(INO) Potent hTERT DNA Cancer Vaccine Shows Potential

Mice and monkey study demonstrates robust and broad immune responses; T-cells 18-fold greater than next best peer technology induce tumor-killing function and increase rate of survival Results published in peer-reviewed Cancer Immunology Research

BLUE BELL, Pa., July 24, 2013 /PRNewswire/ — Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that in a preclinical study with two animal models, Inovio’s hTERT (human telomerase reverse transcriptase) DNA cancer vaccine administered with Inovio’s CELLECTRA^® adaptive electroporation delivery technology generated robust and broad immune responses, broke the immune system’s tolerance to its self-antigens, induced T-cells with a tumor-killing function, and increased the rate of survival. Because high levels of hTERT expression are found in 85% of human cancers, regardless of type, Inovio’s cancer candidate holds the potential to perform as a “universal” cancer therapeutic based on these early but unprecedented results. Following this strong preclinical data, Inovio plans to advance its synthetic hTERT cancer vaccine, INO-1400, into clinical trials in 2014.

These results appear in the American Association for Cancer Research journal, Cancer Immunology Research, in a paper entitled: “Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity,” authored by Inovio researchers and collaborators.

Dr. J. Joseph Kim, Inovio’s president and CEO, said: “Inovio has demonstrated in multiple published human studies that our synthetically optimized DNA vaccines delivered with our CELLECTRA delivery system generate best-in-class T-cell immune responses. Here we show that in monkeys our hTERT DNA cancer vaccine generated T-cell immune responses more than 18-fold higher than the previous best results of a peer’s hTERT therapeutic vaccine, which was also a DNA vaccine delivered with electroporation. We are particularly enthusiastic about our vaccine’s potential use as a “universal” cancer therapeutic, given that hTERT is present in the vast majority of cancer types yet rare in normal cells. We plan to develop INO-1400 to treat breast and lung cancers and then expand to other cancer types. This hTERT therapy adds to a growing Inovio oncology franchise spearheaded by our phase II candidate, VGX-3100 for treating HPV-related pre-cancers and cancers, as well as our near clinical INO-5150 to treat prostate cancer.”

Data from both murine and human systems over the past 10 years have demonstrated that TERT-specific cytotoxic T-lymphocytes (CTLs) can recognize and kill TERT-expressing tumor cells in multiple types of cancers. In fact, previous research has shown that breast cancer patients who mounted an hTERT-specific CTL response exhibited significantly longer rates of survival. However, the immune system’s tolerance of cancer cells and their associated antigens produced in the body, which exists to prevent autoimmune diseases, often restricts the immune system’s antitumor response. A major challenge for cancer vaccine development has been to develop approaches to break this tolerance in tumor-bearing hosts. Recent advances in our understanding of antigen presentation and tolerance have led Inovio to create this synthetic DNA vaccine targeting the hTERT antigen.

Inovio constructed a highly optimized synthetic DNA vaccine with multiple proprietary features. Using its novel consensus design approach, two differentiating mutations were incorporated in the vaccine sequence to assist T-cells to more readily recognize self-made hTERT antigens and kill the cancer cells to which these antigens are attached (i.e. break tolerance). In addition, Inovio’s use of a full length antigen DNA sequence encompasses multiple epitopes (parts of an antigen that are recognized by the immune system), potentially helping the immune system by providing multiple opportunities to overcome a tumor’s ability to evade recognition by T-cells.

In the study, Inovio researchers confirmed that vaccination with Inovio’s DNA vaccine delivered by adaptive electroporation induced hTERT-specific cellular immune responses with significantly greater T-cell magnitude compared to prior non-Inovio studies. Over four vaccinations there was a significant dose response, showing the value of multiple vaccinations to increase the immune response and highlighting the limitation of alternative technologies that are not amenable to multiple vaccinations such as viral vectors. Vaccination elicited multiple epitopes not only in mice, but also in monkeys, indicating a broad vaccine-induced immune response.

Study results showed that mice vaccinated with Inovio’s DNA cancer vaccine and then challenged with a cancerous tumor experienced delayed tumor growth and longer overall survival compared with non-vaccinated mice. Mice first challenged with a tumor and then treated with the hTERT DNA vaccine displayed killing activity of the targeted cancer cells expressing the hTERT antigen, with no killing of normal cells that did not express the hTERT antigen. The treated mice experienced significantly smaller tumors and also longer overall survival. Vaccinated animal results were compared to a control group of animals that did not receive Inovio’s DNA cancer vaccine.

In monkeys, whose TERT is 96% similar to human TERT and therefore a highly relevant model for immunotherapeutic vaccine development, the hTERT DNA vaccine elicited strong and broad TERT-specific immune responses and demonstrated the potential to eliminate tumor cells.

Overall, in these studies researchers observed that administration of a synthetic highly optimized hTERT DNA vaccine delivered with electroporation was capable of breaking immune tolerance, and eliciting robust and diverse antigen-specific CTLs, which are responsible for clearing cancerous cells, as well as a potent antitumor response. A favorable safety profile emerged from this study, showing that the vaccine-induced CTLs appeared not to be associated with any major toxicities or organ damage.

The expression of hTERT is thought to correlate with tumor survival and hTERT is associated with 85% of human tumors. Furthermore, there is growing recognition that it may be necessary to target stem cells that produce cancerous cells and recent studies have suggested that cancer stem or stem-like cells also express hTERT. These factors highlight the importance of an effective hTERT-targeting vaccine/immunotherapy and point to the potential benefit of Inovio’s novel cancer vaccine.

About Inovio Pharmaceuticals, Inc.

Inovio is revolutionizing vaccines to prevent and treat today’s cancers and challenging infectious diseases. Its synthetic consensus design approach is intended to help the immune system identify and fight cancer cells or multiple unmatched strains of a mutating virus. These proprietary synthetic vaccines, in combination with Inovio’s electroporation delivery, have in humans generated best-in-class immune responses with a favorable safety profile. Inovio’s lead vaccine, a therapeutic against HPV-caused diseases, is in phase II. Other phase I and preclinical programs focus on HIV, influenza, malaria and hepatitis C virus. Partners and collaborators include the University of Pennsylvania, Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security, University of Manitoba 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, 2012, our Form 10-Q for the quarter ended March 31, 2013, 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.

CONTACTS:
Investors: Bernie Hertel, Inovio Pharmaceuticals, 858-410-3101, bhertel@inovio.com
Media:     Jeff Richardson, Inovio Pharmaceuticals, 267-440-4211, jrichardson@inovio.com