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.

SAN DIEGO--(BUSINESS WIRE)--Jun. 24, 2009-- [Inovio Pharmaceuticals, Incorporated  - known at this time as "Inovio Biomedical Corporation" ]  (NYSE Amex: INO), a leader in DNA vaccine design, development and delivery, announced today that [Dr. Stanley Alan Plotkin (born 1932)] has agreed to join the company’s scientific advisory board.

[Dr. Stanley Alan Plotkin (born 1932)] developed the rubella vaccine now used worldwide and has worked extensively on the development and application of other vaccines including polio, rabies, varicella, rotavirus and cytomegalovirus. He is Emeritus Professor, Wistar Institute and the University of Pennsylvania, and Executive Advisor to the CEO of Sanofi Pasteur.

Over the course of his career [Dr. Stanley Alan Plotkin (born 1932)] has served as senior assistant surgeon with the Epidemic Intelligence Service, U.S. Public Health Service; director of the Division of Infectious Diseases at Children’s Hospital ofPhiladelphia; associate chairman of the Department of Pediatrics, University of Pennsylvania; and medical and scientific director of Aventis Pasteur.

Dr. Plotkin’s professional awards include the Sabin Foundation Medal (2002); the French Legion Medal of Honor (1998); the Clinical Virology Award, Pan American Group for Rapid Viral Diagnosis (1995); the Distinguished Physician Award, Pediatric Infectious Disease Society (1993); and the Bruce Medal of the American College of Physicians (1987).

[Dr. Jong Joseph Kim (born 1969)] , Inovio’s CEO, stated, “[Dr. Stanley Alan Plotkin (born 1932)] is an internationally renowned virologist who has made significant contributions to the goal of conquering diseases with vaccines. We are honored to have Dr Plotkin join our distinguished panel of scientific advisors, who are committed to helping guide Inovio’s development of DNA vaccines, a potentially vital new generation of vaccines targeting cancers and chronic infectious diseases.”

[Dr. Stanley Alan Plotkin (born 1932)] joins [Dr. David B. Weiner (born 1955)] and [Robert Samuel Langer Jr. (born 1948)]  on Inovio's Scientific Advisory Board. Dr. Weiner is Chairman of the Scientific Advisory Board and is a professor of the Department of Pathology & Laboratory Medicine, University of Pennsylvania. Dr. Weiner is considered to be a pioneer of the field of DNA vaccines. Dr. Langer, Germeshausen Professor of Chemical and Biomedical Engineering at theMassachusetts Institute of Technology, is a renowned scientist with numerous distinguished awards. Drs. Weiner and Langer have both advised organizations such as the FDA and multiple life sciences companies. Both Drs. Weiner and Langer have served as founding members of the scientific advisory board of VGX Pharmaceuticals, which merged with Inovio Biomedical on June 1, 2009.

• About Inovio Biomedical Corporation :   Inovio Biomedical is engaged in the design, development, and delivery of a new generation of vaccines, called DNA vaccines, focused on cancers and infectious diseases. The company’s SynCon™ technology enables the design of DNA-based vaccines capable of providing cross-protection against evolving, unmatched strains of pathogens such as influenza. Inovio’s proprietary electroporation DNA delivery technology uses brief, controlled electrical pulses to increase cellular DNA vaccine uptake. Initial human data has shown this method can safely and significantly increase gene expression and immune responses. Inovio’s clinical programs include HPV/cervical cancer (therapeutic) and HIV vaccines. An IND has been filed for an avian influenza vaccine. Partners and collaborators include Merck, Tripep, University of Southampton, University of Pennsylvania, and HIV Vaccines Trial Network. Inovio’s product candidates and technologies are protected by an extensive global intellectual property portfolio. More information is available at www.inovio.com.

SAN DIEGO, Dec 21, 2009 (BUSINESS WIRE) -- Inovio Biomedical Corporation (NYSE Amex:INO), a leader in DNA vaccine design, development and delivery, announced today that it has appointed Iacob Mathiesen, Ph.D., to its Scientific Advisory Board. Dr. Mathiesen is an international expert in the field of electroporation delivery of biopharmaceuticals including DNA vaccines.

Dr. Mathiesen was previously managing director of Inovio's Norwegian subsidiary, Inovio AS. He received a B.Sc. in Mathematics and Natural Sciences in 1991, an M.Sc. in Mathematics and Natural Sciences in 1993, and a Dr.Philos. in Neurobiology in 1999, all from the University of Oslo, Norway. He is the co-inventor of multiple patents and co-authored numerous scientific papers pertaining to the use of electroporation as a mechanism to safely and significantly enhance the cellular uptake of biological materials and, in the case of DNA-based vaccines, resulting levels of gene expression. His first patent application was the first public disclosure of the use of electroporation to deliver DNA and gene based vaccines to skeletal muscles.

Dr. Mathiesen joins an eminent group of scientific advisors who have and continue to play prominent roles in advancing the fields of vaccines, DNA vaccines and drug delivery, including: 

1. [Dr. David B. Weiner (born 1955)]. :   Professor, Dept. of Pathology & Laboratory Medicine, University of Pennsylvania Chairman, Scientific Advisory Board, Inovio Biomedical

2. [Robert Samuel Langer Jr. (born 1948)] :   Professor, Chemical and Biomedical Engineering, Massachusetts Institute of Technology

3. [Dr. Stanley Alan Plotkin (born 1932)]. :   Emeritus Professor, Wistar Institute and University of Pennsylvania Consultant, Sanofi Pasteur

[Dr. Jong Joseph Kim (born 1969)], President and CEO, Inovio Biomedical, stated, "Dr. Mathiesen has pioneered important advancements in the methods, conditions, and devices that are resulting in electroporation becoming one of the most promising - if not the most promising - methods of delivering DNA vaccines. His scientific acumen and leadership will be invaluable as Inovio continues to advance toward its goal of enabling the capabilities of this important new generation of vaccines."

• About Inovio Biomedical Corporation :   Inovio Biomedical is focused on the design, development, and delivery of a new generation of vaccines, called DNA vaccines, to prevent and treat cancers and infectious diseases. The company's SynCon(TM) technology enables the design of "universal" vaccines capable of protecting against multiple - including newly emergent, unknown - strains of pathogens such as influenza. Inovio's proprietary electroporation-based DNA vaccine delivery technology has been shown by initial human data to safely and significantly increase gene expression and immune responses. Inovio's clinical programs include HPV/cervical cancer (therapeutic) and HIV vaccines. An IND has been filed for an avian influenza vaccine. Inovio is developing its universal and avian influenza vaccines in collaboration with scientists from the University of Pennsylvania, the National Microbiology Laboratory of the Public Health Agency of Canada, and the NIH's Vaccine Research Center. Other partners and collaborators include Merck, Tripep, University of Southampton, National Cancer Institute, and HIV Vaccines Trial Network. More information is available at http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.inovio.com&esheet=6124916&lan=en_US&anchor=www.inovio.com&index=4&md5=2fa327dc9786ae499f5970ad62eaf1d0.

[...]

Analysis of VGX International Co., Ltd.

1. 1. The reporting entity, its related parties, or both participated significantly in the design or redesign of the legal entity
   1. • Neither Inovio nor VGXP participated significantly in the design or redesign of VGX Int’l. As mentioned above, VGX International (“VGX Int’l”) has been publicly-traded and listed on the Korean Stock Exchange since November 1987.
      • VGX Int’l is a Korea-based company engaged in the manufacturing of woven and knitted interlinings, as well as the production of pharmaceuticals. VGX Int’l’s interlinings have applications in dress shirts, shirts, blouses and caps, which are provided under the brand name of INTERON. Inovio distributes its interlining products, which are produced by its factory in Vietnam, to apparel companies in domestic and international markets. VGX Int’l is also involved in the development of new drugs and the contract manufacturing organization (CMO) business, providing diabetes remedies, influenza deoxyribonucleic acid (DNA) vaccines and remedies for stomach cancer.
      • VGX Int’l currently generates two-thirds of its total revenue from its fabric manufacturing business. VGX Int’l’s other business units are dedicated to contract manufacturing high-end biopharmaceutical products to global clients, currently through its subsidiary VGXI, Inc., and developing new drug candidates for the treatment of infectious and inflammatory diseases. VGX Int’l’s clinical development programs include VGX-1027 for type 1 diabetes and VGX-3400 for influenza, both licensed from Inovio. The activities related to development of new drugs and CMO businesses were initiated prior to Inovio and VGXP’s involvement with VGX Int’l. Neither Inovio nor VGXP were involved in the design or redesign of these activities subsequent to any business relationship with VGX Int’l. Other than Contract Manufacturing services performed by its wholly owned subsidiary (discussed in more detail below), VGX Int’l does not provide any other contract services to Inovio or VGXP.
      • VGX Int’l was not formed as a wholly or majority owned subsidiary of Inovio or VGXP and its related parties. Also, neither Inovio nor VGXP held a significant variable interest in VGX Int’l at or shortly after VGX Int’l’s formation. VGX Int’l was incorporated on January 27, 1976, under the laws of the Republic of Korea. VGXP’s initial investment was in October 2005, long after the incorporation of VGX Int’l. . VGX Int’l was not formed or restructured by others on behalf of Inovio or VGXP and its related parties and there has been no redesign by Inovio or VGXP with respect to the activities and operations of VGX Int’l.
      • Neither Inovio nor VGXP were involved in the creation of the legal structure of VGX Int’l, including ownership of variable interests in VGX Int’l, the nature of those variable interests and the nature of VGX Int’l’s activities. VGX Intl’s operations were not significantly revised at the time of involvement by Inovio or VGXP and, therefore, their involvement should not be considered a redesign of the entity. Employees of Inovio and VGXP are board members, but not actively involved in managing the day to day operations of VGX Int’l, other than Bryan Kim who was appointed CEO in May 2009 of VGX Int’l, for which he is paid a salary and receives customary director compensation. Bryan Kim did not participate in the design or re-design of VGX Int’l. Bryan Kim’s duties with VGXP include exploring and developing market opportunities for VGXP in Asia, developing and coordinating VGXP’s research and development activities in Asia and general oversight of VGXP’s interests in Asia outside of Korea. Young Park, the corporate secretary of Inovio, is a director of VGX Int’l, for which he receives customary director compensation. J. Joseph Kim, the President and CEO of Inovio and VGXP, is a director of VGX Int’l, for which he receives customary director compensation. None of these individuals participated in the design or redesign of VGX Int’l.
2. 2. The legal entity is designed so that substantially all of its activities either involve or are conducted on behalf of the reporting entity and its related parties.
   1. • Inovio, VGXP and VGX Int’l are independent of one another and operate in different segments and commercial territories in the health care industry. The activities performed by VGX Int’l are not performed substantially on behalf of either Inovio or VGXP, but on behalf of a number of global clients and are not substantial to the activities of VGX Int’l as a whole. As noted above, VGX Int’l currently generates two-thirds of its total revenue from its fabric manufacturing business in which neither Inovio nor VGXP participates or collaborates.
      • VGXP and VGX Int’l do collaborate in research and drug development, as they have entered into certain research and development collaboration and license agreements for purposes of pursuing the development of new drugs related to diabetes, gastric cancer and sharing technology in certain jurisdictions. These arrangements do not represent substantially all of the activities of VGX Int’l.
      • In addition, Inovio and VGXP considered the following with respect to VGX Int’l:
        1. The activities and operations of VGX Int’l are not substantially similar in nature to the activities of either Inovio or VGXP due to the significance of the manufacturing activities related to woven and knitted interlinings, which are provided under the brand name of INTERON, and the DNA plasmid contract manufacturing business;
        2. The majority of VGX Int’l’s products and services are not bought from or sold to Inovio or VGXP;
        3. Substantially all of VGX Int’l’s assets were not acquired from either Inovio or VGXP;
        4. Employees of Inovio and VGXP do not receive compensation tied to the stock or operating results of VGX Int’l, except for stock options granted to Bryan Kim (72,500 shares with exercise price of 5,752 Korean won, with expiration date February 21, 2014) and Young Park (70,000 shares with exercise price of 5,752 Korean won, with expiration date February 21, 2014);
        5. Neither Inovio or VGXP are obligated to fund any operating losses of VGX Int’l, if they occur;
        6. VGX Int’l has not outsourced certain of its activities to either Inovio or VGXP other than through research and development and collaboration agreements, which do not represent substantially all of the activities of VGX Int’l;
        7. VGX Int’l conducts research and development activities; however, neither Inovio nor VGXP has the right to purchase any products or intangible assets resulting from VGX Int’l’s activities; and
        8. Neither Inovio nor VGXP have a call option to purchase the interests of the other investors in VGX Int’l and the other investors do not have an option to put their interests to Inovio or VGXP.
3. 3. The reporting entity and its related parties provide more than half of the total of the equity, subordinated debt, and other forms of subordinated financial support to the legal entity based on an analysis of the fair values of the interests in the legal entity.
   1. • Inovio and VGXP together do not provide more than half of the total equity, subordinated debt or other forms of subordinated financial support to VGX Int’l. Neither Inovio nor VGXP are required to absorb some or all of VGX Int’l’s losses, except through VGXP’s 19.65% equity interest at December 31, 2009.
      • During 2009, VGX Int’l recorded sales of $2,138,773 related to DNA plasmid manufacturing from VGXP. These sales represented approximately 18.2% of total sales, 12.2% of total expenses and 6.9% of total equity of VGX Int’l as of December 31, 2009, less than half of the total equity of VGX Int’l. No other subordinated financial support was paid, or is payable, by either Inovio or VGXP to VGX Int’l.
4. 4. The activities of the legal entity are primarily related to securitizations or other forms of asset-backed financings or single-lessee leasing arrangements
   1. • This section of the guidance is not applicable. The activities of VGX Int’l are not primarily related to securitizations or other forms of asset-backed financings or single-lessee leasing arrangements.

