|Roche (SIX: RO, ROG; OTCQX: RHHBY) and Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced that they have entered into an exclusive worldwide license agreement to research, develop and commercialize Inovio’s highly-optimized, multi-antigen DNA immunotherapies targeting prostate cancer and hepatitis B. The licensed compounds are currently in preclinical development and have generated robust T-cell responses in animal models.Roche acquired an exclusive license for Inovio’s DNA-based vaccines INO-5150 (targeting prostate cancer) and INO-1800 (targeting hepatitis B) as well as the use of Inovio’s CELLECTRA® electroporation technology for delivery of the vaccines. Roche also obtained an option to license additional vaccine opportunities in connection with a collaborative research program in oncology. Roche and Inovio will collaborate to further develop INO-5150 and INO-1800.
Under the terms of the agreement, Roche will make an upfront payment of USD $10 million to Inovio. Roche will also provide preclinical R&D support and payments for near-term regulatory milestones as well as payments upon reaching certain development and commercial milestones potentially up to USD $412.5 million. Additional development milestone payments could also be made to Inovio if Roche pursues other indications with INO-5150 or INO-1800. In addition, Inovio is entitled to receive up to double-digit tiered royalties on product sales.
Commenting on the deal, Hy Levitsky, Head of Cancer Immunology Experimental Medicine at Roche, said: “At Roche we are always interested in finding first-in-class and best-in-class therapies that may become the next generation treatments for patients with different types of cancer. INO-5150 will allow promising combination opportunities with the Roche portfolio, particularly with our emerging cancer immunotherapy molecules.” Janet Hammond, Head of Infectious Diseases Discovery & Translational Area at Roche, added: “We are very excited to have this potentially very important and novel mechanism of action as part of our portfolio as we seek to address the significant unmet medical need in chronic hepatitis B infection.”
“This partnership represents an important milestone in Inovio’s growth and maturing product portfolio. Roche brings to our immunotherapy candidates its leadership position and track record for developing and marketing innovative first-in-class therapies,” said Dr. J. Joseph Kim, Inovio’s President and CEO. “Collaborating with the world’s preeminent oncology development partner allows us to rapidly advance two of our promising near-clinical stage immunotherapy products from our product pipeline as we continue development of our phase II lead product, VGX-3100, for treatment of HPV-related cancers and dysplasia.”
About INO-5150 for Prostate Cancer
Inovio’s SynCon® DNA vaccine for prostate cancer was designed with PSA and PSMA synthetic consensus immunogens based on human and macaque sequences, resulting in amino acid sequences that differ slightly from the native human protein. In humans, this novel approach is utilized to help the body’s immune system recognize cancerous cells created in the body as ‘foreign’, overcoming the body’s self-tolerance of these cells and mounting an immune response to clear them.
About INO-1800 for Hepatitis B
Inovio has reported preclinical data showing its hepatitis B vaccine (INO-1800) generated strong T-cell and antibody responses that led to the elimination of targeted liver cells in mice. These results indicate this DNA vaccine’s potential to treat hepatitis B infection and prevent further development of the infection into liver cancer in humans.
In a preclinical study, researchers found the vaccine-specific T-cells exhibited a killing function, and could migrate to and stay in the liver and cause clearance of target cells without evidence of liver injury. This was the first study to provide evidence that intramuscular immunization can induce killer T-cells that can migrate to the liver and eliminate target cells.
To provide worldwide rights to Roche, Inovio has re-acquired its hepatitis B, Asian-country rights from Inovio’s international affiliate.
Prostate cancer is the second most frequently diagnosed cancer of men. Nearly three-quarters of the registered cases occur in developed countries. Accounting for nearly 300,000 deaths each year, prostate cancer is the sixth leading cause of death from cancer in men. The development of a new treatment for prostate cancer would be a significant medical advancement given that present treatment options (surgery, radiation and hormone deprivation), while somewhat effective, all carry deleterious side effects and are often not a long-term cure.
Hepatitis B and Liver Cancer
Liver cancer is the third most common cancer and the most deadly, killing most patients within five years of diagnosis. About 600,000 new cases arise each year. One of the major causes and risk factors for liver cancer is infection by hepatitis B.
About Inovio Pharmaceuticals, Inc.
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Since it became a global issue during World War II, researchers and scientists have been struggling to develop a vaccine for Dengue fever. To date, there has been no success in eradicating this disease. Before we get to the specifics of the challenges this disease presents, let’s cover the symptoms related to this tropical disease.
Dengue fever is a viral disease that is typically transmitted through a mosquito bite. It thrives in warm, wet climates, hence the greater number of reported cases in Malaysia, Mexico, the Caribbean and, in more recent times, Florida. It is characterized by a fever, headache, muscle/joint pain and a skin rash similar to that of the measles. Dengue is rarely fatal, but because there is currently no vaccine, standard treatment simply consists of IV fluids to prevent dehydration and, in some cases, a blood transfusion.
Why has it been so hard to come up with a vaccine? Being a viral disease, it has mutated over time to its current form that involves four different serotypes. Infection with one serotype generates antibody production for life-long protection, but only against that particular strain. The patient will experience only short-term protection against the other three serotypes. The research community believes that this is most likely due to viral interference. Thus, a vaccine must be tetravalent and offer strong resistance to all four strains simultaneously to be effective.
