A quick analysis of Inovio Pharmaceuticals' (NASDAQ:INO) stock performance history shows plenty of twists and turns -- from the company's early biomedical days to its recent advances in developing a Zika virus vaccine. But this chart shows the story hasn't been great for investors.

Early days

Inovio started out as Biotechnologies & Experimental Research, Inc. in 1983. The company's focus was on creating products for the research marketplace. In 1994, the company changed its name to Genetronics and went public by exchanging shares with Consolidated United Safety Technologies, which was listed on the  Vancouver Stock Exchange. Consolidated United Safety Technologies got its start back in 1979, and was initially named Concord Energy Corp. 

In 1997, Genetronics switched to the Toronto Stock Exchange. A year later, the company listed on the American Stock Exchange. It also remained on the Toronto Stock Exchange until 2003.

The company's focus during much of its early period as a U.S. stock was on electroporation, a technology for introducing DNA and drugs into cells through a brief electrical pulse that causes tiny pores to open in the cell membrane. Genetronics developed drug delivery systems using electroporation and sold electroporation equipment to the research laboratory market. 

In with Inovio

In early 2005, Genetronics acquired Norwegian gene delivery technology company Inovio AS. Shortly thereafter, Genetronics changed its name to Inovio Biomedical Corporation. Electroporation drug delivery remained a core focus of the company.

This period in the stock history wasn't the best for shareholders as Inovio faced several problems.

In June 2007, Inovio announced that it would halt enrollment in two late-stage clinical studies for squamous cell head and neck cancer using its Selective Electrochemical Tumor Ablation (SECTA) investigational therapy. The trials'  independent data monitoring committee expressed concerns about both efficacy and safety. Inovio stock cratered on the news. 

The company also had to restate its 2006 annual and 2007 quarterly financial statements. Inovio's audit committee found issues related to the classification of registered warrants issued by the company. In addition, like nearly every other stock, Inovio stock was hammered by the financial crisis that emerged in 2008. 

Going viral

Viral Genomix began operations in 2000 with a focus on developing DNA-based immunotherapies to treat infectious diseases and cancers. The company was renamed VGX Pharmaceuticals in 2006. On June 1, 2009, Inovio Biomedical merged with VGX Pharmaceuticals, picking up cervical dysplasia vaccine VGX-3100 in the process.  

Inovio's pipeline at that time also included several early-stage and pre-clinical DNA vaccines targeting infectious diseases such as avian influenza, hepatitis C, and HIV. The company still, however, used its electroporation technology for delivery of the DNA vaccines into cells.

Initial excitement among investors about the VGX merger faded quickly, and Inovio stock continued its downward trend. 

Current era

Inovio kept its focus on targeting viruses using DNA vaccines delivered through electroporation. However, the company also continued to study DNA vaccines for treating cancers not caused by viruses, including chronic and acute myeloid leukemia and prostate cancer. 

The stock enjoyed two nice runs over the last four years. In 2013, the company reported encouraging pre-clinical results for its influenza DNA vaccine followed by more good news from a couple of early-stage studies for its HIV vaccine. There was even speculation that Inovio could be bought out. 

More recently, Inovio enjoyed a lot of positive publicity and investor excitement related to its Zika virus vaccine program. In June 2015, the company became the first to win approval from the U.S. Food and Drug Administration (FDA) to initiate clinical studies in humans for an experimental Zika vaccine. 

However, Inovio also encountered an obstacle for its experimental VGX-3100 cervical dysplasia vaccine. In October 2016, the FDA placed a clinical hold on the company's planned late-stage study of the vaccine, requesting additional information about the delivery device. 

What does the future hold for Inovio? The company still hopes to win approval for VGX-3100 and advance cervical cancer vaccine INO-3112, which combines VGX-3100 with DNA-based immune activator encoded for IL-12. Inovio would like to be first to market with a Zika vaccine. The company has come a long way from its Genetronics days -- but there's still a long way to go before Inovio can enjoy the success that its shareholders have long hoped for.