Analysis of VGXI, Inc.

• VGXI is a wholly owned subsidiary of VGX Int’l based in Houston, Texas with employees, and is the production facility for VGX Int’l’s contract manufacturing operations. VGXI meets the definition of a business with inputs and processes capable of producing outputs.
• In 2007, VGXP purchased the DNA plasmid contract manufacturing operations, which serviced customers, from Advisys. In June 2008, VGXI purchased the DNA plasmid contract manufacturing line of business from VGXP. No design or redesign of the DNA plasmid contract manufacturing operations was conducted by VGXP subsequent to the acquisition or after the sale of the operations to VGXI. Neither VGXP nor Inovio management had expertise in the area of plasmid manufacturing. All expertise in this area was acquired from the existing Advisys employees, which was transferred to VGXI under the terms of the Asset Purchase Agreement of June 2008. The sale of the DNA plasmid manufacturing assets to VGXI was driven by VGX Int’l’s interest in the assets and VGXP’s interest in rationalizing its focus into a product driven pipeline.
• VGXI, as a separate legal entity, has a provider-client relationship with the VGXP, albeit a most-favored client. As such, VGXI is not obligated to prioritize the VGXP’s orders over any of its other clients. Furthermore, VGXI has from its formation undergone significant redesign as a subsidiary of VGX Int’l. This redesign included turnover in management to provide more global experience, particularly in Asia, and expansion in capacity, including strategies for expanding manufacturing capabilities to Asia.
• Inovio initially assessed whether VGXI qualified as a business that need not be evaluated, to determine if they are a VIE under the requirements of the Variable Interest Entities subsections. However, on the basis that VGX Int’l was involved in the design of the VGXI legal entity and structure as a US wholly-owned subsidiary and VGX Int’l is considered a related party, Inovio determined that it could not take advantage of the business scope exception given its involvement in the design of the entity. Therefore, Inovio considered whether it was required to consolidate VGXI if any of the following in ASC 810-15-14 existed:
  • •  a. The total equity investment at risk is not sufficient to permit the entity to finance its activities without additional subordinated financial support provided by any parties, including equity holders.
      • • VGX Int’l’s investment in VGXI is not sufficient to enable VGXI to finance its operations without additional subordinated financial support. VGXI is dependent upon VGX Int’l for ongoing financial support. All of VGXI’s revenue is derived from DNA plasmid contract manufacturing agreements with several global healthcare companies such as Senesco Technologies, GeoVax, Inc., Bayhill Therapeutics, and Oxford University, not related to Inovio or VGXP. However, VGXI currently operates at a loss and has since inception. The equity held by VGX Int’l does not exceed the estimate of VGXI’s losses, based on previous financial results. In addition, Inovio and VGXP do not have any contractual obligation or financial commitment to fund the operations of VGXI.
    •  b. As a group the holders of the equity investment at risk lack all of the following three characteristics of a controlling financial interest:
      • • • • (1) The direct or indirect ability through voting rights or similar rights to make decisions about an entity’s activities that have a significant effect on the success of the entity. The investors do not have that ability through voting rights or similar rights if no owners hold voting rights or similar rights (such as those of a common shareholder in a corporation or a general partner in a partnership).
            • (2) The obligation to absorb the expected losses of the entity. The investor or investors do not have that obligation if they are directly or indirectly protected from the expected losses or are guaranteed a return by the entity itself or by other parties involved with the entity.
            • (3) The right to receive the expected residual returns of the entity. The investors do not have that right if their return is capped by the entity’s governing documents or arrangements with other variable interest holders or the entity.
        • VGXI is a wholly-owned subsidiary of VGX Int’l, who controls all voting rights. As an investor or group, VGX Int’l has the ability to make significant decisions about VGXI’s activities through regular voting or similar rights, embodied in the common shares it owns. The decision making rights of VGX Int’l are substantive in nature because they affect the revenues, expenses, gains and losses and financial position of VGXI. As VGXI’s parent company, VGX Int’l has substantive decision making abilities including the ability to purchase or sell significant assets and expand operations into new lines of business. All technical expertise regarding the plasmid manufacturing business resides on the management team of VGXI. VGXP does not have any direct or indirect rights through voting or similar rights to make decisions about VGXI activities because substantive decision rights pertaining to the operations are within the scope of the management group and not the board of directors.
        • Additionally, VGX Int’l is expected to absorb expected losses and receive expected residual returns of VGXI, if profitable. VGXI is a wholly owned subsidiary consolidated by VGX Int’l, and therefore VGX Int’l is not shielded from the risk of loss on any portion of their investment in VGXI, or by others that are involved with VGXI. There are no arrangements such as insurance that may protect holders of VGX Int’l from the risk of absorbing losses from VGXI. VGX Int’l has the right to receive residual returns from VGXI as the case may be, through intercompany loans or reimbursement of services performed. Although VGXP and Inovio may have rights, interests or obligations in their transactions with VGXI that may be considered a variable interest, they are not deemed to be the primary beneficiary required to absorb the expected losses or receive expected residual returns from VGX Int’l or VGXI. All of these rights belong to VGX Int’l.
    •  c. The equity investors as a group also are considered to lack characteristic (b)(1) if (i) the voting rights of some investors are not proportional to their obligations to absorb the expected losses of the entity, their rights to receive the expected residual returns of the entity, or both and (ii) substantially all of the entity’s activities (for example, providing financing or buying assets) either involve or are conducted on behalf of an investor that has disproportionately few voting rights. For purposes of applying this requirement, enterprises shall consider each party’s obligations to absorb expected losses and rights to receive expected residual returns related to all of that party’s interests in the entity and not only to its equity investment at risk.
      • • All of the voting interests of VGX Int’l are proportional to the obligations to absorb the losses of VGXI or the rights to receive residual returns, because VGX Int’l owns 100% of VGXI’s outstanding shares. From a variable interest perspective, Inovio and VGXP have a variable interest with VGXI by virtue of the involvement in the design of the entity and various contractual relationships. However, the contractual relationship is not significant to the overall operations and activities of VGXI as it is one of several significant CMO contracts. As discussed above, VGXI and VGXP’s only relationship is the Supply Agreement dated as of June 25, 2008, pursuant to which VGXI, Inc./ VGX Int’l manufactures cGMP plasmid. as discussed above, such that neither Inovio nor VGXP were determined to be the primary beneficiary to consolidate VGXI as a variable interest entity.
• Inovio will expand its disclosures in future filings to elaborate on its consolidation policy and clarify that VGXI is a variable interest entity of which VGX Int’l is deemed the primary beneficiary to consolidate the entity.
• Inovio and VGXP were not determined to be the primary beneficiaries, based on the analysis above, and therefore do not consolidate the operations of VGXI. Inovio will update its disclosures in future filings to clarify the relationship between Inovio, VGXP and VGXI and the determination that they are not primary beneficiaries.

Results of Operations, page 52

• the Company is responsible for the adequacy and accuracy of the disclosure in the filing;
• staff comments or changes to disclosure in response to staff comments do not foreclose the Commission from taking any action with respect to the filing; and
• the Company may not assert staff comments as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

[Inovio Pharmaceuticals, Incorporated]. 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 Corporation] and [VGX Pharmaceuticals Inc.], 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, Incorporated] (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.  [...]

The flu season has gotten off to a late start, allowing people more time to get the annual vaccine before the season's inevitable peak.

But the nation's health authorities and a few scientists in the forefront of vaccine technology say we could be just a year from human trials of a "universal flu shot" that would make the annually reformulated ones obsolete.

Ideally, this universal shot would catch all previous versions of the ever-morphing flu virus, as well as future mutations.

It would take the guesswork out of calculating the shot Americans are urged to get every winter - averting missteps like the one that left the public vulnerable to the swine flu pandemic of 2009- 10 that affected as many as 89 million people.

If trials continue to go as they have at Philadelphia-based [Inovio Pharmaceuticals, Incorporated], officials there say a shot could be available to the public in five years.

Even if those trials fail, national vaccine experts such as [Dr. Gary Jan Nabel (born 1953)] at the National Institutes of Health are hopeful that scientists will succeed in making a shot that works before the decade is out.

"If you went back five years, you would've said then, 'How would we ever get there from where we are?' Now we're all more optimistic, whether it be Inovio or someone else that succeeds," said Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.

Inovio's $3.1 million grant from the NIH is just one of several helping researchers pursue this previously unthinkable possibility. Another grant has gone to The Scripps Research Institute, which has labs in Jupiter and in La Jolla, Calif.

What changed? Technology, and our understanding of how we can neutralize viruses, scientists say.

Nabel cited research, including that at Scripps, that dates back three or four years and pointed the way to how building this one-shot-kills-all vaccine might work.

Shots involve guess work

Until now, doctors have tackled the flu with methods that date back at least 50 years.

Vaccines deliver a decoy, in this case a dead or weakened version of the influenza virus, to stimulate a person's immune system. In other words: Attack what looks like this.

But the flu virus is a master at defense, dressing itself with an outer envelope that can mutate in months. And there are thousands of varieties of influenza, so health authorities each year pick a few they think are most likely to cause the most problems.

"They get together in January or February and look at what's going on in the Southern Hemisphere," said [Dr. Jong Joseph Kim (born 1969)], Inovio's CEO. "They're looking a season ahead and trying to find three strains from thousands of varieties out there.

"They do their best, and they actually have a pretty good success rate."

But when they don't, the consequences are dire.

"We all saw what happened in 2009 with the H1N1 (swine flu) outbreak," the NIH's [Dr. Gary Jan Nabel (born 1953)] said. "There's a great example of where we were all preparing for one type of seasonal flu, and something came in and it was a complete wild card."

"We were caught flat-footed," he added. "There were deaths that could've been prevented if we had a universal vaccine."

The U.S. Centers for Disease Control and Prevention estimates between 8,870 and 18,300 Americans died of swine flu-related causes from April 2009 to April 2010.

[...]

Finding common aspects

It has been known for years that flu viruses could mutate in thousands of ways, but only recently were researchers - including those at Scripps and [Inovio Pharmaceuticals, Incorporated] - able to begin identifying what made them the same, finding antibodies that targeted those parts and understanding how they work.

"We looked at flu viruses for the last 100 years," Inovio's [Dr. Jong Joseph Kim (born 1969)] said. "Because of DNA sequencing, we have a very good database of what strains have been affecting humans."

While there were thousands of viruses, they fell into a few families. Those include the H1N1 swine flu family; some of the more familiar H2N2 and H3N2; and the H5N1, or bird flu - which researchers including Kim describe as a "very scary virus."

Then computers crunched each family's DNA to find what they had in common. Inovio used that data to create what Kim calls its "secret sauce" - a formula that replicates the common elements and gives people vaccinated a broader target for their immune system.

Inovio reports it has successfully tested vaccines for each family of viruses on both animals and humans. The next phase would be to combine them for a universal version.

"That's really the holy grail for vaccine discovery," Kim said.

NIH's [Dr. Gary Jan Nabel (born 1953)] is cautiously optimistic.

"You learn over time that clinical trials are the big hurdle and because you start a trial doesn't mean it will work," he said. "But I think it's not unreasonable to hope."

And he expects someone will cross the finish line in five to 10 years.

Inovio (NASDAQ:INO) just closed a $422 million deal with Roche Pharmaceuticals (OTCQX:RHHBF) changing the whole perception of the company and its technology. The deal covers only two of Inovio's current pipeline of nine drugs. The drugs included in the partnership agreement are INO-5150 for prostate cancer, and INO-1800 for Hepatitis B.

This deal fundamentally revalues Inovio. One of the largest pharmaceutical companies in the world feels that Inovio's DNA vaccine technology, and electroporation technology is worth investing over 400 million dollars in.

Roche feels that INO-5150 and INO-1800 are worth 422 million, leaving us with the question of what is the rest of the pipeline worth? There are 10 other products in Inovio's pipeline. Certainly any honest person would have to say the value of Inovio is much higher than 422 million now, and with today's closing market cap of $458.85 million the company is very undervalued. I believe that the universal Flu vaccine is worth much more then $422 million by itself. I will give a case study later in this article to support this.

Inovio has tuned in to a controversial stock in recent months. Many do not believe its technology will be successfully developed, others speak about its long history and some bad management decisions and plenty of dilution. I would say that all of these are valid concerns.

The deal with Roche announced today gives us the most qualified answer to these questions. One of the largest pharmaceutical companies on the world is saying that it believes Inovio's DNA vaccines will be successful and make it to market, and indeed after careful study, DNA vaccines are worthy of investment and ready to make it to market. Roche is also saying it believes in Inovio's electroporation technology since it is necessary to deliver the two vaccines it partnered on. Further more, this deal gives an already well financed Inovio another $10 million dollars up front and the milestone payments should be enough to keep Inovio financed into the foreseeable future greatly reducing the chances of any more substantial dilution.

Let me give a very quick and accurate history of VGX/Inovio. I mention VGX because that is the root of the current company. Many have mistakenly thought that Inovio is the root of the current company. I have seen many postings about Inovio's 30 year history here and on many message boards as well. It is true that you can trace the history of Inovio back 30 years, butt that is quite misleading.

