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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.

OVERVIEW

• We were incorporated in British Columbia, Canada on August 8, 1979 under the name of Concord Energy Corp. We changed our name to United Safety Technology Inc. on February 17, 1988, to Consolidated United Safety Technology Inc. on January 3, 1990, and then to Genetronics Biomedical Ltd., on September 29, 1994. On June 15, 2001, the Company completed a change in its jurisdiction of incorporation from British Columbia, Canada into the state of Delaware. The change was accomplished through a continuation of Genetronics Biomedical Ltd., a British Columbia Corporation, into Genetronics Biomedical Corporation, a Delaware corporation. We carry on our business through our operating subsidiary Genetronics, Inc., a California corporation. Genetronics, Inc. was incorporated in California on June 29, 1983. Genetronics, Inc. had a subsidiary called Genetronics S.A., which was incorporated in France on January 30, 1998. Genetronics S.A. was formed primarily to manage clinical trials that were being conducted in France. Effective May 2000, the Company closed the operations of Genetronics S.A. and subsequently sold its investment for nominal consideration to Geser S.A., a company owned by Genetronics S.A.’s former General Manager. All of our business activities are conducted through Genetronics, Inc. Unless otherwise indicated, all references to Genetronics or the Company refer to Genetronics Biomedical Corporation and Genetronics, Inc. on a consolidated basis.
• The Company’s originally filed Form 10-K included consolidated financial statements for the year ended March 31, 2001 prepared in accordance with Canadian generally accepted accounting principles. As a result of the change in its jurisdiction of incorporation, the Company is filing this amendment to Form 10-K whereby its consolidated financial statements will be presented in accordance with U.S. GAAP. In addition, selected Consolidated Financial Data and Management’s Discussion and Analysis have been modified to address the results of operations as presented in accordance with U.S. GAAP.
• We are a San Diego-based drug and gene delivery company specializing in developing technology and hardware focused on electroporation. Electroporation is the application of brief, controlled pulsed electric fields to cells, which cause tiny pores to temporarily open in the cell membrane. Immediately after electroporation, the cell membrane is more permeable to drugs and other agents. In the lab, researchers use electroporation to introduce genes, drugs, and other compounds into cells and experimental animals. This is a common and well-known procedure and more than 4,000 scientific papers have been published describing results achieved using electroporation.
• While widely used in the research arena, electroporation is a relatively new technology in the therapeutic arena. One of the major difficulties in many forms of drug or gene therapy is that the pharmaceutical agent or gene is often not able to penetrate the relatively impermeable walls of cells. The pores produced by electroporation permit entry of such agents into cells to a much greater extent than if the drug or gene was administered without electroporation. When electroporation is used in conjunction with drugs, genes, or other therapeutic agents, it is referred to as Electroporation Therapy (“EPT”). We operate through our two divisions: (i) the Drug and Gene Delivery Division, through which we are developing drug and gene delivery systems based on electroporation to be used in the treatment of disease and, (ii) the BTX Instrument Division, which develops, manufactures, and sells electroporation equipment to the research laboratory market for in vitro and for in vivo animal experimentation.
• The Drug and Gene Delivery Division focuses on the development of human-use equipment that is designed to allow physicians to use EPT to achieve more efficient and cost-effective delivery of drugs or genes to patients with a variety of illnesses, including cancer. Our proprietary electroporation drug and gene delivery system, the Genetronics MedPulser® system, has been used with bleomycin, a chemotherapeutic agent, in clinical trials conducted in the United States, Australia, Europe and Canada for treatment of head and neck cancer, as well as melanoma, liver, pancreatic, basal cell and Kaposi sarcoma cancers.

