Merck have both launched promising new medicines that are tipped to become multibillion-dollar-a-year sellers.

Commercial interest in hepatitis C vaccines has been more muted. French biotech company Transgene and Austria's Intercell are both testing therapeutic versions, but the main markets for a preventative shot would be in the developing world, which is less attractive for Big Pharma.

Commercial rights to the new vaccine are held by French start-up Epixis, which is being acquired by an undisclosed U.S. biotech company.

Epixis CEO Charlotte Dalba said she hoped that initial human trials of the vaccine could start in 2012, provided funding was in place.

The experimental vaccine uses virus-like particles, which resemble viruses but are non-infectious because they don't contain any viral genetic material. Details of its development were published in the journal Science Translational Medicine.

In an accompanying commentary, Ranjit Ray of Saint Louis University said the work to date on mice and macaque monkeys showed significant progress, though "many questions still remain."

SOURCE: bit.ly/qX39WK Science Translational Medicine, August 3, 2011.