The current company, which is the VGX/Inovio combination, starts off in 2001 with Joseph Kim and his former teacher/advisor from the University of Pennsylvania Dr. David Weiner. Dr. Weiner is widely credited as the Father of DNA Vaccines. He is the inventor of naked DNA technology. Dr. Joseph Kim did his doctoral dissertation on DNA Vaccines as well and has written many papers in the field.

Back in 2002 VGX's lead drug candidate was VGX 410 for treating HIV which did fail. Few biotech companies do trials while being private. Most that have a failed product weather public or private go out of business. VGX had a total of 3 trials it did in about 3 years and they all failed. The ability of J. Kim to manage these failures and still keep in business and raising private money is a testament to his excellent management and his ability to do much with very little money. He was constantly in touch with his major investors. Good or bad he told it all.

In 2005 VGX decided to take over a publicly listed company in Korea called Dong Il Fabric, and turn it in to VGXI and make it an international division of the company. So VGXI was founded in 2005. Dong Il still operates as a profitable division of VGXI today. Their lead drug for swine flu was licensed from Inovio back in 2009-2010. It is the same flu vaccine that Inovio is having such great results with in the US.

Advisys take over that VGX did in 2006, which brought the company the manufacturing plant in The Woodlands, Texas, and GHRH technology and an animal health division. All of this for less than 6 million dollars, that was purchased mostly with VGX stock. The reason Inovio is still the name of the company is it was the public entity during the takeover. Given it was a known public entity and VGX was not the name was kept. This may have been a mistake. You can view much of this story in my interview with [Dr. Jong Joseph Kim (born 1969)  back in February.  [...]

Now why you should view Inovio as a different entity than the old entities you are taking about is as follows:

1. VGX management took over all but one of the top postings.

1. Most of the current technology that is used by Inovio is VGX technology. Syncon was developed by VGX (David Weiner) as well as the current pipe line which came from VGX. Indeed the Hep C Cervical cancer vaccine carries the test name of VGX 3100. If you go to the Inovio web site you will see many VGX designations on the pipe line.

2. The Inovio drugs have been developed since the takeover have been developed using the Syncon system.

3. The core of the Cellectra Electroporation system came from the VGX electroporation system. The current model is a fusion of the best of Inovio's and VGX"s systems.

4. The majority of the board of directors was replaced by VGX directors. Finally, the head of the Scientific Advisory Board for VGX, Dr. David Weiner is now head of the Inovio Scientific Advisory Board. Dr. Weiner is the inventor of much of the technology Inovio is developing today. Just as important is Dr. Joseph Kim who has worked on much of this technology as well and is the current CEO of Inovio.

All the VGX trials and takeovers, not to mention research and development was accomplished with 40 million in private funding raised by Joseph Kim. This is a testament to Joseph Kim's amazing management and his ability to reinvent the company and turn in different directions as needed.

When you buy Inovio today, much of what you are buying is Dr. Joseph Kim and Dr. David Weiner. These two men head up the technology that Inovio is developing. All investors interested in Inovio should do a good bit of research of both men. Both have long histories and are at the top of their fields.

Next you are looking at their drug pipeline which is extensive. I do not want to cut and paste data from the Inovio web site, so you can find the Investor summary, and pipeline data at this link http://ir.inovio.com.

Let me narrow this down to two easy points. When you buy Inovio you are buying the SynCon system and Inovios's electroporation system Cellectra.

The SynCon system is a "plug n play" construct that allows the construction of DNA vaccines rapidly. Inovio scientists simply plug in the synthetic DNA fragment into this construct to develop the vaccine. This technology can also be licensed to other companies or Inovio is capable of working with companies directly to implement their DNA fragment into a new DNA vaccine. This system is what has allowed Inovio to have such a diverse pipeline with such low development costs. This system also allows vaccines to be developed very quickly.

The ability of the SynCon system to be licensed or Inovio being able to work with other companies for vaccine development is not something I have seen mentioned in the press. This represents an area that Inovio can expand in to any time in the future with no RND and little start up costs.

Synthetic DNA vaccines are substantially cheaper to produce then their current counterparts, and are more stable which allows them to be transported and stored in environments that have limited or less refrigeration. This will allow wider deployment of vaccines in the third world.

It is a given that most of the pipeline is in the Preclinical stage of development. Which is the stage of lab and animal testing. There are four products that are in human trials, three in Phase 1 and one in Phase 2. Details can be found here http://www.inovio.com/clinical-trials/.

With good trial data on HIV recently reported and published in a peer reviewed medical journal and excellent preclinical Flu and Ebola/Marburgh the company has captured more attention then ever.

The real question is what is this worth? While any answer is speculation, we can make educated guesses to help show some valuation. Many people have posted opinions that the vaccine business is a very low value, and therefore any product approved. I could not disagree with this more.

First as stated above Synthetic DNA are substantially cheaper to produce. So with all the market forces being the same the Synthetic DNA vaccines will be much more profitable. I have discussed the cost differential with many industry sources, and the consensus I have gotten is the Synthetic DNA vaccines will be 35 to 45 percent cheaper to produce. This would be a very nice margin improvement for any company and would take the low margin vaccine industry to medium margin all by itself. That is not the only driver of value and profit. The fact that these vaccines will be more effective and carry no chance of infection from the disease you are vaccinating against will build substantial value.

I want to use one of the most common vaccinations that Americans face and talk about the profit potential. My choice is Flu and the vaccine is the Inovio's universal influenza vaccine for seasonal flu INO-3510.

According to ABC News 128 million people in the US received Flu vaccinations in 2011. I think we can see this is huge profit potential. According to the CDC Vaccine Price List retail cost for adult flu vaccine runs between $9.50 and $8.15. Add a fee of about $10 to $15 for getting the shot and that is how much your vaccination costs.

Given that Inovio's vaccine cannot cause you to get the flu, and that the vaccine is a universal flu vaccine, a vaccination will not be needed yearly. A reasonable time frame for vaccination will be about once every 3 years to start. Inovio will be able to charge a substantial premium for their vaccination. The cost for an Inovio vaccine could be as high as $80 per dose. For our purpose here, let us assume that Inovio decides to charge $50 per dose. With $15 added on for getting the shot itself this drives the cost to $65 for an Inovio vaccine every 3 years. This compares very favorably with the same cost of the current vaccine of about $22 per year.

Given these numbers and the additional benefits of the Inovio vaccine, we can easily see Inovio charging as much as $100 for its vaccine alone. The simple reason the vaccine is a universal vaccine and therefore will not be subject to failure by the CDC picking the wrong strains of flu to vaccinate against would make it a fairly easy sale to both insurance companies, businesses and patients. Also consider that fact that the vaccine will be only needed every 3 years (possibly longer), and we can reasonably say that the Inovio vaccine will dominate the market if or when it is released.

Some simple math will help us make a reasonable value for one year. In the first year we will assume that 70% choose the Inovio vaccine over the older vaccines. Also given the lower costs of production and the ability of Inovio to charge a premium price we will say the profit margin to be a reasonable 50%. So we have a cost per dose of $50 at a 50% margin which leaves us with a margin of $25 per shot. 70% of 128 million is 89,600,000 shots leaves Inovio with a hefty two billion two hundred and forty-million (2,240,000,000) profit. That is big money even for Merck and Pfizer.

These numbers are based on Inovio being first to market with a DNA based universal Flu vaccine. It is possible that others could make it to market first, or during the first year and take part of the market.

The disadvantage is with the 3 year vaccination window, you vaccinate the entire US population in 3 years. It is also possible the vaccination window will be pushed to 5 years or more. Of course in this period Inovio is also getting approval in many other countries.

It is also true that other companies are working on Synthetic DNA vaccines for flu as well. Most are not universal vaccines, but a few are. None have demonstrated as good clinical data as the Inovio vaccine yet. Even if another company has just as good a vaccine as Inovio, both will most likely command a substantial premium.

Yes, few vaccines will be given yearly like the Flu vaccine. With Inovio's efficiency in production of its SynCon vaccines which brings costs down substantially over the current vaccines, even once a lifetime vaccines become much more profitable. Finally I would have to ask how much would the homosexual community pay per dose for a successful HIV vaccine. Followed by the heterosexual population. Gardisil costs about $360 for the total of 3 shots needed. I believe an HIV vaccine could command as much.

We have not even covered Inovio's vaccines that treat the disease, and some even prevent and treat. I believe that this portfolio of vaccines will all command substantial price premiums and their low cost of manufacture will also boost profits.

Now on to electroporation. Inovio has a vast patent estate related to this area. They also have the most clinical experience in this area, and they have the best clinical and human results in electroporation so far. Even if all of Inovio's drug pipeline fails, electroporation could easily make the company profitable.

Electroporation is the delivery system Inovio and other companies use for the delivery of DNA based products. So far it has proven superior to other delivery methods for DNA product delivery systems, which include virus delivery methods (often called Vector based) or chemical (often called adjunct) based systems. Given the growth of DNA vaccines as an industry, and other DNA based treatments, few people doubt that DNA vaccines or DNA treatments will make it through FDA approval eventually.

When this happens, a delivery system will be needed. The best delivery system is Inovio's Cellectra and Inovio is working on many more revolutionary methods to make electroporation more effective, easier on the patients and easier and faster to deliver.

The best comparison I can make for this delivery technology would be like owning the patent on the hypodermic needle and syringe today. What would that be worth?

Much has been made about Inovio needing further dilution to execute its business plan. I will point to the last Inovio quarterly report "Based on management's projections and analysis, the Company believes that cash and cash equivalents are sufficient to meet its planned working capital requirements through the first quarter of 2015." The company can also exercise a few million more shares in its current ATM agreement and raise more capital as the stock price increases.

I will also point out that Inovio is only funding 2 out of 12 products on its current pipeline, demonstrating that Inovio has the ability and desire to use outside funding and partnerships.

With all things the Devil is in the details. It is possible that none of Inovio's drug candidates make it to market It is also possible that another company comes up with a better delivery system for DNA base products.

[ TABLE ] 

As you can see from the table above, Inovio burned through almost 11 million dollars last year. The Roche deal takes two drugs that the company was developing on its own and moves the cost of development off Inovio's balance sheet. However, both these drugs were preclinical, which means the development costs were low. Inovio needs to keep an eye on the cash burn or they could run into problems.

Roche give Inovio 10 million dollars up front, which could cover Inovio for another year at the current cash burn. The rest of the deal is in milestone payments. The risk here is that one or both of the vaccines fails to meet a major milestone. This could cause the company to not receive any milestone payments. However, given the nature of DNA vaccines, they will most likely pass the Phase 1 human trials. Specific milestone details are not known yet, and even if they pass Phase 1, they could still miss the milestones set by Roche. I see the most danger past Phase 1. Inovio was financed until the end of 2015 before this deal, the 10 million dollar up front payment should keep them financed for another year on its own, plus any milestone payments. It appears that Inovio's risk is now more drug performance related then financial.

So how much is all of this potential worth? I know it is impossible to accurately rate potential. I do not want to state my personal belief in this area. I will only say that I believe that Inovio is worth much more then $4 and invite you to make your own decision.

• Disclosure: I am long INO.
• Business relationship disclosure: I have had past business relationships with VGX (when it was private). I was an early investor in VGX back in 2002. I was involved in the takeover of Dong Il Fabric, which led to the formation of VGXI. My partner and I did 10% of the bridge financing. I was also involved by investing additional money in the Advisys takeover and the formation of VGX Animal Health. I own 10% of VGX Animal Health, which is a private company (Inovio owns the other 90%). I own a substantial long position in Inovio, as do some of my family. I am not receiving any compensation for writing this article (except from Seeking Alpha).

Health authorities and pharmaceutical companies are planning to test several new vaccines to prevent Ebola infection over the next few months, including one that is taken as a tablet, making it easier to deploy in West Africa. 

The plans signify that a response to the Ebola outbreak is finally gathering steam. It is still unclear if any of these vaccines will work, however, and even if they do, they may not be ready in time to help stem the current epidemic. 

Starting in January, two vaccines will be tested in large studies in the West African countries most affected by the outbreak, the World Health Organization said on Tuesday. At least three other vaccines will begin safety testing in healthy volunteers outside the outbreak zone in the first quarter of 2015. 

One of those three is actually a combination of two inoculations being developed by Johnson & Johnson and Bavarian Nordic, a Danish company. 

Johnson & Johnson announced early Wednesday that it was committing $200 million to the program, including making an equity investment of about $43 million in Bavarian Nordic to help pay for that company’s part in the project. It says it plans to begin safety trials in January and hopes to produce one million doses in 2015, with 250,000 available for broad application in clinical trials by May.

“Typically, you don’t make hundreds of thousands of vaccines before you know what the safety and immunogenicity is,” said Dr. Paul Stoffels, chief scientific officer of Johnson & Johnson. “This time, we will do that.” 

The two most advanced vaccines in terms of development is each undergoing testing in about 250 healthy adult volunteers in the United States and other countries outside the outbreak region. 

One of the vaccines was developed by the National Institutes of Health and GlaxoSmithKline. The other was initially developed by the Public Health Agency of Canada and licensed to [NewLink Genetics Corporation], a company in Iowa. 

The studies, known as Phase 1 clinical trials, are determining if the vaccines are safe and generate an immune response. Preliminary results are expected by the end of the year, Marie-Paule Kieny, the World Health Organization’s assistant director general for health systems and innovation, said in a news conference in Geneva on Tuesday. 