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• OVERVIEW
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• Through our Drug and Gene Delivery Division, we are developing drug and gene delivery systems based on the technology of electroporation to be used in combination with drugs or genes in the treatment of disease. There are many diseases where improved drug delivery is important. Our Drug and Gene Delivery Division has identified five potential areas of application for our electroporation technology — oncology, gene therapy, dermatology, cardiology and transdermal drug delivery. At present, the primary areas of our focus are oncology and gene therapy.
• Our Drug and Gene Delivery Division’s most advanced product candidates treat solid malignant tumors such as squamous cell carcinoma, melanoma, and adenocarcinoma in the areas of application of oncology and dermatology. We have completed Phase II clinical trials in the United States of EPT and bleomycin in the treatment of head and neck cancer and melanoma. Initial results from the clinical trials carried out in Europe have allowed us to obtain a CE Mark certification qualifying the MedPulser® system for sale in Europe with respect to the treatment of head and neck cancer and melanoma using EPT and bleomycin. We intend to initiate the marketing of the MedPulser® System in Europe in 2001.
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• We intend to develop and pursue other appropriate targets using the MedPulser® System to deliver bleomycin or other chemotherapeutic agents. Such studies will begin as Phase I or Phase II clinical trials. Phase I clinical trials are early stage trials in human subjects, used to test a drug or delivery system for safety. Phase II clinical trials assess the effectiveness of a treatment, as well as adding to safety data. Phase III clinical trials evaluate the comparative safety and efficacy of a drug or delivery system and the data from these trials are used by regulatory agencies to approve or reject a product licensing application.
• Our drug delivery system, including the MedPulser® instrument and the disposable applicators, are subject to various regulatory requirements depending on the country of sale. The Drug and Gene Delivery Division MedPulser® system has been awarded ISO 9001, EN46001 and ISO 13485 registration, as well as CE mark certification in Europe.
• MARKET
• Our Drug and Gene Delivery Division is expected to enter the commercial market with equipment to be used in the treatment of cancer (oncology). Cancer is a life threatening disease affecting millions of people worldwide. The World Health Organization reports that cancer will remain one of the leading causes of death worldwide for years to come. In the United States, approximately 13 million new cases were diagnosed between 1990 and 1999. To further illustrate the market potential for EPT, solid tumor cancers, the first target for EPT, constitute the majority of all cancers. The majority of cancer victims are over age 65 and are supported by government-funded programs. In the United States the costs of cancer, including mortality, morbidity and direct medical costs, exceed $107 billion per year: some $37 billion for direct medical costs (total of all health expenditures); at least $11 billion for indirect morbidity costs (cost of lost productivity due to illness); and over $59 billion for indirect mortality costs.
• There is still very much that scientists do not know about cancer; consequently, there are significant unmet needs in the treatment of cancer. The oncology business unit within the Drug and Gene Delivery Division has initially targeted those indications for which current treatment modalities result in a poor quality of life and very high mortality rates. Specialized applicators are being designed which will allow EPT to treat other solid tumor cancers with minimally invasive procedures.
• In the United States, the cumulative dollar value of treatments and technologies commonly used in the curative and palliative management of cancer exceeded $8 billion in 1999 and is expected to continue growing at a rate of approximately 12% annually. Our analyses project that EPT could be applicable to over 4,000,000 cancer patients. This analysis is based upon the reported incidence of head and neck cancers throughout the world as reflected by statistics obtained from the American Cancer Society, the World Health Organization and the National Institutes of Health.
• TREATMENT OF TUMORS
• Equipment made by our BTX Instrument Division has been used by our investigators and in other laboratories to screen drugs for their effectiveness in killing tumor cells in test tubes and to study the drugs’ mode of action. Our scientists, and outside researchers, also have studied the combination of electroporation and various agents to destroy tumors in animals and humans.
• In most of the clinical protocols, the site of the tumor is anesthetized and the chemotherapeutic agent of choice (bleomycin) is injected directly into the tumor. The therapeutic agent is allowed to diffuse throughout the tumor, which can take one to several minutes depending on the size, type and location of the tumor. Once the drug is distributed in the tumor, the electrical field is applied by the MedPulser® system so as to create a greater permeability in the cells walls to allow the chemotherapeutic agent to enter the cells.
• The entire procedure can be completed in 20 minutes or less and typically needs to be done only once. The dosage of drug used in the published results is based on tumor volume, and is typically a small fraction (1/3 to as little as 1/50) of the dosage that would be used systemically. As a result of the lower dosage administered locally, side effects have been minimal. Tumor death with sloughing and ulceration were common reactions following EPT. No episodes of injury to normal (non-tumor) tissue adjacent to the tumors have been observed.
• MEDPULSER® SYSTEM
• The MedPulser® system is an electroporation system designed for the clinical application of EPT. The technology is intended to treat various malignant and non-malignant tumors by locally applying a controlled electric field to targeted tumor tissues previously injected with a chemotherapeutic agent. The controlled short duration electric field pulses temporarily increase the cellular membrane permeability of the tumor cell membrane allowing the therapeutic agent to more easily enter the tumor cells and kill them.