Inovio Biomedical granted VGX Pharmaceuticals a worldwide, nonexclusive license to its DNA delivery technology for intratumoral delivery of a gene to control the growth of melanoma and other cancers. “Bringing together the combination of exciting Inovio technology for drug delivery with VGX’s innovative technology for tumor killing provides a novel and important opportunity to attack and treat previously untreatable cancers,” notes David Weiner, VGX co-founder.

Recent studies in a mouse model of melanoma showed efficient tumor regression after delivering VGX’ gene, VGX 150, with Inovio’s electroporation technology. Electroporation enhances the cellular uptake and expression of genes encoding therapeutic proteins. It may also bypass some of the systemic effects of conventional cancer therapy.

Inovio’s MedPulser® DNA Electroporation Therapy System has been developed to optimize the delivery of DNA into muscle cells. The pulse for intramuscular DNA delivery is designed to create a low voltage field for a long duration. The electrode-needle array on the applicator consists of only one set of opposite pairs for a total of four needle-electrodes.
Under the terms of the agreement, VGX will give Inovio an upfront license fee, payments based on successful completion of clinical and regulatory milestones, and royalties on the sale of products covered by the license. VGX is preparing to file an IND for VGX-150 and expects to initiate a Phase I trial in the first quarter of 2007.

BLUE BELL, Pa. & THE WOODLANDS, Texas--(BUSINESS WIRE)--VGX Pharmaceuticals Inc., a privately held biopharmaceutical company, and ADViSYS, Inc., a privately held biotechnology company, announced today the signing of a definitive merger agreement. All acquired assets of ADViSYS, including its significant pipeline for DNA delivered therapeutics as well as DNA delivery and cGMP manufacturing capabilities will be added to VGX Pharmaceuticals’ newly created Immune Therapeutics division. VGX Immune Therapeutics will focus on developing and commercializing DNA-based vaccines and therapeutics for major indications in the areas of infectious diseases and cancer.

“We are very excited to bring into our fold ADViSYS’ technologies and recognized leaders in the field of DNA manufacturing and delivery,” said Dr. J. Joseph Kim, President and CEO of VGX Pharmaceuticals. “The acquisition of ADViSYS’ strategic assets and expertise allows us unprecedented vertical control over the development of DNA-based therapies. As a result of this merger, VGX Pharmaceuticals will more than double the number of employees as well as synergistically enhance the combined product pipeline. The critical mass gained from this acquisition brings us one step closer to achieving our overall goal of becoming a publicly traded global biopharmaceutical company. We remain committed to creating value for our shareholders by being opportunistic in our strategy for growth via M&A activities.”

VGX Pharmaceuticals will add ADViSYS’ electrokinetic gene delivery (EKD) devices and other proprietary technologies for DNA-based therapeutics. The addition of ADViSYS’ veterinary product pipeline also provides VGX with late-stage/near-market products to balance the product development pipeline and to mitigate early-stage development risk faced by all drug development companies. The porcine-growth hormone releasing hormone (GHRH) application is presently undergoing pre-market regulatory review in Australia. Additionally, the animal health products have the potential to provide significant near-term revenues for VGX and the Company will be actively seeking commercialization partners to better access the global markets.

This transaction marks the second major step in VGX Pharmaceuticals’ global strategy for growth. In November 2005, VGX Pharmaceuticals acquired a controlling interest of a publicly traded pharmaceutical company subsequently renamed as VGX International Inc. (KOSPI: 011000) to expand the Company’s overseas R&D, manufacturing and marketing capabilities.

Details of the Transaction

The merger agreement has been approved by the Boards of Directors of VGX and ADViSYS. Under the terms of the agreement, VGX will purchase all significant assets covering ADViSYS’ intellectual property including plasmid expression vectors, growth hormone releasing hormone and electrokinetic delivery technology. Additionally, VGX will acquire ADViSYS’ R&D and cGMP manufacturing operations at its Woodlands, Texas site.