But she said her organization was not waiting for those results. It is already planning the next stage of testing, to be ready to start in January if the vaccines pass the initial tests. Those new trials will take place in the affected countries in West Africa and would involve tens of thousands of doses, she said. 

There are various scientific and ethical issues to be worked out, including who should receive the vaccine and whether it would be ethical to give some participants a placebo instead. Initial studies are likely to involve health care workers but might also involve others at high risk of infection. 

“We are doing everything we can to produce as many doses as we can as quickly as we can,” said Dr. Ripley Ballou, who leads the vaccine effort for GlaxoSmithKline. 

Dr. Ballou said that while Glaxo would not have enough doses to vaccinate millions of Africans against Ebola, there should be enough by sometime next year to help slow the outbreak by protecting health care workers or those close to infected people. 

Dr. Kieny said that three other vaccines would be ready early next year to enter Phase 1 testing, starting with the combination from Johnson & Johnson and Bavarian Nordic. 

A second is being developed by [Inovio Pharmaceuticals, Incorporated], a small company in Plymouth Meeting, Pa. The third is from [Protein Sciences Corporation] of Meriden, Conn., which already sells a flu vaccine. 

Dr. Kieny also said her organization was trying to find out more about vaccines being developed in Russia. 

She did not mention the tablet vaccine, which Vaxart, a privately held company in South San Francisco, Calif., is developing.

Wouter Latour, the chief executive, said in an interview that, after recent discussions with the Food and Drug Administration, the company hoped to start a Phase 1 safety trial toward the end of the first quarter of 2015. 

“This is ideal to bring to bear on the Ebola crisis,” Dr. Latour said. Not only is it not injected but it is stable at room temperature. Some of the other vaccines must be stored at minus 80 degrees Celsius, which might be difficult in parts of West Africa. 

Dr. Latour said Vaxart’s vaccine protected mice against Ebola but is only now being tested in monkeys. But an experimental flu vaccine developed using the same approach has already been tested in a small number of people. It generated immune responses comparable to or even better than approved flu vaccines, the company’s chief scientist said in a presentation last week at the World Vaccine Congress in Brussels. 

Another company, Profectus BioSciences of Baltimore, received federal funding last week to move its Ebola vaccine toward clinical trials.

I'm a bit of an investment geek and a bibliophile, so reading old SEC filings is one of my favorite pastimes, particularly with stocks I take an interest in. The goal being ultimately to make an informed investment decision. Some read like a real-time autobiography of a company as events unfold while others are more akin to a mystery novel. The book of Inovio Pharmaceuticals (NASDAQ:NASDAQ:INO) and OncoSec Medical (NASDAQ:NASDAQ:ONCS) as written in their myriad of filings resembles the latter. Incestuous relationships are not uncommon in the backwoods of developmental biotech, but Inovio's and OncoSec's relationships appear overly promiscuous even by biotech standards.

The Main Characters

• [Dr. Avtar Singh Dhillon (born 1961)] - Dr. Dhillon was previously CEO and president of Inovio. At the time of OncoSec's acquisition of Inovio's non-DNA technology, he was chairman of both companies.

• Punit Dhillon - Avtar's nephew, at the age of 27, was promoted to vice president, finance and operations at Inovio after spending three years with the company. After OncoSec acquired Inovio's non-DNA technology, Punit became OncoSec's president and CEO.

• [Dr. Jong Joseph Kim (born 1969)] - Prior co-founder, president, and chief executive officer of VGX Pharmaceuticals. Mr. Kim became president and CEO of Inovio after Inovio merged with VGX Pharmaceuticals.

• Young Park - CEO, president, and chairman of the board of VGXI. He joined VGX Pharmaceuticals, Inc. as one of the founding members and established VGX International, Inc. in Korea. Mr. Park also served as general counsel and vice president at Inovio Pharmaceuticals and was instrumental in the merger between VGX Pharmaceuticals and Inovio. He was also a board member of VGX International.

Inovio's Lineage

The story starts in the 1990s, before the incestuous corporate hook-ups. Genetronics Biomedical Corporation, the predecessor to Inovio, was working on a new generation of vaccines, called DNA vaccines, that were focused on cancers. Its therapeutic approach included an electroporation-based delivery technology that facilitated delivery and enhanced the potency of preventive and therapeutic vaccines. Electroporation is the application of brief, pulsed electric fields to cells, which causes tiny pores to temporarily open in the cell membrane, which allows the cell membrane to become more permeable to drugs and genes.

Genetronics began 2002 with plans to initiate a Phase III clinical trial using its therapeutic approach to deliver bleomycin, a chemotherapeutic agent, for the treatment of late-stage head and neck cancer after successful earlier studies. In those studies, of the 37 tumors on 25 patients treated only with bleomycin, only one demonstrated a partial clinical response, whereas 17 of the patients having 20 lesions were subsequently treated with bleomycin using electroporation and 55% achieved an overall (complete + partial) clinical response. By all accounts, the therapy looked like a home run.

In December 2004, the company initiated a clinical study to treat melanomas injected with a cytokine gene followed by electroporation. The study was a first for the combined use of DNA with electroporation in humans. And, in January 2005, Genetronics acquired Inovio AS, a Norwegian company with an intramuscular electroporation platform and subsequently changed its name to Inovio Biomedical (presently Inovio Pharmaceutical). During this time, the company had continued developing its DNA vaccines with various partners including Merck (MRK).

Fast forward to 2007, Inovio's Phase III trial had failed due to a lack of efficacy and risks associated with the therapy. Inovio began redirecting its focus exclusively on its gene vaccine platform and began Phase I studies designed to deliver either gene enhanced IL-2 or IL-12 directly to accessible melanoma lesions. By 2008, Inovio was also focusing on DNA vaccines for infectious diseases in addition to cancer and had begun a Phase I trial for the hepatitis C virus.

Enter VGX

VGX Pharmaceutical, a privately-owned pharmaceutical company, and Inovio Biomedical enter a merger agreement in July 2008. It was a merger of equals with similar therapeutic platforms. Two years prior, VGX had entered into a licensing agreement with Inovio to acquire its DNA delivery technology. Importantly, at the time of the merger, VGX Pharmaceutical had a controlling interest in VGX International, a public company listed on the Korean Stock Exchange (VGX International was renamed GeneOne Life Science in 2013). After the merger, the combined company owned 30% of VGX International. VGX Pharmaceutical had also merged with a private, Texas-based company called ADViSYS the year before. ADViSYS had a significant pipeline for DNA delivered therapeutics as well as DNA delivery and cGMP manufacturing capabilities. After that merger, all plasmid manufacturing activities were aligned into VGXI, a wholly-owned subsidiary of VGX International. VGXI was previously bought by VGX International from VGX Pharmaceutical. VGXI's manufacturing facilities located in Texas were the same facilities previously owned by ADViSYS. It's a little convoluted, but the key point is that it appears VGXI ultimately provides all of the DNA molecules for Inovio's DNA vaccines. This point will become important later.

Enter OncoSec

In a prior life, OncoSec was an online inventory management company called NetVentory Solutions (catchy name). On March 1, 2011, NetVentory Solutions changed its name to OncoSec Medical Incorporated. In March 2011, the company completed the acquisition of certain technology and related assets from Inovio Pharmaceuticals. The acquired technology and related assets relate to the use of drug-medical device combination products for the treatment of different cancers. NetVentory Solutions had basically shut down operations in the prior year. And so, OncoSec was born.

The Asset Purchase Agreement with Inovio allowed OncoSec to purchase its non-DNA vaccine and selective electrochemical technology and related assets. OncoSec paid Inovio $3,000,000 over a two-year period and a royalty on commercial product sales related to the technology (The payment schedule was subsequently amended twice, allowing Inovio to acquire warrants to purchase 4 million shares of OncoSec's stock). Under the terms of the agreement, OncoSec granted Inovio an exclusive, worldwide license to certain of the acquired technology patents in the field of use of electroporation. So basically OncoSec obtained the "non-DNA" electroporation technology platform that can also be used to efficiently deliver a chemotherapeutic or cytokine agent for the treatment of cancer while Inovio maintained the DNA vaccines and technology platform for delivery.

Pursuant to a Stock Purchase Agreement dated in February, 2011 (a month before the Inovio deal), Avtar Dhillon acquired 18.8% of the OncoSec from prior directors. Avtar Dhillon's nephew, Punit Dhillon, who was Inovio's VP of finance and operations, was installed as OncoSec's president and CEO. He also purchased 8.3% of OncoSec's stock from the same directors.

Avtar Dhillon's background was as a venture capitalist in the biotech field before joining Inovio. It appears he used those skills to take control of a shell company (NetVentory Solutions), change the name (OncoSec) and then used the new company to purchase non-strategic assets from his other company (Inovio).

Of interest, shortly after Avtar Dhillon closed his deal with OncoSec, an independent board member at Inovio gave his resignation [See https://www.sec.gov/Archives/edgar/data/1055726/000119312511099778/dex171.htm ] citing, "the 'freedom to act' and 'aggressiveness' that management wishes to have, as it relates to the Board, in my opinion is not consistent with good governance, especially for a publicly traded company."

OncoSec's Trials

By OncoSec's fiscal year ending July 31, 2011, after only five months in existence, it was touting clinical trials for both immunotherapy and chemotherapy. The 10-K indicated the company had completed its immunotherapy Phase I trial and expected to begin a Phase II trial by year end. Since there's no way a Phase I trial could be initiated and completed in five months, OncoSec was obviously touting Inovio's 2008 Phase I immunotherapy trial of Interleukin-12 in patients with metastatic melanoma.

The 10-K also stated OncoSec's chemotherapy approach had been developed up to Phase III clinical trials for the treatment of head and neck cancer using bleomycin. Apparently OncoSec was referencing Inovio's failed trial mentioned earlier without indicating that the independent data monitoring committee's recommendation to cancel the trial due to concerns about efficacy and serious adverse events, including higher mortality rates.

OncoSec's Agreement With VGXI

OncoSec had acquired "non-DNA" technology from Inovio, but immediately began focusing on DNA-based immunotherapy and had touted a completed Phase I immunotherapy trial. Something was missing, namely its access to DNA vaccines. That void was corrected when OncoSec inked a deal with VGXI in June 2012. As a reminder, VGXI is a subsidiary of a company controlled by Inovio and is also the supplier of Inovio's plasmid DNA.

Interestingly, VGXI PR'ed OncoSec's results of its melanoma trial in 2011. The same exact trial results that were PR'ed by Inovio in 2008! Apparently, OncoSec's "non-DNA" acquisition included OncoSec's adoption of Inovio's DNA immunotherapy trial. Given the success of the Phase I trial, it begs the question what happened between 2008 and 2011 and why would Inovio relinquish an ongoing, successful study? The answer may lie in the fact that the trial was investigator-sponsored. In other words, a commercial entity wasn't the sponsor. That changed in November 2012 when OncoSec took over the trial from the existing sponsors.

Regardless of how it was pieced together, during 2012 using Inovio's Phase I melanoma trial, OncoSec began three Phase II trials in melanoma, Merkel cell carcinoma and cutaneous T-cell lymphoma.

Interim data from the Phase II melanoma trial was presented in 2014 which reported that of the 27 patients who were evaluable, an objective response rate of 33% was observed, with 11% of patients having a complete response. Regression of non-injected lesions was seen in 62% of 21 patients with evaluable lesions. Since those initial results, OncoSec continues to advance its electroporation IL-12 studies in multiple Phase II trials including trials with combination drugs such as Pembrolizumab (Merck's anti-PD-1 therapy, KEYTRUDA). Overall results to date are summarized below based on OncoSec's last investor presentation:

Initial results look impressive, however, it should be noted the failed electroporation trial using chemotherapy that OncoSec initially cited in one of its first filings had early results that surpassed these results using IL-12. Time will tell if OncoSec's final trial results will have a better outcome.

Inovio Inks Lucrative Deals With Large Pharma

As OncoSec moved forward with its electroporation IL-12 trials, Inovio continued to progress its DNA vaccines for cancers and infectious diseases, including a couple of substantial partnering opportunities.

The first substantial partnership was in September 2013 when Inovio entered into an exclusive worldwide license agreement with Roche (OTCQX:RHHBY) to research, develop and commercialize INO's DNA immunotherapies targeting prostate cancer and hepatitis B. Under the terms of the agreement, Roche made an upfront payment of $10 million. Roche will also provide preclinical R&D support and payments for near-term regulatory milestones as well as payments upon reaching certain development and commercial milestones potentially up to $412.5 million. Additionally, Inovio is entitled to receive up to double-digit tiered royalties on product sales.

The most recent partnership was announced with MedImmune in August of this year [See https://www.astrazeneca.com/media-centre/press-releases/2015/medimmune-inovio-pharmaceuticals-cancer-vaccine-10082015.html# ] . Under the agreement, MedImmune will acquire exclusive rights to Inovio's INO-3112 immunotherapy, which targets cancers caused by human papillomavirus types 16 and 18. INO-3112 is in phase I/II clinical trials for cervical and head and neck cancers. These papillomavirus types are responsible for more than 70 percent of cervical pre-cancers and cancers. The deal provided Inovio with $27 million upfront and milestone payments up to $700 million over time.

Stock Performance

Even with Inovio's partnering success, neither company has been able to deliver value for shareholders over the past two years as the graph below reflects; however, OncoSec has been particularly punitive with its market cap declining by over two-thirds in the past year from approximately $150 million to $47 million.