• The system has two components: (1) a medical instrument which creates the electric field (the MedPulser® instrument); and (2) a single use, sterile, disposable electrode applicator. The electrodes may be needles, plates, or other configurations, depending on the geometry of the tumor and its location.
• The instrument was designed for ease of use, such that minimal user input is needed to apply the therapy. Based on the size and anatomical location of the tumor to be treated, a physician selects the most appropriate electrode applicator. The chosen applicator is then connected to the MedPulser® instrument,
• and it is the connection of applicator to instrument that automatically configures the therapy parameters for that particular applicator size and shape. Currently, several different electrode applicator configurations are available. The applicators vary in needle length, needle gauge, electrode needle spacing, tip angle and handle configuration so as to allow the physician to access a greater range of tumors.
• New models of electrode applicators will be considered in the future to address customer needs. The system is designed such that the installed base of MedPulser® generator instruments allows for a wide variety of new electrode applicator configurations. Also, the system incorporates other features to minimize the possibility of applicator reuse as well as prevent the use of competitive applicators with the MedPulser® instrument. The commercial version MedPulser® system has been certified by an independent test laboratory as meeting strict international product standards. Our drug delivery device, including the MedPulser® system and the disposable electrode applicators, are subject to various regulatory requirements, depending on the country of sale.
• In the United States, EPT utilizing the MedPulser® system and bleomycin drug is currently regulated as a combination drug-device system. We will be required to obtain both drug labelling and device approvals from the United States Food and Drug Administration (“FDA”). Clinical trials (Phase I, II and III) to support drug indication labelling require filing an Investigational New Drug Application (“IND”), followed by submission of a United States New Drug Application, and submission of a device Pre-Market Approval or 510(k), for marketing approval.
• In most of the rest of the world, we anticipate that the MedPulser® system will be regulated as a device. In Europe, the device comes under the Medical Device Directive 93/42/EEC (“MDD”) and marketing requires CE mark certification of conformity to the quality system, production and clinical investigation essential requirements of the directive. We have obtained CE mark certification for electroporation devices, which allows us to sell and use the MedPulser® electroporation system for the treatment of solid tumors with bleomycin in Europe.
• MEDICAL DEVICE MANUFACTURING
• Our Drug and Gene Delivery Division must comply with a variety of regulations to manufacture our products for sale around the world. In Europe, we must comply with MDD. Our Drug and Gene Delivery Division has demonstrated the quality system is in place by securing ISO 9001 approval. It demonstrated compliance with international medical device standards with EN 46001 and ISO 13485 recognition. These all occurred in January 1999. In March 1999, the CE Mark was obtained for the MedPulser® electroporation system. To sell in the United States, we will need to be in compliance with FDA current Good Manufacturing Practices (GMP).
• We employ modern manufacturing practices, which include outsourcing of significant custom assemblies used in the manufacture of the MedPulser® instrument. The instrument final assembly, testing and quality control functions are performed in a physically distinct area of the company where the appropriate controls are employed. We outsource the manufacture of the disposable electrode applicators to a GMP/ISO9002 compliant contract manufacturer.
• CLINICAL STUDIES
• North America Trials
• In late 1997 the FDA gave us clearance to initiate multi-center Phase II clinical trials in the United States utilizing the MedPulser® electroporation system in combination with intralesional bleomycin to treat squamous cell carcinoma of the head and neck in patients who failed conventional therapies. We obtained IND clearance from the Canadian Health Protection Branch to initiate similar clinical trials in Canada. Two protocols were initiated. One cross-over-controlled study evaluated the effectiveness of the bleomycin-EPT treatment in tumors that failed an initial bleomycin-alone treatment. The second study was a single arm study that evaluated the effect of the bleomycin-EPT treatment as an initial therapy of the study tumors.
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• International Trials
• In late 1997 and early 1998, we received ethics committee approval from multiple Consulting Committees for the Protection of Humans in Biomedical Research (CCPPRB) to initiate clinical trials in France in patients with pancreatic cancer, metastatic cancer in the liver, head and neck cancer, melanoma and Kaposi’s sarcoma. There were a total of 46 patients enrolled in these trials. CCPPRB provides oversight of proposed and actual human clinical trials to protect the participants in these trials and ensure that safety standards are met. These trials were initiated to demonstrate the MedPulser® system device’s safety and performance in treating a variety of solid tumors in support of CE mark certification in accordance with the essential requirements of the Medical Device Directive (MDD). Results from those patients in this trial with head and neck cancer are reported under North America Trials above. We achieved CE mark certification in March 1999 from notified body TUV Product Service GMBH (TUV). TUV oversees and audits clinical trials, reviews the results of the these trials and certifies compliance with established European standards. The CE mark certification allows us to market our MedPulser® device within the EU member countries.
• Current Developments
