Inovio Pharmaceuticals' Synthetic Avian Flu Vaccine Demonstrates Inhibition of Multiple H5N1 Strains in Phase I Trial World Health Organization Told Inovio's Vaccine Generates Four-Fold Increase in HAI Titers in 50% of Subjects Following Intradermal Boost
BLUE BELL, Pa., Nov. 17, 2011 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE AMEX: INO), which is advancing synthetic vaccines to fight cancers and infectious diseases, announced today that a single intradermal (ID) electroporation boost of its SynCon® avian influenza vaccine generated HAI titers against six different, unmatched strains of H5N1 - a distinct new clinical achievement on the global research community's path to develop universal influenza vaccines. This single synthetic vaccine generated a four-fold or greater rise in hemagglutination inhibition (HAI) titers in 50% of boosted subjects in its Phase I clinical study. These results were presented at the 5th WHO Meeting on Influenza Vaccines that Induce Broad Spectrum and Long-Lasting Immune Responses by Dr. Niranjan Sardesai, Inovio's Sr. VP, Research and Development. The invitation-only meeting showcased development programs progressing towards broadly cross-reactive flu vaccines.
Inovio's SynCon® vaccine design process uses a proprietary method to achieve cross-strain or universal protection against the natural and frequent mutations of influenza strains within subtypes. This new interim data, based on the delivery of the H5 HA component of Inovio's avian influenza synthetic vaccine using skin electroporation, follows previously reported positive data from the original vaccinations using this vaccine with intramuscular electroporation delivery.
In the intramuscular part of the study, VGX-3400X generated antigen-specific antibody and cytotoxic T-lymphocyte (CTL) responses against all three antigens that the vaccine was encoded to produce (HA, NA, NP). High levels of binding antibodies were observed in 27 of 28 evaluated subjects (96%). After two vaccinations, 13 of 18 vaccinated subjects (72%) from the first two cohorts developed strong CTL responses to at least one of the vaccine components. The vaccine was found to be generally safe and well tolerated at all dose levels. Reported adverse events and injection site reactions were mild to moderate and required no treatment.
In the intradermal (ID) part of the study - a first-ever flu study using ID electroporation delivery in humans - participants received a booster vaccination using just the H5 HA vaccine component of VGX-3400X. ID electroporation delivers Inovio's synthetic vaccines into skin, which contains large amounts of immune cells such as dendritic cells and macrophages considered most important for generating protective antibodies. Inovio's new ID electroporation device uses a patented miniaturized needle array which creates electroporation conditions uniquely optimized for skin delivery. The goal of this booster vaccination was to determine if ID delivery of the H5 HA construct can increase HAI titers beyond those achieved by the initial intramuscular vaccinations. Twenty participants received the ID booster vaccination. Immune response data measured one month after this boost were presented at the WHO meeting.
Ten of 20 subjects (50%) exhibited a four-fold or greater rise in geometric mean titers (GMT) in the HAI assay (ranging from 1:20 to 1:80 HAI titers) against the Clade 1 A/Vietnam/1203/04 strain. Significantly, a four-fold or greater rise in GMT titers against five other Clade 2 (Clade 2.1, 2.2; 2.3.2; 2.3.4) and Clade 0 H5N1 viruses was also noted in 10-25% of the vaccinated subjects, further demonstrating cross-reactive immune responses in these volunteers. One subject displayed greater than 1:40 HAI titers against all six different H5N1 viruses tested. ID vaccination was found to be generally safe and well tolerated.
HAI measurements from the blood of a vaccinated subject are used to assess the generation of protective antibody responses. A four-fold rise in HAI titers (compared to pre-vaccination) is considered to be an important indicator of immune activation. Generating an HAI titer of 1:20 is generally regarded as a positive vaccine response, with a titer of 1:40 or higher in the blood of vaccinated subjects generally associated with protection against influenza in humans.
The patients boosted with the minimally invasive ID vaccination have been given a second ID booster vaccination. Additional interim data is expected in 1Q 2012.
Speaking at the WHO Meeting, Dr. Sardesai commented, "We are encouraged by the induction of significant HAI titers against multiple, unmatched H5N1 strains after a single intradermal booster vaccination with our synthetic H5 HA vaccine. These data build on the high rates of vaccine-induced antibody and T-cell responses previously elicited by our avian influenza vaccine with intramuscular delivery. We look forward to the next results from this single subtype synthetic vaccine as well as the first data from our multi-subtype influenza vaccine, INO-3510, which combines H1N1 with H5N1. This second influenza study exclusively uses our intradermal delivery system, which accesses the skin's prolific immune system components that are ideal for inducing preventive antibody responses."
Dr. J. Joseph Kim, Inovio's president and CEO, said: "Our goal is an influenza vaccine protective across subtypes and strains. While more testing is needed, these new results are an unprecedented step closer to the Holy Grail of flu vaccine research – creating a universal flu vaccine."
Inovio is advancing its universal influenza vaccine strategy with a second Phase I influenza vaccine study. This trial is assessing INO-3510, Inovio's multi-subtype SynCon vaccine consisting of the H5N1 and H1N1 subtypes delivered exclusively using intradermal electroporation with a goal to provide cross-strain protection against H1N1 and H5N1 viruses. Preliminary safety and immune response data from this 100-subject study are expected in 2Q 2012.
About Inovio Pharmaceuticals, Inc.
Inovio is developing its revolutionary synthetic consensus immunogen technologies to extend the profound medical benefits of the 20th century's immune-system-stimulating vaccines by preventing and treating today's cancers and challenging infectious diseases. Its SynCon® vaccines are designed to provide universal cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza. These synthetic vaccines, in combination with Inovio's proprietary electroporation delivery, have been shown in humans to generate best-in-class immune responses with a favorable safety profile. Inovio's clinical programs include Phase II studies for cervical dysplasia/cancer, leukemia and hepatitis C virus and Phase I studies for influenza and HIV. Partners and collaborators include the University of Pennsylvania, Merck, ChronTech, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that pre-clinical studies and clinical trials may not commence or be completed in the time periods anticipated, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2010, our Form 10-Q for the quarter ended September 30, 2011, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
Investors: Bernie Hertel, Inovio Pharmaceuticals, 858-410-3101
Media: Jeff Richardson, Richardson & Associates, 805-491-8313
SOURCE Inovio Pharmaceuticals, Inc.