Financial Condition

Inovio ended the third quarter with approximately $171 million in cash and short-term investments providing a cash runway well into 2018.

OncoSec, on the other hand, had cash of approximately $27 million. In addition, the company netted $6.9 million from a direct offering in November. ONCS used about $4.5 million in operations over the last quarter so, assuming similar expenses going forward, its cash runway is into 2017. That said, biotechs like to raise cash before they need it so I anticipate additional capital raises in 2016.

Conclusion

When you start analyzing an investment, you never know where the road will lead. The story of Inovio and OncoSec is over two decades in the making and still just in the beginning chapters. After a thorough read, I would not invest in OncoSec due primarily to a lack of credibility. If I had completed my analysis a year earlier, before OncoSec had lost two-thirds of its value, my recommendation would be to short the stock. That thesis may still have merit even at these levels.

Inovio, on the other hand, has a strong balance sheet and financial support from large pharma. After developing the science over a long period of time, either by pure luck or perseverance, it appears its current therapies have considerable potential, which has been somewhat validated by the partnerships with Roche and MedImmune. The declining stock price over the past 18 months could present a nice buying opportunity if that potential eventually comes to fruition.

A vaccine against the Zika virus could be in production later this year, said a Canadian developer who previously led the effort to develop the ZMapp treatment for Ebola virus disease.

Gary Kobinger, head of vector design and immunotherapy in the special pathogens programme at Canada’s National Microbiology Laboratory, told Reuters, “This vaccine is easy to produce. It could be cranked to very high levels in a really short time.”

Kobinger’s laboratory is collaborating with a team at the University of Pennsylvania led by David Weiner and with Inovio Pharmaceuticals and GeneOne Life Science of South Korea.

Inovio’s chief executive, Joseph Kim, called Kobinger’s timeline aggressive but possible. “I believe this will be the first to go into human testing. We believe we’re ahead of the pack in the race for a Zika vaccine,” he told Reuters.

Kobinger later told the Canadian Broadcasting Corporation that his prospective Zika vaccine was already in clinical production. He said, “We hope that all the testing, as in the past, will be acceptable to regulators like Health Canada and the FDA [US Food and Drug Administration], and we’ll be able to start enrolling volunteers, with their approval, and start a stage 1 clinical trial by mid or late summer. That’s a goal of course. We don’t know if we can achieve it, but I think we can.”

Asked when the vaccine might be available for use in humans, Kobinger replied, “Maybe by the fall. At least in 2016. It doesn’t mean the vaccine is all of a sudden available for the entire population. The goal is to do our best but to be ready if there’s an emergency.”

Other groups working on Zika vaccines were less bullish about early prospects for a vaccine, noting the long timeline usually associated with vaccine development. Sanofi-Pasteur and GlaxoSmithKline have both been exploring the possibility of a Zika vaccine but warned that it would take several years to reach production. Sanofi-Pasteur’s new dengue vaccine, approved last month, was 20 years in the making.

Anthony Fauci, head of the US National Institute for Allergy and Infectious Diseases, told NBC News that his agency was working on two vaccines but that it was likely that these would take three to five years to reach full production, though clinical testing might begin later this year. That schedule, unusually fast for a vaccine, was possible because one candidate was based on an existing vaccine against dengue and the other on a vaccine against West Nile virus, he said.

Brazil’s president, Dilma Rousseff, this week rebuked the country’s health minister, Marcelo Castro, for telling journalists that the country was “badly losing” the battle against the Aedes aegypti mosquito, even as 220 000 military personnel led eradication efforts. Rousseff said that Brazil’s Butantan Institute was working to develop a vaccine “in record time,” but its director of clinical trials, Alexander Precioso, warned the BBC that a wait of three to five years was still likely.

For the moment, she said, the battle must focus on the mosquito. Brazil and the United States are examining approaches that involve the release of genetically modified male mosquitoes to interrupt reproduction.

Brazil’s Supreme Court will hear a petition in late March to exempt women found to be carrying fetuses with microcephaly from the country’s strict prohibition on abortion. An exemption already exists in the case of anencephaly.

Public Health England has warned men to wear condoms for a month after returning from any of the countries where the Zika virus is present, now numbering 23 and rising. Sexual transmission of Zika has been documented,1 and the virus has been isolated in sperm,2 though this is not believed to be a major factor in its spread.

"[...]  A handful of smaller companies have also said they are working on Zika vaccines, some on more aggressive timelines. One team, a collaboration between [Inovio Pharmaceuticals, Incorporated], the South Korean company [GeneOne Life Science, Inc.] and academic researchers in Canada and the United States, has said its product could be ready for emergency use by this fall. Two other companies, Hawaii Biotech and the [Protein Sciences Corporation], also announced plans for a Zika vaccine. [...] "

MADISON, Wis. — The Zika virus thrives in tropical climates. But it is also growing in this cold-weather city — up a flight of stairs, past a flier for lunchtime yoga and behind a locked door. That is where scientists working in a lab for Takeda, the Japanese drug company, inspect and test vials of the virus.

They are engaged in an all-out race to halt Zika, a disease that has set off worldwide alarm because of its links to severe birth defects. Day and night, these researchers are trying to crack the code to the virus.

“We’re slaves to the cells,” Jeremy Fuchs, a senior researcher at the lab, said.

And they are far from alone. Perhaps never before have so many companies and government organizations worked so quickly to develop a vaccine from scratch. Vaccines usually take a decade or more to develop. But researchers say a Zika vaccine could be available as early as 2018, in what would be a remarkable two-year turnaround.

More than a dozen companies are on the hunt, in addition to government stalwarts like the National Institutes of Health. To get ahead, some teams are employing innovative technologies that rely on splicing DNA, a method that has the potential to revolutionize the development of vaccines but that has never before been approved for use in humans.

The prestige of solving the puzzle and the chance to save lives are possible rewards. For the companies, another motive is the potential for significant profit. Unlike many recent viral outbreaks, which have been confined to poor areas, Zika has spread to countries like Brazil and the United States, with millions of wealthy people and governments that can afford public vaccination campaigns.

“It’s highly unusual,” said [Dr. Thomas Patrick Monath (born 1940)], the chief scientific officer and chief operating officer of [NewLink Genetics Corporation], one of the companies developing a vaccine. “It reflects the big opportunity and public health need, and also the fact that we have more, different technologies available today.”

But meeting the ambitious timeline is far from guaranteed. To keep the fast pace, some clinical trial organizers are trying to start their tests in South America over the next few months, when Zika infection rates are expected to be at their height there.

The timing is crucial. An outbreak of Zika provides an ideal testing ground for a vaccine, so the preventive medication can be evaluated in a population exposed to the virus. Researchers will know in short order whether the vaccines being tested are effective.

If they miss the window, a vaccine could be delayed for a year or more — a result that could lead to millions more people becoming infected with the virus.

“It’s a race against nature,” said Michel De Wilde, a vaccine research consultant and former executive at Sanofi, a French vaccine manufacturer.

The virus, spread by mosquitoes and sexual intercourse, has now been reported in more than 70 countries. This summer, it landed in the United States, spreading quickly in Puerto Rico and turning up in Miami. Government officials have advised pregnant women to avoid parts of Miami where the virus is active. In a sign that Zika will be a continuing threat, on Friday the World Health Organization lifted its nine-month emergency declaration and said it would shift to a longer-term effort to combat the virus.

By September, after acrimonious debate and a long delay in Congress, President Obama approved a $1.1 billion spending package to fight the virus. About $400 million of the money will go toward developing a vaccine and diagnostic tests.

The escalation of attention has been remarkable. Identified nearly seven decades ago, Zika was once considered mostly harmless, because about 80 percent of people who are infected show no symptoms.

But about 18 months ago, Brazilian officials began to sound alarms that it was to blame for an otherwise mysterious outbreak of babies born with microcephaly, or unusually small heads and malformed brains. Around the same time, heartbreaking photographs of children born with the condition shot around the globe.

Dr. Barney S. Graham, deputy director of the Vaccine Research Center at the N.I.H, was at a meeting in July 2015 when he learned of the threat. A Brazilian doctor pulled him aside at the meeting in Bethesda, Md., which had been called to discuss chikungunya, another tropical disease.

“I know we’re here about chikungunya,” Dr. Graham said the doctor told him. “But I really want to tell you about Zika virus.”

Within months, the link seemed increasingly clear, and public health officials predicted that the virus would probably infect millions of people. In December, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases at the N.I.H., called a meeting with the top members of his vaccine staff.

[]Similar meetings were occurring elsewhere in the vaccine world — at small companies like [Inovio Pharmaceuticals, Incorporated] and [NewLink Genetics Corporation], in the offices of big manufacturers like GlaxoSmithKline and Sanofi, and at the Walter Reed Army Institute of Research, which is a few miles from the N.I.H. campus in Bethesda, where Dr. Fauci’s team works.

“I said, all hands on deck,” Dr. Fauci recalled. “We have a serious problem here. We’ve got to really move.”

High Stakes and Confidence

No single person directs an operation as widespread as the race for the Zika vaccine. But Dr. Fauci certainly sits near the center of it and comes with a singular perspective.

An immunologist, Dr. Fauci, 75, has led the National Institute of Allergy and Infectious Diseases for more than three decades, playing a role in nearly every major disease outbreak since the 1980s.

And to hear him tell it, the Zika virus does not stand much of a chance.

“Without being presumptuous, most of us in the field feel that we will get a vaccine for Zika,” Dr. Fauci said recently, his staccato Brooklyn accent underscoring his confidence. “So it’s really a question of what’s the best one, how quickly can you get it, is it safe, and is it scalable?”

But he also knows the stakes.

“For a pregnant woman,” he said, “it’s absolutely devastating in its potential impact.”

His team, and the others chasing a Zika vaccine, started with a couple of big advantages. For one, the economic incentives are clear. The first company to develop an effective vaccine will win a toehold in a market that could ultimately reap billions in profit. And because governments are paying for some of the early development, the financial risk is limited.

Also, the disease belongs to a family of viruses known as flaviviruses, which scientists have been battling for more than a century. Vaccines already exist for some of these viruses, such as yellow fever, Japanese encephalitis and dengue.

Another good sign: Adults infected with Zika seem to fight off the illness on their own, meaning the human body, if given the right tools, already has the resources to defeat it.

The vaccine hunters had several options. The tried-and-true method is what is known as a killed vaccine, in which a dead virus is injected into the body. The body then builds its defense against the virus in a way that also protects against the live version. This is how many vaccines work, including those for polio and the flu.

Several teams, including those at Takeda and one at Walter Reed, chose that path. Walter Reed’s candidate entered early clinical trials in this month. Sanofi has signed on to bring that product to market.

The advantage of the killed vaccines is that they are reliable. Several vaccine specialists said they were confident a Zika vaccine using this method would succeed. The downside is that developing one takes time, sometimes decades.

Other teams, including Dr. Fauci’s scientists at the N.I.H., decided on a newer approach. It involves manufacturing a harmless piece of the virus’s DNA, the molecule that acts like an instruction manual for the body. Once injected, the DNA tells human cells to make Zika proteins. Those proteins then assemble themselves into harmless viruslike particles that trick the body into developing antibodies that can fight the disease if it arrives.

It is a startlingly simple and fast approach. Dr. Fauci’s team created a prototype that it could begin testing in mice within weeks.

“You can jump in right away,” he said.

However, DNA vaccines are largely unproved in humans. While the technology has been approved for animals, none of the vaccines have been approved for humans. A vaccine developed by the N.I.H. to prevent West Nile, another virus related to Zika, succeeded in early trials but never completed trials and was not brought to market because researchers could not find a drug company that was interested.

Part of the reason DNA vaccines are tricky, researchers say, is because the vaccine’s DNA must reach the nucleus of a person’s cells before it can begin instructing them to make Zika proteins. When the vaccine is injected into the body, not all of it reaches the nucleus, lowering its effectiveness.

To solve this problem, some companies are trying a similar method that uses RNA, a molecule in the body that is more flexible than DNA. Among the things it can do is carry out, on its own, the instructions contained in DNA. The vaccine would not need to reach a cell’s nucleus to trigger the immune response.

GlaxoSmithKline and Moderna Therapeutics, using government grants, are working on RNA vaccines for Zika that are still in their early stages.

Testing in Zika Zones

If one or more Zika vaccines are successful, it is unclear who would ultimately get them. The medication could be used only during outbreaks, or it could become routine in some parts of the world.

Early trials of the DNA-based vaccine developed by the N.I.H. are underway, and studies have begun in Puerto Rico of a similar vaccine being developed by [Inovio Pharmaceuticals, Incorporated].

The next step will be to test the vaccines in a larger pool of people who live where Zika is present. That stage must be intricately set so that the trials occur at just the right moment, at the height of summer in Latin America, which starts in December.

Not a day can be wasted. The N.I.H.’s trial coordinators are setting up trial sites at more than 20 locations in Central and South America. Once the trials begin, the coordinators will monitor local Zika cases, moving resources to sites of outbreaks and away from places where the virus is quiet.

Researchers say they are taking a lesson from the Ebola outbreak of 2014, which also spurred a race for a vaccine. In that case, the outbreak was brought under control before many of the trials could take place.

“All of us felt like we kind of really missed the boat with Ebola,” said Col. Nelson Michael, who is leading the Zika vaccine effort at Walter Reed. “We brought troops too slowly into the fight.”

In a clinic at the University of Maryland School of Medicine in Baltimore in September, several volunteers waited hours in a hallway to be among the first to receive the experimental DNA vaccine being developed by the N.I.H.