• On October 6, 1998, we entered into a comprehensive License and Development Agreement and a Supply Agreement with Ethicon, Inc., a Johnson & Johnson company, involving our proprietary drug delivery system for EPT treatment of cancer. In August 5, 1999, these agreements were assigned to Ethicon Endo-Surgery, Inc., another Johnson & Johnson company. Ethicon, Inc. and Ethicon Endo-Surgery, Inc. are referred to as Ethicon in this filing. On July 26, 2000, we received written notice from Ethicon Endo-Surgery, Inc. that it had elected to exercise its discretionary right to terminate, without cause, the License and Development Agreement and the Supply Agreement. All rights for the development and distribution of Genetronics proprietary electroporation drug delivery system for the treatment of cancer were returned to Genetronics on termination of the agreement on January 2001.
• In September 2000, we executed an exclusive license agreement with the University of South Florida Research Foundation, Inc. (“USF”) that granted to us the worldwide license to USF’s rights in certain patents and patent applications generally related to needle electrodes. Genetronics and USF jointly developed these electrodes. The needle electrodes are components of Genetronics’ electroporations systems and are used to deliver electric pulses to cells and tissues during the process of electroporation. Pulsed electric fields generated during the electroporation process cause a temporary but significant increase in the permeability of human cells. This makes it easier for drugs and genes to enter cells, a key element for successful cancer or gene therapy treatment. In April 2001, we initiated a limited release of the MedPulser® Electroporation Therapy System, to key head and neck surgeons in several countries through a European Access Program (EAP). We have initiated a marketing evaluation of the technology, under the EAP, with a select group of thought leaders at premier cancer centers in Austria, the United Kingdom, Germany, the Netherlands, Switzerland, and the Czech Republic. Genetronics has a CE Mark certification qualifying the MedPulser® system for sale in Europe for the treatment of solid tumors. The lead indication for the planned launch of the MedPulser® Electroporation Therapy System is the treatment of head and neck cancers and the initiation of the EAP represents the beginning of the commercialization phase of our EPT program for head and neck cancer in Europe. We believe we have sufficient current resources to initiate a variety of activities directed toward the MedPulser® system launch and marketing in Europe, and for initiation of a Phase III clinical study in the United States. In April 2001, we completed a review of our existing clinical and regulatory information related to the Electroporation Drug Delivery System and submitted the results of this review to the FDA. The responses are described above under “Clinical Studies—North America Trials.” The response rate determined pursuant to the review is consistent with previous data disclosed by us.
• Research and Development Summary
• We perform an ongoing review of our patent portfolio to confirm that our technologies are adequately protected. Each year we review our patent portfolio and write-off all abandoned patents.
• Our Drug and Gene Delivery Division has, in the past, focused its research primarily in the areas of oncology, gene therapy, vascular therapy, transdermal delivery and dermatology. At present, the primary areas of focus are oncology and gene therapy.
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• GENE THERAPY
• Gene therapy, in classical terms, involves the introduction of new genetic information into cells (transfection) for therapeutic purposes. Somatic cells of the body are transfected with a specific functioning gene to compensate for a genetic defect that results in a deficiency of a specific protein factor. In this context, one goal of gene therapy is to convert target cells or tissues into “protein factories” for the production and secretion of a normal protein locally or into the circulation. Many vexing genetic illnesses, including those currently treated by regular injection of a missing protein, can potentially be “cured” by supplying the functional gene to a sufficient number of cells under conditions which allow these cells to produce a therapeutically effective dose of the gene product.
• Currently, single-gene recessive genetic disorders are the most accessible targets for correction by gene therapy, but ultimately polygenic and acquired diseases can and will be treated by using genes as pharmaceutical agents. In principle, any aspect of metabolism can be manipulated by modifying gene function, and it is this application of gene therapy that has enormous potential, extending far beyond the treatment of rare genetic diseases. For example, the ability to influence cellular metabolism by introducing specific genes has led to extensive investigation into the use of gene therapy for cancer treatment. By adding a tumor suppressor gene to certain types of cancers, the uncontrolled growth of those cells potentially could be brought under normal regulation. Likewise, transfecting tumor cells with genes capable of inducing programmed cell death can result in tumor ablation.
• The methods of introducing genes have two specific approaches. Gene therapy can be performed either ex vivo or in vivo. Ex vivo gene therapy is the transfection of cells outside the body. Typically, a small amount of tissue is removed from the patient and the cells within that tissue are put into culture. The genetically modified cells, typically blood, bone marrow or others, are then returned to the patient, usually by blood transfusion or direct engraftment. In vivo gene therapy is the introduction of genetic information directly into cells in the patient’s body. Theoretically, any tissue or cell type in the body can be used, and the choice is dependent on the specific goals of treatment and indications being treated. For internal tissue targets, a gene may be transfused through the blood stream to the organ or site of action, or it may be injected at the desired site, which is then electroporated to allow the gene to pass through the cell membrane.