Current studies around the development of a vaccine include chimerization with yellow fever 17D vaccine strain, combinations of defined mutations/deletions and chimeras and chimerization with dengue 2 PDK53 virus, attenuated by cell culture passage. Due to the fact that it may take up to twelve (12) months for sufficient antibody response, three-part immunization schedules have been developed. Unfortunately, one inoculation will not protect an individual from all four serotypes and could actually enhance the disease if infection occurs between the first and last immunization.
The World Health Organization estimates ~30 million new cases of Dengue fever every year, with a fair percentage of those infected being children. Eradicating this disease through immunization has become somewhat of a Holy Grail for today’s modern scientist.
A new potential vaccine for malaria is gaining media attention after successful pre-clinical trials in small animals and non-human primates. Until now, the most effective malaria vaccine in human clinical trials has been GSK’s RTS,S vaccine. Their vaccine demonstrated a 50% efficacy in children between the ages of 5 and 17 months and only a 30% efficacy in infants aged 6 to 12 weeks.
However, a recent article published in the American Society for Microbiology’s peer-reviewed journal, Infection & Immunity, titled “Inducing humoral and cellular responses to multiple sporozoite and liver-stage malaria antigens using pDNA” introduces a vaccine that could give the RTS,S vaccine a run for its money.
The vaccine in from this study was developed by Inovio Pharmaceuticals (Blue Bell, PA) and is one of their advanced SynCon® DNA Vaccines. Along with their collaborators, the researchers at Inovio designed the DNA vaccine to incorporate four sporozoite and liver-stage malaria antigens that play a critical role in the control or elimination of malaria infection. The doses were administered using their CELLECTRA® electroporation device which injects the vaccine into the tissue and then sends out small electrical pulses. The pulses create small pores in the cell membranes of nearby cells that allow the plasmid DNA to enter.
Dr. J. Joseph Kim, President and CEO of Inovio, said, “Published data from two clinical studies has demonstrated that Inovio’s products generated best-in-class T-cell immune responses. Using the same synthetic vaccine technology that produced clinical candidates against HPV, HIV, and influenza and achieved potent antibody and T-cell immune responses against these targets, we have now generated strong immunology data with our malaria vaccine in non-human primates. We are excited to advance toward the very important healthcare goal of conquering malaria.”
The vaccine demonstrated strong and durable antibody and T-cell immune responses. Not only that, the vaccine-produced T-cells also displayed the ability to kill and eliminate malaria-infected cells. Additionally, the researchers found evidence of vaccine-induced CD8+, or “killer T-cells”, in the liver which have proven essential for rapid elimination of liver-stage malaria parasites. Confident in their data thus far, Inovio has announced they will be initiating a Phase I/IIa clinical trial of the investigational vaccine in 2014. Approximately 30 individuals will be enrolled to participate in this “challenge trial” involving controlled human malaria infection.
In addition to their malaria vaccine, Inovio has achieved strong results from a Phase I trial of their therapeutic vaccine against HPV-caused pre-cancers and cancers, as well as their universal flu vaccine.
(For more information on malaria and other malaria vaccines undergoing development – click here)
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What advancement in the field of DNA Vaccines do you think has made the biggest impact? Do you think there is anything else that could provide more effective delivery of DNA Vaccines than electroporation? Tell us what you think in the comments below!
In development since 2001, the HIVBr18 DNA vaccine developed at the Medical School at the University of Sao Paulo (USP) in Brazil may prevent transmission of human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome (AIDS).
The DNA Vaccine encodes 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes capable of eliciting broad CD4(+) T cell responses in multiple HLA Class II transgenic mice. The team of scientists at USP started conducting mouse studies in 2006. Because rodents are not naturally susceptible to HIV/AIDS, the scientists developed their own method – a smallpox family virus containing HIV antigens. The researchers infected the mice with the modified virus and administered the DNA vaccine. The results were a reduction of infection that was fifty times greater than the control group.
The next step for researchers is to carry out studies of the vaccine on non-human primates. Specifically, the USP scientists will have access to a colony of 24 rhesus monkeys being provided to them by the country’s Butantan Biomedical Research Institute.
Rhesus monkeys are a good natural animal model for the study of HIV because their immune systems are quite similar to that of humans. They are also susceptible to simian immunodeficiency virus which is suspected to be a precursor to HIV. The study will take approximately two years to complete.
“Our goal is to test various immunization methods to select the one capable of inducing a stronger immunological response and thus be able to test it on humans,” lead investigator Edecio Cunha Neto told reporters.
While the researchers do not expect that their vaccine will entirely cure HIV, there is good preclinical evidence to suggest that human-to-human transmission and the development of AIDS could be prevented. If successful in the upcoming trial, this DNA vaccine could provide a sustainable state of maintenance to infected individuals and prevent infection in others.
The University is currently seeking funding from the private sector to proceed with human clinical trials sometime in the next three years.
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Other articles you might find interesting:
- Coridon’s HPV DNA Vaccine Shows Promise in Preclinical Trials
- 100% HIV Protection in Mice Using Gene Therapy
- DNA Vaccine Delivery Delimma Solved? Introducing the Painless Patch