Some read college textbooks, others browsed Facebook.

Jen Wenzel, a volunteer and a postdoctoral fellow in neuroscience, said she signed up out of curiosity — and to make extra money. Volunteers are paid as much as $1,600 if they complete the study.

When it was her turn, Ms. Wenzel winced and looked away from the needle about to deliver the vaccine. “Take a deep breath,” said a nurse, who then quickly jabbed the needle into Ms. Wenzel’s arm, making her gasp in surprise.

And with that, Ms. Wenzel became the 29th person at the University of Maryland, and one of only dozens worldwide, to have received a potential Zika vaccine. Over the next two years, she will return to the clinic for follow-up tests to see how well it works.

Of course the researchers chasing a vaccine — and the many millions of people concerned about catching the virus — hope to have an answer long before then.

PLYMOUTH MEETING, Pa., Jan. 23, 2020 /PRNewswire/ -- [Inovio Pharmaceuticals, Incorporated] today announced [The Coalition for Epidemic Preparedness Innovations (CEPI)] has awarded Inovio a grant of up to $9 million to develop a vaccine against the recently emerged strain of coronavirus (2019-nCoV) that has killed numerous people and infected hundreds more in China to date. This initial CEPI funding will support Inovio's preclinical and clinical development through Phase 1 human testing of INO-4800, its new coronavirus vaccine matched to the outbreak strain. CEPI previously awarded Inovio a grant of up to $56 million for the development of vaccines against Lassa fever and Middle East Respiratory Syndrome (MERS), also caused by a coronavirus.

Inovio's participation in this developing effort is based on the ideal suitability of its DNA medicine platform to rapidly develop a vaccine against an emerging virus with pandemic potential, proven vaccine development capabilities and a strong track record of rapidly generating promising countermeasures against previous pandemic threats. Inovio was the first to advance its vaccine (INO-4700) against MERS-CoV, a related coronavirus, into evaluation in humans. Inovio is currently preparing to initiate a Phase 2 vaccine trial for INO-4700 in the Middle East where most MERS viral outbreaks have occurred.

In a recently published paper in Lancet Infectious Diseases, Inovio's Phase 1 study of its MERS-CoV vaccine demonstrated it was well tolerated and furthermore induced high levels of antibody responses in roughly 95% of subjects, while also generating broad-based T cell responses in nearly 90% of study participants. Durable antibody responses to INO-4700 were also maintained through 60 weeks following dosing.

[Dr. Richard Jones Hatchett IV (born 1968)], CEPI's CEO, said, "Given the rapid global spread of the 2019-nCoV virus the world needs to act quickly and in unity to tackle this disease. Our intention with this work is to leverage our work with Inovio on the MERS coronavirus and rapid response platform to speed up vaccine development."

[Dr. Jong Joseph Kim (born 1969)], Inovio's President & CEO said, "We're extremely honored to expand our partnership with CEPI to tackle this new threat to global public health. Our DNA medicine platform represents the best modern day approach to combatting emerging pandemics. We have already demonstrated positive clinical outcomes with our vaccine against MERS-CoV, another coronavirus. Importantly, following the Zika viral infection outbreak, Inovio and our partners developed a vaccine that went from bench to human testing in just seven months – the fastest vaccine development on record in recent decades. We believe we can further improve upon this accelerated timeline to meet the current challenge of the emerging Chinese coronavirus 2019-nCoV."

Inovio's collaborators in this coronavirus vaccine development include the Wistar Institute, [VGX International], a fully owned subsidiary of [GeneOne Life Science, Inc.] (KSE: 011000), and Twist Bioscience (NASDAQ: TWST).

• About CEPI  :   CEPI is an innovative partnership between public, private, philanthropic, and civil organisations launched in Davos in 2017 to develop vaccines to stop future epidemics. CEPI has received multi-year funding from Norway, Germany, Japan, Canada, Australia, and the Bill & Melinda Gates Foundation, and Wellcome. CEPI has also received single-year investments from the government of Belgium and the United Kingdom. The European Commission forsees substantial financial contributions to support relevant projects through EC mechanisms. CEPI has reached over US$ 750 million of its $1 billion funding target. Since its launch in January 2017, CEPI has announced three calls for proposals. The first call was for candidate vaccines against Lassa virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Nipah virus. The second call was for the development of platforms that can be used for rapid vaccine development against unknown pathogens. The third call is for candidate vaccines against Rift Valley fever and Chikungunya viruses. To date, CEPI has committed to investing over $310 million in 12 vaccine candidates (five against Lassa virus, four against MERS-CoV, three against Nipah virus) and two vaccine platforms to develop vaccines against Disease X.
• About Inovio Pharmaceuticals, Inc.  :   Inovio is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat, cure and/or protect people from diseases associated with HPV, cancer, and infectious diseases. Inovio is the first and only company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to safely produce a robust immune response to destroy and clear high-risk HPV 16 and 18, which are responsible for 70% of cervical cancer, 90% of anal cancer and 69% of vulvar cancer. In addition to HPV, Inovio's optimized plasmid design and delivery technology has been demonstrated to consistently activate robust and fully functional T cell and antibody responses against targeted cancers and pathogens. Inovio's most advanced clinical program, VGX-3100, is in Phase 3 development for the treatment of HPV-related cervical pre-cancer. Also in development are Phase 2 immuno-oncology programs targeting HPV-related cancers and GBM, as well as externally funded platform development programs in Zika, MERS, Lassa, and HIV. Partners and collaborators include ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense Advanced Research Projects Agency, GeneOne Life Science, HIV Vaccines Trial Network, Medical CBRN Defense Consortium (MCDC), National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Regeneron, Roche/Genentech, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. For more information, visit www.inovio.com.

In a swift response to the spread of a new coronavirus in China, global outbreak preparedness group Coalition for Epidemic Preparedness Innovations (CEPI) unveiled funding for three early-stage vaccine programs. 

Moderna this week disclosed that it’s working with federal researchers on a candidate, and now it'll have financial backing from CEPI. Pennsylvania-based Inovio Pharmaceuticals scored $9 million in funding for its own program, and CEPI is further expanding a partnership with the University of Queensland.

For Moderna, CEPI’s funding will cover manufacturing for an mRNA vaccine candidate against the new coronavirus strain. The work will be further supported by federal researchers at the National Institute of Allergy and Infectious Diseases (NIAID) who will conduct preclinical tests and a phase 1 study. 

Separately, the CEPI grant will cover Inovio's development costs through phase 1 for the biotech's candidate, dubbed INO-4800. The vaccine is based on Inovio’s DNA medicine platform that the company says enables rapid development of a vaccine against emerging threats. 

Inovio and CEPI already have some history. In 2018, CEPI awarded Inovio up to $56 million over five years for its work on Middle East respiratory syndrome (MERS) and Lassa fever vaccine candidates.  

Inovio was involved in the Zika outbreak response as well and reached human testing with its vaccine candidate in just seven months, CEO Joseph Kim said in a statement. 

“We believe we can further improve upon this accelerated timeline to meet the current challenge of the emerging Chinese coronavirus 2019-nCoV,” he added. 

The company has routinely jumped into emerging disease research, but has yet to take a product through to an approval. Moderna doesn't have any approved drugs or vaccines, either.

The coronavirus has already killed 26 people and infected at least 881 people in Wuhan, China state TV reported this week.

Aside from those vaccine efforts, Baylor College of Medicine has a program to develop new coronavirus vaccines for severe acute respiratory syndrome and MERS, Peter Hotez, dean for the National School of Tropical Medicine, told FiercePharma. In conjunction with NIAID, plus scientists in New York and Shanghai, the team is testing whether the vaccines could protect against the new coronavirus. 

CEPI formed in 2017 as a partnership between governments, philanthropists, pharma companies and others to address a gap in vaccine development funding after Ebola and Zika caught the world off guard. The group set out to raise $1 billion to fund research against numerous threats, and, so far, it has granted $450 million. 

Corporate History and Headquarters

We have been a leader in advancing the capabilities of DNA-based immunotherapies to treat infectious diseases and cancers going back to the original incorporation of Viral Genomix, Inc. under the laws of Delaware on April 17, 2000. We were renamed VGX Pharmaceuticals, Inc. on May 31, 2006. On February 21, 2007, VGX Pharmaceuticals acquired Advisys, Inc., a company possessing DNA and electroporation technology, through an asset purchase agreement. On April 14, 2007, VGX Pharmaceuticals entered into an exclusive license agreement with the Trustees of the University of Pennsylvania related to therapeutic and prophylactic DNA vaccines developed by Professor David B. Weiner at the University of Pennsylvania School of Medicine.

Recognizing the value of electroporation delivery technology, devices, and patents in advancing DNA-based immunotherapy products, on June 1, 2009, VGX Pharmaceuticals completed a merger with Inovio Biomedical Corporation, a publicly listed company focused on electroporation delivery technology.

Inovio Biomedical Corporation started as Biotechnologies & Experimental Research, Inc. and was incorporated on June 29, 1983 in California to create products for the research marketplace. The company changed its corporate name to BTX, Inc. on December 10, 1991, and to Genetronics, Inc. on February 8, 1994. On April 14, 1994, Genetronics, Inc. became a public company through a share exchange agreement with Consolidated United Safety Technologies, Inc., a company listed on the Vancouver Stock Exchange under the laws of British Columbia, Canada. The company changed its name to Genetronics Biomedical Ltd. on September 29, 1994. Genetronics, Inc. remained as a wholly owned operating subsidiary. On September 2, 1997, the company listed on the Toronto Stock Exchange. On December 8, 1998, the company listed on the American Stock Exchange (now NYSE MKT) and voluntarily de-listed from the Toronto Stock Exchange on January 17, 2003. On June 15, 2001, Genetronics Biomedical Ltd. completed a change in jurisdiction of incorporation from British Columbia, Canada, to the state of Delaware and became Genetronics Biomedical Corporation. On January 25, 2005, Genetronics Biomedical Corporation acquired Inovio AS, a gene delivery technology company located in Norway. On March 31, 2005, Genetronics Biomedical Corporation was renamed Inovio Biomedical Corporation.

The merger between VGX Pharmaceuticals and Inovio Biomedical Corporation was effected pursuant to the terms of an Amended and Restated Agreement and Plan of Merger dated December 5, 2008, as further amended on March 31, 2009. On May 14, 2010, the combined entity changed its corporate name to Inovio Pharmaceuticals, Inc. We conduct our business through our United States wholly-owned subsidiaries, VGX Pharmaceuticals, LLC and Genetronics, Inc.

Our corporate headquarters are located at 660 W. Germantown Pike, Suite 110, Plymouth Meeting, Pennsylvania 19462, and our telephone number is (267) 440-4200.

[...]

Not long after researchers completed their work with mice, guinea pigs, ferrets and monkeys, Human Subject 8, an art director for a software company in Missouri, received an injection. Four days later, her sister, a schoolteacher, became Subject 14.

Together, the sisters make up about 5 percent of the first ever clinical trial of a DNA vaccine for the novel coronavirus. How they respond to it will help determine the future of the vaccine. If it proves safe in this trial and effective in future trials, it could become not only one of the first coronavirus vaccines, but also the first DNA vaccine ever approved for commercial use against a human disease.

Hundreds of experimental vaccines for the new coronavirus are currently being developed across the world. These vaccines’ ability to advance will depend not only on science and funding, but also on the willingness of tens of thousands of healthy people to have an unproven solution injected into their bodies.

In many of these studies, the vaccine recipe isn’t the only thing on trial. Gene-based vaccines — and at least 20 coronavirus vaccines in development fall into this category — have yet to make it to market. Should one end up in doctors’ offices amid the rush to shield billions from Covid-19, it would represent a new chapter for vaccine development.

And though vaccine research has never moved this quickly — potentially meaning enhanced risks for volunteers — it has never been easier to recruit subjects, according to Dr. John E. Ervin, who is overseeing the DNA vaccine trial at the Center for Pharmaceutical Research in Kansas City, Mo., in which the sisters are involved. For the Phase 1 trial of the vaccine, which was developed by Inovio Pharmaceuticals, 90 people applied for the 20 slots in Kansas City.

“We probably could charge people to let them in and still fill it up,” he said. (In fact, the participants were paid per visit.)

The art director, Heather Wiley of Independence, Mo., said that realizing she would make around $1,000 for her participation was a bonus, not her primary motivation.

“I’m in the middle of the country trying to process 100,000 dead and how all those people died alone,” she said. Her fears for her family left her so anxious she couldn’t sleep.

While looking up vaccines, she stumbled on Dr. Ervin’s trial, which was recruiting volunteers just 20 miles from her. Two months shy of 50 and healthy, she qualified.

Step 1: A shot with computer-engineered DNA

Two weeks later, Dr. Ervin was injecting Ms. Wiley just beneath the skin of her upper arm with a transparent liquid containing the experimental vaccine.

The solution contains a computer-engineered DNA sequence, which includes genetic instructions for building the spike that makes the coronavirus so superb at entering its host’s cells. Cells are equipped to read genetic instructions; that’s just part of what they do. When these instructions arrive, the cells follow them and make the very same spike protein present on the surface of the coronavirus now wreaking havoc on the world.

The immune system responds to these spike proteins, now being manufactured by the body, and mounts a defense. These spike proteins are harmless; they are not attached to a virus. But the hope is that in the future, should a virus wearing spikes with that same genetic code attempt to invade, the immune system’s arsenal would be prepared.