• Genes can also be applied topically or by injection to skin and then transferred into the cells of the skin by electroporation. Skin gene delivery by electroporation for gene therapy is currently being investigated at Genetronics as a safe, effective and cost-competitive approach. The skin is also a target for DNA vaccination. “Vaccinating” skin with DNA that encodes a specific antigen present in infectious agents or in tumor cells can produce beneficial immunological responses. Genes can also be used to directly fight cancer. The thymidine kinase gene, in conjunction with the prodrug ganciclovir, produces a potent antitumor effect based on drug toxicity and programmed cell killing via a bystander effect. Animal trials treating glioblastomas using this strategy have shown substantial success.
• To make gene therapy a reality, many obstacles have to be overcome, including the safe, efficient delivery of the intact DNA construct into the host cells. The instrumentation we use for high-efficiency in vivo gene transfer is derived from the instrumentation developed for intratumoral and transdermal drug delivery. We believe electroporation will become the method of choice for DNA delivery to cells in many applications of gene therapy.
• Because of the broad applicability of this technology, we have adopted the strategy of co-developing or licensing our technology exclusively or non-exclusively for specific genes or specific medical indications. In most cases, we contribute proprietary technology, expertise and instrumentation to optimize the delivery technology for particular applications. A partner company provides its proprietary DNA constructs, may conduct the pre-clinical research and clinical trials, and may introduce the new treatment and products to the marketplace. Genetronics and the partner company would share in the commercial success of the project. We have actively sought partners to develop this exciting technology to its full potential. On November 8, 1999, we entered into an 18-month research and option agreement with Boehringer Ingelheim International GmbH (Boehringer Ingelheim) related to the development of our electroporation technology for use in particular gene therapy applications. While the research results were successful Boehringer Ingelheim decided not to pursue that subject field and declined to exercise the option to license. On June 9, 2000, we announced that research studies using our electroporation systems were presented at a major international gene therapy conference. Additionally, in collaborations with Chiron Corporation and Valentis, Inc., our technology was shown to effectively deliver a variety of genes and DNA vaccines to skin and muscle of animals, including non-human primates.
• BTX INSTRUMENT DIVISION
• OVERVIEW
• Our company, through our BTX Instrument Division, began developing and manufacturing electroporation equipment for the research laboratory market in 1983 and sold our first product in 1985. BTX was founded to develop and manufacture high quality scientific instrumentation that can be used by research scientists to perform various types of electroporation and electrofusion experiments. Electroporation in research is commonly used for transformation and transfection of all cell types, as well as for general molecular delivery at the cellular level. Electrofusion is the fusing together of two or more cells to form hybrid cells. Transformation is a process by which the genetic material carried by an individual cell is altered by incorporation of exogenous DNA into its genome. Transfection is the uptake, incorporation, and expression of exogenous DNA by eukaryotic cells.
• The BTX Instrument Division is the second largest developer and marketer of electroporation instruments and supplies, with more than 2,000 customers in universities, companies, and research institutions worldwide. Our BTX Instrument Division sells its electroporation/electro cell fusion instrumentation and accessories to customers located in all states and territories of the United States and in over 47 foreign countries. The majority of our products are sold to customers in the United States, Europe and East Asia. The BTX Instrument Division currently produces an extensive line of electroporation instruments and accessories, including electroporation and electro cell fusion instruments, a monitoring device, and an assortment of electrodes and accessories.
• PRODUCTS
• BTX developed the square wave generator and graphic pulse analyzer for in vivo gene delivery and nuclear transfer research, fields that are rapidly increasing in scientific and medical interest. BTX also has developed a large volume flow-through electroporation system which offers an extensive collection of in situ and high throughput screening electroporation applicators.
• BTX focused its efforts in recent years on product development and promotion of a new line of products for developing sophisticated applications. We released the ECM™ 830 in December 1998. It is a sophisticated square wave electroporation system with a menu driven digital user interface. In August 1999 we introduced the ECM 630, an Exponential Decay Wave Electroporation system that utilizes a Precision Pulse Technology, the new BTX Platform technology, and an all-new digital user interface. During the fiscal years ended March 31, 2001 and 2000, publications outlined the utilization of BTX equipment in newly developing animal in vivo gene delivery research. In the support of this research, we expanded our in vivo electrode offering and continue to emphasize the development of novel applicators.
• The BTX Instrument Division’s product line includes two exponential decay wave generators, one square wave generator, one electro cell fusion instrument and a graphic wave display monitor. In addition, this Division markets over 43 different types of electrodes and related accessories, as well as the standard disposable electroporation cuvettes, containers for holding liquid samples.
• Exponential decay generators have been traditionally used for the electroporation of all cell types. Square wave generators have shown the greatest utility in the electroporation of mammalian and plant cells, as well as for animal in vivo applications. The Electro Cell Fusion System is used by researchers for embryo manipulation, hybridoma and quadroma formation, as well as for all cell fusion techniques, including applications involving adoptive immunotherapy.