Following the closing of the purchase agreement, ADViSYS assets will be merged into the newly created VGX Immune Therapeutics, a division of VGX Phamaceuticals, Inc. Kevin W. Rassas, Sr. VP of Business Development will oversee the integration of the two companies and will have operating responsibility over the new division. C. Jo White, Chief Medical officer of VGX will become Chief Medical Officer of the combined company. Gene Kim, Chief Financial Officer of VGX will become Chief Financial Officer of the combined company.

• About VGX Pharmaceuticals :   VGX Pharmaceuticals is a biopharmaceutical company with small molecules and biologics product candidates for the treatment of infectious diseases, cancer and inflammatory diseases. The Company’s clinical development programs include PICTOVIR™ for HIV infection and VGX-410C for chronic HCV infection, both of which are currently in Phase II clinical trials. In addition, Phase I clinical trials will be initiated in 2007 for VGX-150 for the treatment of Melanoma and VGX-1027 for inflammatory diseases. The product candidates and technology programs are protected by the Company’s extensive global intellectual property portfolio. More information about VGX can be found at www.vgxp.com. 

BLUE BELL, Pa.--(BUSINESS WIRE)--VGX Pharmaceuticals Inc. (“VGX”) announced today that it has formed a wholly owned subsidiary, VGX Animal Health, Inc. (“VGX AH”). The newly established company will include the animal health intellectual property and technology that came to VGX as a result of its acquisition of ADViSYS in February of this year. Additionally, VGX AH will have access to VGX’s adaptive electroporation device, Cellectra™ for all animal health applications.

The VGX AH pipeline includes proprietary Growth Hormone Releasing Hormone (“GHRH”) plasmid technology for major food and companion animals. The company’s lead product, Life Tide SW5™ a GHRH porcine product, is currently in registration in Australia. Also in Phase II of development are canine GHRH products for renal failure and cancer related cachexia and anemia. VGX AH has multiple product candidates in Phase I, including indications for equine laminitis and arthritis.

VGX AH will be seeking alliance partners to help in its development and commercialization efforts in major markets throughout the world.

Dr. J. Joseph Kim, President and CEO of VGX Pharmaceuticals, commented, “The formation of VGX AH will allow us to maximize the commercial potential of this important portfolio of animal health technologies, while at the same time allowing us to maintain focus on the continued development and expansion of our core human health biopharmaceutical business opportunities.”

• About VGX Pharmaceuticals :   VGX Pharmaceuticals is a biopharmaceutical company with small molecules and biologics product candidates for the treatment of infectious diseases, cancer and inflammatory diseases. The Company’s clinical development programs include PICTOVIR™ for HIV infection and VGX-410C for chronic HCV infection, both of which are currently in Phase II clinical trials. In addition, Phase I clinical trials will be initiated in 2007 for VGX-150 for the treatment of Melanoma and VGX-1027 for inflammatory diseases. VGX’s research pipelines include new generation of DNA vaccines and therapeutics as well as CELLECTRA™, a proprietary DNA delivery device. The product candidates and technology programs are protected by the Company’s extensive global intellectual property portfolio. More information about VGX can be found at www.vgxp.com.

Blue Bell, PA – July 1, 2007 –  

VGX Pharmaceuticals today announced the promotion of Bryan Byong Jin Kim, D.M.D. to Vice President of Asian Operations. Dr. Kim has been serving as the Senior Director of Corporate Development. Since joining VGX in 2005, Dr. Kim has played an important role in various corporate development operations including the acquisition of VGX International, Inc. as well as the day-to-day management of this publicly-traded biopharmaceutical company in Korea. VGX International was added to a KOSPI 200 index in June, 2007. As VP of Asian Operations, Dr. Kim will oversee and coordinate VGX’s strategic activities in Asia. 