[Inovio Pharmaceuticals, Incorporated] researchers engineered the vaccine in just three hours, according to Kate Broderick, the company’s senior vice president for research and development. Or, rather, their computer algorithm did: On Jan. 10, when Chinese researchers released the genetic code of the novel coronavirus, the team ran the sequence through its software, which popped out a formula.

This timeline struck some in the financial sector as too good to be true. Citron Research, which advises investors on companies to bet on, called Inovio “the Covid-19 version of Theranos,” referring to the blood-testing device company that imploded as its supposedly revolutionary product was revealed to be a hoax.

“Much like Theranos, Inovio claims to have a ‘secret sauce’ that, miraculously, no pharma giant has been able to figure out,” Citron Research wrote. “This is the same ‘secret sauce’ that supposedly developed a vaccine for Covid-19 in just three hours.”

There are several reasons that vaccine scientists are skeptical that we will ever see a DNA vaccine for the coronavirus. But speed is not one of them.

“That’s the beauty of these DNA vaccines,” said Wolfgang W. Leitner, the chief of the innate immunity section at the National Institute of Allergy and Infectious Diseases. “They are simple and fast in terms of development.”

Nor are vaccine scientists concerned about the supposed “secret sauce.” In fact, it’s quite the opposite: They are skeptical precisely because the technology behind DNA vaccines has been around for decades and has been applied toward so many infectious diseases — H.I.V., the flu, malaria — yet none of the vaccines have made it to market.

They believe that this approach is capable of producing immunity. Already, DNA vaccines have been licensed for use in pigs, dogs and poultry. But the big if, according to Dr. Dennis M. Klinman, a vaccine scientist who worked at the Food and Drug Administration for 18 years, is whether one will ever be able to generate strong enough an immune response in humans.

Step 2: A series of zaps to ‘steer the DNA’

Even though Ms. Wiley had read the packet on the science of it all, the next step felt like entering uncharted territory.

Shortly after the initial injection, a nurse handed Dr. Ervin a device resembling an electric toothbrush. He pressed the head — which contains three tiny needles instead of bristles — over the raised skin on her arm, where she’d just had a shot. Then he zapped her.

“It was not painful, but it’s unlike anything I’ve ever experienced,” Ms. Wiley said.

The carefully calibrated electrical pulses “basically steer the DNA” into the cells by briefly opening up pores in their membrane, according to [Dr. David B. Weiner (born 1955)], the director of the vaccine and immunotherapy center at the Wistar Institute and an adviser to Inovio.

Although it may sound fantastical, the technology, called electroporation, dates to the 1980s, when a similar approach was first used to make transgenic plants, according to Dr. Leitner.

Phase 1 trials are focused on safety. As a whole, DNA vaccines are known to be very safe, Dr. Klinman has written. Early fears — that they might change a person’s DNA, for example — were proved unfounded long ago.

But there is still no way to know how subjects will respond to the new formula or how the new approach to administering the vaccine will go over. When Dr. Ervin used a different electrical pulse system in an Ebola DNA vaccine trial in 2018, “Boom! They were ready to jump off the table,” he said, adding that he wished he could have paid the subjects extra. (Dr. Ervin runs trials for many biotech companies and is not involved in deciding dosages or implementation methods. His job is to follow the company’s instructions and report back, he said.)

Step 3: Wait for side effects

Ms. Wiley spent the next couple of hours after her injection watching “The King’s Speech” as researchers monitored her for an adverse response. But she felt only relief at being useful in some way.

“I’m not a health care worker; I’m not an essential worker,” she said. “But I’m healthy, so I can do this.”

Soon her sister Ellie Lilly, 46, a seventh-grade history teacher in Lee’s Summit, Mo., had enrolled as well.

Throughout a Phase 1 trial, the newest subjects receive larger doses than participants who started earlier. Ms. Lilly, who entered the trial as Subject 14 four days after her sister, learned that she would be receiving twice as many shots and zaps. Still, the pulses didn’t hurt. “It just feels strange,” she said.

By the time Ms. Lilly got home she felt exhausted and a little nauseous, she said. She told a nurse who called to check in that she wasn’t sure if that was a function of the vaccine or an emotional day. Either way, she felt well enough the following day that her husband wanted to enroll. (He was rejected.)

Four weeks after their first injections, the sisters returned for their second and final doses.

Step 4: Wait to see if it’s deemed safe, and whether it actually did anything

The first hint of whether anyone in the trial developed the coveted antibodies, which would suggest that the vaccine might be helping the immune system, won’t come until Inovio releases that data later this month. That report will include findings from both the Kansas City trial and a simultaneous trial of 20 volunteers in Pennsylvania. This data will influence whether the vaccine dies in the first stage, as most vaccines do, or whether it moves on.

The Phase 1 trial has already been expanded to include older patients at a third location. If everything goes as hoped, the F.D.A. has granted the company permission to start testing effectiveness in the community, according to Inovio.

At that point, researchers would inject thousands of people with the vaccine and thousands more with a placebo. No one would be intentionally exposed to the coronavirus, but by studying rates of infection of the two groups, the researchers could draw conclusions about the effectiveness of the vaccine.

The sisters are rooting for the Inovio vaccine. But, “even if it doesn’t work, we’re still a piece of the research,” Ms. Lilly said.

Ms. Lilly knows that the chances are low that her two experimental doses will protect her, but she can’t help hoping. Come fall, she is headed back to the classroom, where it feels inevitable that sooner or later, she too will be exposed to this tiny but powerful virus.

[Dr. David B. Weiner (born 1955)] is known in scientific circles as “the father of DNA vaccines.” The tag pays homage to his pioneering work over 30 years, but it’s also a reminder that his baby is still aborning.

Not a single human DNA vaccine has made it to market anywhere in the world, and the technology is still rapidly evolving.

The pandemic may be the moment of truth. Genetic code vaccines — built with DNA or RNA — are strong front-runners in the global race to develop an immunization against the coronavirus that has claimed nearly half a million lives worldwide since it emerged in China seven months ago.

[Inovio Pharmaceuticals, Incorporated] — the Plymouth Meeting biotech that Weiner cofounded, advises, and has financial interests in — was recently dissed as “under-the-radar” in industry press. But in March, the company’s DNA vaccine for the coronavirus was featured on TV’s 60 Minutes. And last week, the company snagged a $71 million government contract to manufacture the skin-zapping device that is part of its vaccine platform.

Within days, Inovio says, it will announce results of the first small human trial of its coronavirus vaccine, “INO-4800.” Initial testing focuses on safety, but that shouldn’t be a problem, based on Inovio’s other experimental DNA vaccines.

The big question is whether the shots generated signs of a potent immune response. Feeble responses — too wimpy to protect against infection — have been the Achilles’ heel of DNA vaccines.

[Dr. David B. Weiner (born 1955)], 63, is acutely aware that getting a vaccine approved is about managing expectations, cultivating good press, and raising money — as well as solid science. He said that the vaccine race is against the virus, not rival developers. That multiple vaccines using varying strategies are needed. And that perfect is the enemy of the good.

“I think we should set our expectations low,” he said. “I really think we’re most likely to have several vaccines, and that they will lower disease severity and prevent some infections. It doesn’t have to be 100% effective to have enormous value for the world.”

Fast-tracked

It normally takes a decade or two to get a vaccine from concept to clinic, yet the aim is to start immunizing people against the new coronavirus, SARS-CoV-2, by next summer. More than 120 vaccine candidates using five different strategies are advancing at a breakneck pace, aided by billions of dollars from governments and philanthropies such as the Gates Foundation.

Among the developers already conducting human testing are four with RNA platforms: Moderna, Pfizer, CureVac, and Imperial College London. [Inovio Pharmaceuticals, Incorporated] is the only front-runner with a DNA-based vaccine.

All vaccine approaches involve teaching the immune system to recognize a virus’ unique proteins, or antigens. If the real microbe tries to invade — and viruses have to hijack living cells to replicate — immune cells are primed to attack.

Tried-and-true vaccine technologies involve growing a weakened or inactivated virus in eggs or animal cells, then extracting and purifying the desired antigens. It’s an arduous, time-consuming, costly process.

In the early 1990s, [Dr. David B. Weiner (born 1955)] and some others had an idea: Instead of injecting the antigen, why not inject the viral gene that carries instructions — DNA — for making it? DNA would transfer the instructions to RNA in the cell’s molecular machinery, which would then produce the antigen to ward off infection.

The beauty of the approach was obvious from the beginning. DNA is a sequence of chemicals, called nucleic acids, that can be rapidly synthesized and fused together in the lab.

Consider that after Chinese researchers published the coronavirus’ entire genetic code in January, Inovio scientists “printed” their vaccine in a matter of hours with a DNA synthesizer. Like almost all developers, they used the code for the “spike” protein, which makes the stud-like projections that the coronavirus uses to latch onto and sneak into cells. But while the advantages of using DNA were clear, so were the challenges.

Nature instructs

Weiner was a professor of medicine and a researcher at the University of Pennsylvania in the 1990s when he pioneered the technology for delivering the DNA into cells.

Decades earlier, researchers had discovered that bacteria carried strange little loops of DNA that were separate from their chromosomal DNA and could replicate independently. Some of these “plasmids” were found to help bacteria resist antibiotics.

Weiner’s lab synthesized and equipped plasmids to carry viral antigen genes into human cells.

“We look for nature to teach us what to do,” said Weiner, who is now emeritus at Penn and vice president of Wistar Institute, which is collaborating on Inovio’s vaccine.

In 1997, Weiner’s team reported a breakthrough: Their novel vaccine had protected two chimpanzees from the virus that causes AIDS. (Fun fact: Weiner and his lab had a cameo in Philadelphia, the 1993 movie about HIV/AIDS and homophobia that earned Tom Hanks an Oscar.)

In humans, however, DNA vaccines simply weren’t very effective. At the injection site, uptake of plasmids by skin and muscle cells was nominal and unpredictable. When the cells produced antigen, it triggered a tepid response by the first line of immune defense — namely, antibodies. But few plasmids found their way into “antigen-presenting cells,” which are essential for activating the more powerful second line of defense — T cells. “Killer” T cells can destroy virus inside as well as outside of cells, and “memory“ T cells remember the invader to prevent future infections.

By 1999, when Weiner wrote about DNA vaccines in Scientific American, the best he could say was, “Preliminary findings hint that useful immune responses can be achieved.”

He soldiered on with a team that included graduate student Joseph Kim, now president, CEO, and cofounder of Inovio.

“A lot of big boys and girls left the field,” Kim said, referring to giant pharma companies that abandoned DNA vaccine research. “One who persisted, by conviction or stubbornness or both, was [Dr. David B. Weiner (born 1955)].”

Among the “optimization” measures: The plasmids were engineered to carry additional genes that made cells produce natural immune-boosting substances, including one that stimulated proliferation of the important antigen-presenting cells. To get better uptake of the plasmids, the vaccine was delivered along with electrical charges that briefly opened pores in cell membranes near the injection site.

Manufacture of that handheld “electroporation” device — a proprietary, battery-operated gizmo now named Cellectra — will be scaled up using $71 million from the U.S Department of Defense.

Dark horse or front-runner

RNA vaccine technology, which is also about 30 years old, has a different set of pros and cons. Messenger RNA doesn’t need a plasmid because it doesn’t have to get into the cell’s nuclear DNA to work. But single-stranded RNA is far less stable than double-stranded DNA. Enzymes in the body can quickly degrade RNA, which cuts antigen production. The vaccine has to be kept refrigerated or frozen.

The instability problem is like “buying fruit that spoils in a few minutes,” said [Dr. David B. Weiner (born 1955)], adding that he is biased.

Inovio can be seen as a dark horse in the vaccine race — or an odds-on favorite.

None of its prospects has crossed the finish line. Its Ebola and Zika vaccines had to be abandoned because as the outbreaks waned, so did funding and the number of potential clinical trial subjects.

On the other hand, Inovio has 15 vaccines in clinical testing for cancer as well as infectious diseases. The company is expanding human testing of its vaccine for Middle East Respiratory Syndrome (MERS) — caused by another coronavirus — because it generated strong antibody and T-cell responses in most participants in an initial trial.

“It’s going to take many technologies crossing the finish line to make an impact in the face of SARS-CoV-2,” Weiner said, “and we hope our technology can be part of the solution.”

As the deadly new virus spread globally, Inovio Pharmaceuticals, a small biotech company in Pennsylvania, rushed to develop a vaccine. After announcing promising early results, Inovio’s stock soared more than 1,000 percent. Riding the momentum, the company sold more shares to the public.

That was 2009, when H1N1, better known as swine flu, was stoking fears of a devastating pandemic. In the years since, Inovio has announced encouraging news about its work on vaccines for malaria, the Zika virus and even a “cancer vaccine.” [ see https://ir.inovio.com/news-releases/news-releases-details/2013/Inovio-Pharmaceuticals-Potent-hTERT-DNA-Cancer-Vaccine-Shows-Potential-to-Reduce-Tumors-and-Prevent-Tumor-Recurrence/default.aspx ] The upbeat declarations have caused the company’s stock price to leap, enriching investors and senior executives.

There’s only one catch: Inovio has never actually brought a vaccine to market.

Now, with a new pandemic raging, Inovio is working on a new vaccine: for the novel coronavirus. A flurry of positive news releases about its funding and preliminary results have sent Inovio’s shares up by as much as 963 percent — and helped the company attract money from the government and investors. At the same time, Inovio insiders have sold stock.