• While we, through our BTX Instrument Division, sell devices purportedly used by others for non-human embryo cloning, we do not ourself conduct embryo cloning. All of our BTX Instrument Division instruments sold to the research market carry the label “not for human use.” We are not aware of any regulations or industry guidelines limiting the use of our instrumentation in the animal research market. We comply with all National Institutes of Health guidelines on cloning and gene therapy. We also comply with all Federal and State regulations regarding the restrictions on research imposed on federally funded grants.
• The BTX Instrument Division supplies three cuvette models, as do our competitors, plus some 43 additional specialized chambers electrodes, and accessories for electroporation. BTX in situ electrodes (e.g., Petri Pulser™ electrodes) position us to expand the electroporation market for adherent cell transfection applications, while high throughput screening electrodes and large volume production systems (e.g., 96-Well Coaxial Electrode, ElectroFlowPorator™ system), respectively, provide the BTX Instrument Division with an entry into the large volume and multi-sample processing arenas used by the major pharmaceutical and biotech companies conducting drug research.
• The BTX Instrument Division meets regulatory requirements necessary to provide instrumentation to the research market for in vivo and in vitro animal experimentation. The BTX Instrument Division does not market equipment for use in humans, and, therefore, is not required to receive marketing approval from the FDA.
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• COMPETITION
• The main competitors of our BTX Instrument Division in the research marketplace are BioRad Laboratories, Eppendorf Scientific, Inc. and Hybaid Corporation. There are other companies entering and departing this market on a regular basis. The majority of these companies have other molecular biology product lines besides electroporation, while electroporation and electrofusion is the only business of the BTX Instrument Division. Most competing manufacturers concentrate on the exponential decay wave system and do not compete in the square wave market at this time. In the past 12 months, the competition in the marketing of electroporation cuvettes has increased, leading to the development of BTX-supplied private label products for both VWR and Fisher Scientific.
• STRATEGIC PARTNERS
• LICENSE AND DEVELOPMENT AGREEMENTS
• On October 6, 1998, we entered into a comprehensive License and Development Agreement and a Supply Agreement with Ethicon, Inc., a Johnson & Johnson company, involving the use of our MedPulser® system for Electroporation Therapy in the treatment of solid tumor cancer. In addition, Johnson & Johnson Development Corporation purchased $6 million of shares of common stock of our company at a price of $2.68 per share, pursuant to the October 6, 1998 Stock Purchase Agreement. On August 5, 1999, we announced that Ethicon, Inc. had assigned the License and Development Agreement and Supply Agreement to Ethicon Endo-Surgery, Inc., another Johnson & Johnson company. On July 26, 2000, we received written notice from Ethicon Endo-Surgery, Inc. that it had elected to exercise its discretionary right to terminate, without cause, the License and Development Agreement and the Supply Agreement. As a result, all rights for the development and distribution of Genetronics proprietary electroporation drug delivery system for the treatment of cancer were returned to Genetronics in January 2001.
• On September 20, 2000, the University of South Florida Research Foundation, Inc. (“USF”) granted to Genetronics, Inc. and Genetronics Biomedical Ltd. an exclusive, worldwide license to its rights in certain patents and patent applications generally related to needle electrodes. Genetronics and USF jointly developed these electrodes. The needle electrodes are components of Genetronics electroporation systems and are used to deliver electric pulses to cells and tissues during the process of electroporation. Pulsed electric fields generated during the electroporation process cause a temporary but significant increase in the permeability of human cells. This makes it easier for drugs and genes to enter cells, a key element for successful cancer or gene therapy treatment. The terms of the exclusive license include a royalty to be paid to USF based on net sales or products under the license. At March 31, 2001, no royalty had accrued as the Company had not yet generated any sales from this product. In addition, Genetronics has issued a total of 150,000 common shares and a total of 600,000 warrants of which 300,000 will vest subject to the achievement of certain milestones in Genetronics Biomedical Ltd. to USF and its designees, Drs. Heller, Jaroszeski, and Gilbert.
• COLLABORATIVE RESEARCH AGREEMENTS
• On November 8, 1999, we entered into an 18-month research and option agreement with Boehringer Ingelheim to develop our electroporation technology for use in a particular gene therapy application. Under the terms of the agreement, we will develop hardware and perform preclinical research relating to DNA delivery for cancer DNA vaccination. While the research results were successful Boehringer Ingelheim decided not to pursue that subject field and declined to exercise the option to license. On August 28, 2000, we announced that we had entered into a collaborative agreement with Johnson & Johnson Research Pty Ltd., a wholly owned subsidiary of Johnson & Johnson, located in Eveleigh, Australia, to explore the feasibility of using electroporation, Genetronics platform technology, to deliver nucleic acid materials into tumors in vivo.
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Genetronics Biomedical Corporation has been granted two new U.S. patents covering different aspects of its electroporation technology for medical applications. In the first patent, U.S. Patent Number 6,569,149, entitled, "Method of Treatment Using Electroporation Mediated Delivery of Drugs and Genes," the company has been allowed claims to methods for applying electric fields to patient tissue afflicted with a cell proliferation disorder, using the company's proprietary and patented field generating methodologies, particularly the use of multiple opposed pairs of electrodes.