“Bryan has provided an invaluable service to our company,” said Dr. J. Joseph Kim, CEO and President. “As a member of our executive management team, he will continue to play an important role in our overall strategy to become a dynamic global biopharmaceutical company,”  

Dr. Bryan Kim has had extensive experience in building successful organizations throughout his career. Prior to joining VGX, Dr. Kim was a successful private clinician and a Clinical Assistant Professor at the University of Pennsylvania, School of Dental Medicine, where he developed innovative clinical programs and directed important research projects granted by NIDH in microbiology and immunology. 

Dr. Kim holds a Bachelor of Arts degree in Economics and a Bachelor of Science degree in Biological Science, both from University of California at Irvine and a Doctor of Dental Medicine degree from the University of Pennsylvania.

VGX Pharmaceuticals, Inc., a leading developer of novel drugs and vaccines, announced today that it has signed a collaboration and license agreement with VGX International, Inc. The Agreement provides the technical support and manufacturing process technology necessary for VGX International to construct and operate a large-scale cGMP, DNA plasmid manufacturing facility in Korea – its first in Asia. The agreement will also allow VGX Pharmaceuticals additional supply of Phase II clinical through commercial-scale production of cGMP-grade DNA plasmids to meet the increasing demand for its own products and those of its contract manufacturing client organizations around the world.

VGX Pharmaceuticals currently operates a 500-liter scale fermentor in its cGMP, DNA plasmid manufacturing facility in The Woodlands, Texas, and is conducting IND-enabling pre-clinical toxicology studies for three of its DNA plasmid-based product candidates. The candidates include: vaccines for human papilloma virus as a treatment for cervical cancer (VGX-3100); a therapeutic based on human growth hormone releasing hormone (VGX-3200) for cancer-related cachexia; and vaccines for avian influenza (VGX-3400). The Company expects to file Investigational New Drug Applications (INDs) for all three products by June 2008. Additional product candidates are in its robust R&D pipeline.

“Our agreement with VGX International represents the next phase in the expansion of our capabilities to manufacture DNA plasmids for clinical and eventually commercial applications,” said Dr. J. Joseph Kim, President and CEO of VGX Pharmaceuticals. “We will continue to operate world-class manufacturing facilities to meet the increasing demand for our own DNA-based vaccine and therapy product candidates as well as those of our clients.”

Under the terms of the agreement, VGX Pharmaceuticals will license its patented DNA plasmid manufacturing process and cGMP expertise to VGX International exclusively in Asia. VGX Pharmaceuticals will also provide necessary technical support and training for what is planned to be the largest cGMP, DNA manufacturing facility in Asia. The design phase for this facility will commence before the end of 2007.

• About VGX Pharmaceuticals :  VGX Pharmaceuticals is a biopharmaceutical company with small molecule and biologic product candidates for the treatment of infectious diseases, cancer, and inflammatory diseases. The Company’s clinical development programs include PICTOVIR™ for HIV infection, which is in Phase II clinical trials, and PENNVAX™-B, a DNA vaccine for HIV infection, which is in 2 separate Phase I clinical trials. The Company’s lead compound for inflammatory diseases, VGX-1027, is also in Phase I clinical trials. VGX’s research pipeline includes a new generation of SynCon™ DNA vaccines and therapeutics as well as the CELLECTRA™ electroporator, a patented DNA delivery device. The product candidates and technology programs are protected by the Company’s extensive global intellectual property portfolio. More information about VGX can be found at www.vgxp.com.
• About VGXI Inc. :   VGXI Inc. is a leading provider of DNA plasmid manufacturing and development services for DNA vaccine and gene therapy research. The Company has an outstanding track record of success in manufacturing plasmid products under cGMP conditions for client companies’ clinical studies in the US and Europe, and its cGMP and non-cGMP products have passed rigorous reviews by several international regulatory agencies. VGXI’s ability to work with unique requirements and create custom manufacturing solutions is based on its patented manufacturing process, flexible cGMP production facility, and experienced development team. The recently announced research and pre-clinical production services extend the range of high-quality, research grade materials utilizing the same efficient service. This rapid turnaround program provides consistent materials to build a reliable pre-clinical dataset. For information, visit 66.147.244.119/~vgxiico2  