But some scientists and financial analysts question the viability of Inovio’s technology. While there are some early signs of promise with the company’s vaccine, Inovio has only released bare-bones data from the first phase of clinical trials. It is locked in a legal battle with a key manufacturing partner that claims Inovio stole its technology.

Shareholders have sued Inovio, claiming it has exaggerated its progress on a coronavirus vaccine to inflate its stock price. Adding to the challenges, Inovio’s potential vaccine will have to be administered by a gadget — it resembles an electric nose-hair trimmer and is called the Cellectra — that would direct genetic material into millions of patients.

And while the company has said that it is part of Operation Warp Speed — the flagship federal effort to quickly produce treatments and vaccines for the coronavirus — Inovio is not on the list of companies selected to receive financial support to mass-produce vaccines.

“The absence of that funding, coupled with their ongoing litigation, coupled with the need to scale a device, coupled with the absence of complete Phase 1 data, makes people skeptical,” said Stephen Willey, an analyst at Stifel, an investment firm.

As it tries to defuse the coronavirus crisis, the Trump administration is wagering, in part, on companies — like Modernaand Novavax — with spotty track records and penchants for self-promotion. In June, Inovio received $71 million from the Department of Defense to manufacture its battery-operated Cellectras.

Some medical experts worry that taxpayer backing for unproven companies could erode the public’s already tenuous faith in vaccines.

“If you dry up trust, you’ll have almost a self-defeating proposition with vaccine uptake,” said Arthur L. Caplan, a bioethicist at the New York University School of Medicine. “The more you’re hype and less you’re reality, the more you are taking funds away from things that are cheaper, closer or both,” he added.

Inovio could provide an update on its progress with the vaccine when it releases its second-quarter financial results on Monday.

Developing vaccines is hard. In addition to coming up with an effective formula and the funding to produce it, drug makers need to navigate an obstacle course of government safety checks and rigorous scientific review on a fast enough timeline to stay competitive. The fact that a company like Inovio has never brought a vaccine to market is not necessarily an indictment of its underlying approach to creating vaccines. Otherwise, scientists say, the world would never have technological breakthroughs.

Inovio’s specialty is attempting to develop DNA-based vaccines, which use a virus’s own genes to provoke an immune response. But the company’s decade of attempts have not borne fruit.

In fact, no DNA-based vaccine has ever made it to market. While some have produced encouraging results in small animals, they have not proven effective in humans — against the coronavirus or any other disease.

Nonetheless, the scientific community continues to believe the technology is promising in part because such gene-based vaccines can be designed quickly. Companies in Korea, India and Japan are pursuing similar DNA-based coronavirus vaccines.

Inovio’s chief executive, J. Joseph Kim, has said that when the DNA sequence of the coronavirus became public in January, the company was able to immediately engineer a vaccine. Later that month, Inovio secured a $9 million grant from the Coalition of Epidemic Preparedness Innovations, a leading funder of vaccine research.

In March, Dr. Kim — an immunologist who became chief executive of Inovio in 2009 — was invited to participate in a meeting in the White House’s Cabinet Room with President Trump and pharmaceutical executives.

At the public meeting, Dr. Kim described Inovio as “the leader in coronavirus vaccine development in the world,” adding that it had its own manufacturing capabilities.

Mr. Kim said that, thanks to “our very innovative, 21st-century platform,” Inovio had been “able to fully construct our vaccine within three hours.” All the company needed now, he told Mr. Trump, was the federal government’s support to help scale up manufacturing.

Inovio’s stock shot up 220 percent over the coming days. Its market value has gone from less than $500 million at the start of the year to more than $3 billion today.

Shortly after the White House meeting, Inovio announced that it had received a $5 million grant from the Bill and Melinda Gates Foundation. The money would help Inovio test the Cellectra. The devices use electrical pulses to direct DNA into patients’ cells — a technique that experts said is grounded in legitimate science.

Some investors, though, had grown skeptical.

On March 9, Andrew Left of Citron Capital, which is shorting Inovio’s stock and stands to profit if it declines, began publicly questioning [ see below ... ] Inovio’s approach to devising a coronavirus vaccine and accusing it of engaging in “serial stock promotion.” He later issued a report [see https://citronresearch.com/wp-content/uploads/2020/04/Inovio-Pharmaceuticals-Bad-Blood.pdf ]  comparing the company to Theranos, the disgraced blood-testing company, and cataloging Inovio’s history of promoting and then failing to produce vaccines.

Inovio’s stock price plunged 66 percent, though it would soon soar to new heights thanks to optimism about its potential vaccine.

Days later, shareholders sued Inovio in federal court in Pennsylvania. Citing Dr. Kim’s remarks at the White House and earlier comments he made on Fox Business Network about having created a vaccine, the suit claimed that the company had “capitalized on widespread Covid-19 fears by falsely claiming that Inovio had developed a vaccine.” In April, another group of shareholders filed a separate suit [see https://www.dandodiary.com/wp-content/uploads/sites/893/2020/04/Inovio-derivative-complaint.pdf ] in the same court, accusing Dr. Kim and Inovio’s board of mismanagement and unjustly enriching themselves, among other things.

Inovio has disputed Mr. Left’s critiques, but the company publicly clarified that it had developed a vaccine construct — essentially a road map — not an actual vaccine. Inovio has not publicly responded to the pending shareholder lawsuits.

Over the past 10 years, insiders at Inovio have sold more than $25 million in stock, according to the financial data provider Equilar. Last year, Dr. Kim was forced to sell about half his Inovio shares — causing the stock price to drop by more than a third — after he used his shares as collateral to borrow money and was caught in a so-called margin call, requiring him to immediately repay his loan.

This year, following steep run-ups in Inovio’s stock price, insiders have sold $3.8 million in shares. (Earlier this year, Inovio banned executives from “engaging in short-term or speculative transactions in the company’s securities, including pledging and purchasing company securities on margin.”)

Hoping to raise money to fund its vaccine efforts, Inovio said this year that it planned to sell some $150 million in new stock to investors.

In April, Inovio began trials of its potential vaccine, testing it on 36 people. (A volunteer in the trial said that getting zapped with the Cellectra didn’t hurt. “It just feels strange,” she said.)

On the last day of June, Inovio reported encouraging results in the 36-person trial. Inovio said its vaccine was “generally safe and well-tolerated” and generated an immune response.

But the company did not disclose any data about the magnitude of that response. Scientists said that made it impossible to gauge whether the vaccine would protect anyone.

Jeff Richardson, an Inovio spokesman, said the company would release more data soon.

When it announced the study results, Inovio also claimed that its vaccine had been “selected for the U.S. Government’s Operation Warp Speed.” But Inovio was not given federal funding to produce vaccines. Instead, its vaccine candidate had been chosen for inclusion in a preliminary study on rhesus macaque monkeys that had been organized by Warp Speed. (Vaxart, another company participating in the monkey trial, similarly claimed to have been selected for Warp Speed, drawing criticism from the Department of Health and Human Services.)

Asked about Inovio’s claim to be part of Warp Speed, Mr. Richardson said: “It depends on what you call Warp Speed.” He declined further comment.

At the White House, Dr. Kim had talked up Inovio’s manufacturing capabilities. While the company does manufacture its Cellectra, it has relied on another company, VGX International, to manufacture its vaccine candidate.

Now, Inovio and VGX are in a legal fight. In June, Inovio sued, claiming that VGX was refusing to share technology needed to produce the Inovio vaccine with other companies and was endangering public health. The case, along with a countersuit by VGX, is pending in state court in Pennsylvania.

In court filings, VGX accused Inovio of stealing trade secrets and challenged its claim that there is a public interest in Inovio’s work.

“Although the Covid-19 pandemic is horrible, Inovio is unlikely to win the race for the vaccine,” VGX lawyers wrote. Despite Inovio’s years of work, “it has never developed an F.D.A.-approved product.”

Inovio will take a trip to sunny Brazil to run a phase 3 trial testing its COVID-19 vaccine, months after the U.S. turned off the lights for the late-stage study.

The Plymouth Meeting, Pennsylvania-based company received authorization from Brazilian health officials to run the phase 3 portion of the phase 2/3 trial, called Innovate, which will test the company’s vaccine INO-4800, according to a Thursday statement. 

The news breathed a some life back into Inovio’s shares, which took a major hit after U.S. officials stopped funding for the vaccine candidate back in April. Inovio shares were trading up more than 7% at $9.07 as the markets opened Thursday.

Inovio has run into plenty of trouble with its DNA vaccine candidate, falling well behind chief competitors Pfizer-BioNTech and Moderna. U.S. officials pulled the plug on funding for the biotech as inoculations picked up around the country. Also, in September, the FDA placed Inovio's phase 2/3 on a partial clinical hold. 

But Inovio has pressed on, promising a shelf-stable vaccine that could keep at room temperature for up to a year. This would be an improvement over the leading authorized mRNA shots, which have cold storage requirements. Many countries lag behind the U.S. in administering vaccines, so Inovio could find a market if they can get the vaccine through clinical research.

"With many countries in the world experiencing low vaccination rates and seeing an increase in infections, we feel the urgency to advance INO-4800 globally,” said Inovio President and CEO [Dr. Jong Joseph Kim (born 1969)] in the statement. 

The phase 3 study will examine the efficacy of two INO-4800 doses administered one month apart in men and women 18 years old and up. The primary endpoint will be virologically confirmed COVID-19. Inovio will conduct the trial in Latin America, Asia and Africa.

Inovio’s phase 2 study was funded by the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and other agencies. The vaccine also received early research funding from the Bill & Melinda Gates Foundation.

INO-4800 was found to be well-tolerated and produced an immune response in adults during earlier studies.

The biotech is also working with Sinovac Biotechnology on two clinical trials testing boosting with INO-4800 and Sinovac’s World Health Organization-approved CoronaVac.

Meanwhile, Pfizer is expecting a whopping $33.5 billion in sales for its now-approved COVID-19 shot, named Comirnaty.

Shares of [Inovio Pharmaceuticals, Incorporated] are down more than 22% in premarket trading after the company announced a leadership change at the helm and the discontinuation of a Phase III COVID-19 vaccine study.

Pennsylvania-based Inovio announced Tuesday that Chief Executive Officer [Dr. Jong Joseph Kim (born 1969)] has resigned from his position, as well as from his role as president and a member of the company board of directors. [Jacqueline Elizabeth Shea, Ph.D. (born 1965)], who has served as the chief operating officer of [Inovio Pharmaceuticals, Incorporated] since 2019, will take over the company's reins in his stead. 

Before coming to Inovio, Shea served as COO and later as CEO of tuberculosis-focused  [AERAS Global TB Vaccine Foundation], a not-for-profit drug development organization. She also previously held leadership roles at Emergent BioSolutions.

Not only has the company made a change in the C-suite, but in its quarterly financial report on Tuesday, Inovio announced plans to discontinue its Phase III Innovate trial in order to prioritize its heterologous booster strategy for COVID-19. The late-stage study was assessing INO-4800, the company's DNA vaccine candidate for COVID-19. The vaccine candidate is an intradermally-injected DNA plasmid vaccine designed to control the virological spread of COVID-19. 

In its announcement, changes in infection rates across the globe indicate the company will need to increase the trial size and cost of the INNOVATE study. In contrast, the heterologous booster market offers greater opportunities due to the endemic phase of COVID-19. So, instead of assessing INO-4800 as a two-dose vaccine, Inovio and its developmental partner Advaccine will examine the drug candidate as a heterologous booster to an inactivated COVID-19 vaccine. 

Earlier clinical data from a study conducted by Advaccine showed positive T cell immune response. In that study, interim immunogenicity data showed that using INO-4800 as a booster after six months resulted in a 6.3-fold increase in T cell immune response. 

In a separate Advaccine study examining a third dose of a COVID-19 vaccine, the cellular response increased by 1.7-fold. The highest booster effect of INO-4800 was observed with a 2 mg dose of INO-4800 delivered 6 months after a primary series with an inactivated vaccine.

With this understanding, Inovio said INO-4800 has the potential to play an important role in reducing the incidence of severe COVID-19 cases, particularly of viral mutations. The company is discussing this option with regulatory agencies across the globe.

New CEO Shea said the company believes in the potential of its DNA medicines and vaccines. In order to achieve the goals of being able to combat infectious diseases and other indications, Inovio had to "strategically prioritize" its resources to "capitalize on its demonstrated ability to generate functional T-cell and antibody immune responses."

As Inovio moves forward, the company intends to expand its partnership with Advaccine beyond INO-4800 to include heterologous boosters and vaccine candidates covering future COVID-19 variants. The expanded partnership will allow both companies to share data, leverage Advaccine's multiple manufacturing sites in China, and access opportunities globally.

Additionally, Inovio announced a change in plans regarding its therapy for HPV-associated cervical high-grade squamous intraepithelial lesions, VGX-3100. Following input from the U.S. Food and Drug Administration, Inovio will shift its focus to a biomarker study after the regulatory agency said data from the Phase III REVEAL2 study will not be sufficient for approval. 

The FDA recommended that data from Reveal2 could be used as an exploratory study to evaluate a biomarker-selected population. Then, Inovio can conduct one or two additional trials in the biomarker-positive population in order to provide enough evidence to support the approval of a marketing application.

In response, Inovio will amend the Reveal2 trial to revise the primary analysis population from the all-comers population to the biomarker-positive population. The change in regulatory guidance, though means that Inovio no longer anticipates filing a Biologics License Application for VGX-3100 in 2023.