In the second patent, U.S. Patent Number 6,567,694, entitled, "Needle Electrodes for Mediated Delivery of Drugs and Genes," claims were granted for an electrode apparatus for the application of electric fields wherein electrodes are positioned within a hollow needle. The Company believes this electrode configuration may be useful in the delivery of gene therapeutics and DNA vaccines.

Avtar Dhillon, Genetronics' President and CEO, said, "The claims of the two new patents cover differing electrode formats for performing electroporation in cancerous tissues and in micro-environments, respectively. The new patents are an important part of Genetronics' ongoing strategy to maintain its commercial position in developing medical applications of electroporation."

SAN DIEGO and OSLO, Norway, Jan. 26 /PRNewswire-FirstCall/ -- [ Genetronics Biomedical Corporation]. , a late stage developer of oncology and other therapies using electroporation to deliver drugs and nucleic acids, announced today the acquisition of Oslo-based [Inovio AS ], a leader in patented gene delivery technology for the most efficient, nonviral method for gene transfer to skeletal muscles. Inovio's use of electroporation for gene therapy and DNA vaccines is a complement to Genetronics' existing electroporation therapy program. The acquisition expands Genetronics' intellectual property in electroporation, expands the number of agreements with major pharmaceutical companies, and provides for the near-term initiation of a Phase I/II DNA vaccine clinical trial.