BLUE BELL, Pa.--(BUSINESS WIRE)--VGX Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) accepted the Investigational New Drug (IND) application for its lead anti-inflammatory compound, VGX-1027. VGX-1027 is an orally active, small molecule compound that has shown preclinical efficacy against various inflammatory diseases including Rheumatoid Arthritis (RA) and Type 1 diabetes (T1D).

VGX-1027 is the first of a new class of immune modulators that inhibits the production of several pro-inflammatory cytokines, which are responsible for the damaging effects of inflammatory diseases. Preclinical studies have shown that VGX-1027 is effective in inhibiting these cytokines in cell cultures. They have also demonstrated the product’s efficacy in animal models for several diseases including RA, T1D, psoriasis, and colitis. Its main mechanism of action is the inhibition of NF-kB and the early transient inhibition of P38 MAP kinase signaling pathways.

Inflammatory diseases including RA, T1D, psoriasis, and colitis represent major medical problems. In the U.S. alone, over 2.7 Million people suffer from rheumatoid arthritis. An additional 1 Million Americans suffer from type 1 diabetes, which can be fatal if untreated.

Several blockbuster therapeutic agents dominate the multi-billion dollar RA drug market. However, all of these agents require injection into a patient’s muscle or skin. VGX-1027 offers a distinct advantage over such products because it can be taken as a once-a-day pill. There are very few treatment options available for T1D patients other than insulin, which requires daily injections.

“VGX looks forward to promptly initiating Phase I clinical trials for VGX-1027, which has several potential advantages over other treatment options," stated Dr. J. Joseph Kim, President and Chief Executive Officer.

VGX will conduct Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) in its Phase I studies on VGX-1027. Upon successful completion, the results from these studies will satisfy FDA requirements to commence two Phase II studies: one for RA patients, to be conducted by VGX Pharmaceuticals, and one for T1D patients, to be conducted by its affiliate, VGX International.

Blue Bell, PA - October 1, 2008 - VGX Pharmaceuticals (VGX), a developer of DNA vaccines against cancer and infectious diseases that has entered into a definitive merger agreement with Inovio Biomedical (AMEX: INO), announced today that the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), has awarded the company a contract to develop a preventive HIV DNA vaccine candidate in conjunction with VGX’s constant current electroporation technology for intradermal delivery of DNA vaccines.  The contract was awarded to VGX under the NIAID’s HIV Vaccine Design and Development Teams program and brings together HIV vaccine experts from the University of Pennsylvania School of Medicine and VGX.  The contract, titled “Development of Improved DNA Vaccines and Electroporation Delivery Devices for Prophylactic HIV Vaccines”, provides $23.5 million of funding over seven years, including a base period and follow-on option years.

VGX’s vaccine candidate, PENNVAX™-G (targeting HIV clades A, C, and D), was developed in the laboratory of DNA vaccines pioneer Professor David B. Weiner at the University of Pennsylvania School of Medicine and licensed to VGX. The DNA-based vaccine will be delivered using VGX’s novel intradermal electroporation (ID-EP) technology.  This program expands VGX’s portfolio of candidate HIV vaccines.  The PENNVAX™-B vaccine (targeting HIV clade B) is presently in two Phase I clinical trials.

The funding of VGX and the proposed development program covers preclinical optimization, immunogenicity and challenge studies in animal models, IND-enabling toxicology studies, cGMP-manufacturing of all components of the DNA vaccine and CELLECTRA®-ID-EP device, and the conduct of a Phase I human clinical trial.  cGMP manufacture of the PENNVAX™-G constructs to support clinical trials will be conducted at VGXI, Inc.’s state of the art manufacturing facility.  The principal investigator for the contract is Dr. Niranjan Y. Sardesai, VGX’s Senior Vice President of Research and Development.

“VGX is honored to be chosen for this important contract from the NIH to further develop our electroporation-delivered HIV vaccine.  Dr. Weiner is acknowledged as a pioneer in the field of DNA vaccines, and we are excited to have put together the VGX-University of Pennsylvania development team in partnership with the Division of AIDS at NIAID.  With promising research results to date, we look forward to advancing this DNA vaccine against HIV into clinical studies,” stated Dr. Sardesai.

“This contract substantiates the NIH’s endorsement of VGX’s approach to DNA vaccines and their delivery via our proprietary in vivo electroporation technology,” added Dr. J. Joseph Kim, President and CEO of VGX. “HIV remains a challenging and tremendously important area of medical research, and we value the NIH’s support to further evaluate the immunogenicity and efficacy of our electroporation delivery system and novel preventive HIV vaccine candidate.”

 HIV is transferred by blood, semen, other bodily fluids or breast milk and can lead to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system begins to fail, leading to life-threatening opportunistic infections.  AIDS is a pandemic that has killed an estimated 25 million people in the last 25 years.  In 2007 alone, 33.2 million people were living with HIV, approximately 2.5 million people became newly infected with HIV, and an estimated 2.1 million lost their lives to AIDS worldwide.  While antiretroviral treatments reduce both mortality and morbidity of HIV infection, routine access to such medications is not available in all countries.  The development of effective vaccines for HIV prevention and treatment therefore remains an important goal for global organizations.

 [...]

• About VGX Pharmaceuticals :   VGX Pharmaceuticals is a biopharmaceutical company with small molecule and biologic product candidates for the treatment of infectious diseases, cancer, and inflammatory diseases. The Company’s clinical development programs include PENNVAX™-B for HIV infection, which is in 2 separate Phase I clinical trials, VGX-1027 for inflammatory diseases and VGX-3100, a DNA therapeutic vaccine for cervical cancer delivered by VGX’s electroporator, all of which are in Phase I clinical trials.  In addition, the Company has filed INDs for VGX-3200, a novel DNA therapy that utilizes GHRH for the treatment of cancer cachexia and anemia and for VGX-3400, a DNA preventative vaccine for avian influenza.  VGX has established a vertically-integrated DNA vaccines and therapies platform with extensive capabilities including SynCon™ DNA-based product candidates, the CELLECTRA® delivery device, and access to efficient cGMP plasmid manufacturing.  Vertical control over key aspects of product development has enabled the Company to consistently develop multiple product candidates, from bench-to-IND filing, within 1 year. The product candidates and technology programs are protected by the Company’s extensive global intellectual property portfolio. VGX recently entered into a definitive merger agreement with Inovio Biomedical (AMEX: INO). More information about VGX can be found at www.vgxp.com.
• Company Contact:   Kevin W. Rassas /  Senior Vice-President

[]. said Friday that [Dr. Avtar Singh Dhillon (born 1961)] has become nonexecutive chairman of the company’s board of directors.

Dhillon was initially appointed as executive chairman of the board in 2009, in conjunction with the merger between Inovio Biomedical and VGX Pharmaceuticals, and given the job of providing “continuity and strategic guidance during the integration of the two companies.

Going forward, Dhillon will focus exclusively on his role as chairman and will no longer have executive responsibilities.

“Avtar has provided strong leadership and support during the integration and build up of Inovio Pharmaceuticals (NYSE Amex:INO),” said [Dr. Jong Joseph Kim (born 1969)], the company’s president and CEO. “We look forward to his continued leadership as a non-executive chairman.

Inovio of Blue Bell, Pa., is a developer of therapeutic and preventive vaccines against cancers and infectious diseases.