The deal includes cash in Inovio's treasury of approximately $775,000 and approximately $2.0M in current and anticipated appropriations for biodefense research from the US Army and other committed grants. The share purchase agreement consists of $3M in cash, $7M in Genetronics stock, and potential additional share payments given the achievement of certain revenue milestones. In addition, Iacob Mathiesen, Ph.D., Inovio's CEO, will serve as Executive Director, Gene Delivery of Genetronics.

"This is a perfect strategic fit as we increase our licensing activities in the area of DNA therapies involving intramuscular electroporation for application to vaccines and immunotherapy," said  [Dr. Avtar Singh Dhillon (born 1961)], Genetronics' President and CEO. "Together with Dr. Mathiesen and his team, we will promote and advance gene-based collaborations with existing and new partners. We anticipate that license revenue from our DNA delivery technology will be increasingly important in creating additional value for our shareholders."

"I am delighted to bring our technology and products to [ Genetronics Biomedical Corporation], the market leader in electroporation-based therapies," noted Iacob Mathiesen, Ph.D., [the CEO of Inovio AS]. "Genetronics is in an enviable position to enable the advancement of DNA vaccinations and gene therapy, and I am certain that the company will play a prominent role in this promising and rapidly growing area."

• About [ Genetronics Biomedical Corporation] :    Genetronics Biomedical Corporation is a late stage biomedical company focused on building an oncology franchise based on its proprietary electroporation therapy. The therapy targets a significant unmet clinical need: the selective killing of cancer cells and local ablation of solid tumors while preserving healthy tissue. The company is moving its lead product, the MedPulser(R) Electroporation Therapy System, through pre-marketing studies for head and neck cancer and skin cancer in Europe, where it has CE Mark accreditation, and a Phase III pivotal study for recurrent head and neck cancer in the U.S. Merck, Vical, Chiron, the US Navy, and other partners are employing Genetronics' electroporation technology, which enhances local delivery and cellular uptake of a number of biopharmaceuticals, in their development of novel DNA vaccines and gene therapies. Genetronics is a leader in electroporation, with over 240 patents worldwide that are issued, allowed or pending. More information can be obtained at http://www.genetronics.com/.

SAN DIEGO, CA., September 13, 2004 — Genetronics Biomedical Corporation (AMEX: GEB), a late stage developer of cancer and other therapies using electroporation-enabled delivery of drugs, DNA vaccines, and genes, announced today that the company’s board of directors has approved a 1-for-4 reverse stock split of its shares. The common stock will begin trading on a reverse split basis on the American Stock Exchange as of the opening of trading today, Monday, September 13, 2004. There is no symbol change.

Total shares voted, 56,578,878, was equal to 66.2% of total voteable shares (voteable shares include common shares plus common-share-equivalent voting rights attached to outstanding preferred shares). Shares voted in favor of the reverse split amounted to 49,201,399, or 87% of votes cast.

“Our company’s shareholders clearly indicated their strong support for the proposed reverse split, and the board of directors and management moved decisively to implement this resolution,” said Avtar Dhillon, MD, President & CEO. “We believe we are in a solid position to continue to execute on the fundamentals that will allow us to advance our electroporation therapy towards commercialization, which is expected to begin in 2005 in Europe.”

About Genetronics Biomedical Corporation

Genetronics Biomedical Corporation is a late stage biomedical company focused on building an oncology franchise based on its proprietary electroporation therapy. The therapy targets a significant unmet clinical need: the selective killing of cancer cells and local ablation of solid tumors while preserving healthy tissue. The company is moving its lead product, the MedPulser® Electroporation Therapy System, through pre-marketing studies for head and neck cancer in Europe, where it has CE Mark accreditation, and a U.S. Phase III pivotal study for recurrent head and neck cancer. Merck, Chiron, the US Navy, Vical and other partners are also employing Genetronics’ electroporation technology, which enhances local delivery of drugs and DNA, in their developments of novel DNA vaccines and gene therapies. Genetronics is a leader in electroporation, with over 240 patents worldwide that are issued, allowed or pending. More information can be obtained at www.genetronics.com.

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This press release contains certain forward-looking statements relating to Genetronics’ plans to develop its electroporation drug and gene delivery technology and to maximize shareholder value. Actual events or results may differ from Genetronics’ expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs, evaluation of potential opportunities, the level of corporate expenditures, the assessment of Genetronics’ technology by potential corporate partners, and capital market conditions, and others set forth in the Genetronics Annual Report, on Form 10-K for the 12-month period ending December 31, 2003, and the Form 10-Q for the 3-month period ending March 31, 2004, and other regulatory filings. There can be no assurance that any product in the Genetronics product pipeline will be successfully developed or manufactured, or that final results of human pilot studies or clinical studies will be supportive of regulatory approvals required to market Licensed Products. The American Stock Exchange has not reviewed and do not accept responsibility for the adequacy or accuracy of this release