INO-4800 COVID-19 Vaccine Candidate: Dark Horse Contender?

Jun 28, 2020 | COVID-19, INO-4800, Inovio Pharmaceuticals, Investigator Watch, News, Popular Posts, Vaccine

INO-4800 COVID-19 Vaccine Candidate: Dark Horse Contender?

Inovio Pharmaceuticals was co-founded by an individual known in scientific circles as “the father of DNA vaccines.” David Weiner, head of Wistar Institute’s Weiner Laboratory, has spent decades working toward this moment in history. Although Inovio’s INO-4800 hasn’t been considered a primary vaccine contender, the company was featured on 60 Minutes and recently, the firm secured $71 million in government funds to manufacture the electro-device that is part of its COVID-19 vaccine platform. To date, not a single human DNA vaccine has been commercialized worldwide.   

Leading the Pack?

Industry, media, purported experts, and some investors are leaning toward Moderna (mRNA-1273), which is preparing for their Phase 3 clinical trial, however University of Oxford partnered with AstraZeneca to take the vaccine to Phase 3 and hopefully commercialization. The U.S. government place a $483 million bet on Moderna and a $1 billion on the AstraZeneca and Oxford partnership. University of Oxford and AstraZeneca have progressed AZD1222 to the critical Phase 2/3 clinical trial stage involving a 10, 260 participant study in the UK. CanSino Biologics from China has inked a deal with the Canadian government to supply that country with vaccine product should it be approved. They commenced a Phase 1/2 clinical trial in Halifax Canada which started May, 2020 and are planning a Phase 3 trial in China despite results in a Phase I vaccine study that left some question marks. Of course, two other mRNA-based vaccines include BioNTech and Curevac while China has a few leading candidates.

An Inside Track?

Recently, Marie McCullough, writing for Allentown, PA’s The Morning Call, reported on Pennsylvania’s Inovio Pharmaceuticals and their specific race to develop a COVID-19 vaccine.  Vaccines typically takes over a decade, if not two decades to progress a vaccine from lab to regulatory approval, manufacturing and on to the clinic. Over 120 vaccine developers, from commercial biotech to non-profits and university developers, vie for competitive position in the intense race for the critically important vaccine. The press seems to have identified a few top contenders precluding INO-4800.

A Complex Process and a New Answer?

Developing a successful vaccine centers on the product’s ability to train the immune system to not only recognize the virus’ unique antigens (proteins) hence when the virus actually attacks the immune cells are ready. Established approaches involve the growing of a weakened or inactivated virus in eggs or animal cells, reports The Morning Call.  Weiner and others by the 1990s sought to bypass this lengthy and cumbersome process by rather injecting the viral gene possessing the DNA for making the antigen to fend off infection.

The DNA Journey

Although the DNA-based vaccine exhibits some advantages, it also poses challenges. Weiner spent decades in his lab pioneering the technology for delivering the DNA into cells. By 1997, he and his research team had a breakthrough when their novel AIDS vaccine actually protected two chimpanzees from the virus that causes AIDS. But in humans, the DNA vaccines weren’t effective. 

The uptake of plasmids by skin and muscle cells was not robust and unfortunately unpredictable reported Marie McCullough. Hence as the cells produced antigens the body’s response was weak by the immune response.  Some of the plasmids were able to enter into “antigen-presenting cells” which are key for triggering T-cells, the second line of defense.  

These “Killer T-cells” can actually terminate virus’ inside as well as outside of cells while a form of memory is incorporated to remember the pathogen in anticipation of future invasions. By 1999, Ms. McCullough reports that Weiner’s incredibly promising science could at best produce the following sentiment: “Preliminary findings hint that useful immune responses can be achieved.”

The Joseph Kim Partnership

Later on, a graduate student named Joseph Kim joined the Wiener DNA-based vaccine research team (Kim is now CEO of Inovio). Kim touts that “A lot of big boys and girls left the field,” declaring, “One who persisted, by conviction or stubbornness or both, was Dave Weiner.” 


The advanced messenger RNA-based ventures such as Moderna, CureVac and BioNTech encapsulate on RNA based technology, which is now three decades old and raises another set of benefits and risks. For example, RNA precludes a dependency on a plasmid as it doesn’t require entry into the cell’s nuclear DNA. However, far less stable than double-stranded DNA, RNA is single-stranded and hence the body’s enzymes can rapidly degrade RNA, hence cutting antigen production. Moreover, there are considerable maintenance requirements such as refrigeration and overall this leads to an instability issue akin to “buying fruit that spoils in a few minutes,” reports Weiner.

A Dark Horse or Odds-on Favorite?

None of Inovio Pharmaceuticals products have ever been commercialized—not its Ebola nor its Zika vaccine investigational products. These initiatives died as the outbreaks faded along with funding and clinical trial participants. However, the company has developed a healthy pipeline of vaccines for cancer and infectious diseases. Weiner believes that a combating COVID-19 requires a diversified response involving many technologies, saying, “we hope our technology can be part of the solution.”

The Financials

The company’s stock price is high at $29.98 per share, something not seen in 20 years. Now with a $4.94 billion market capitalization,  the company still loses about $101 million with total cash position of about $270 million. The company has a healthy vaccine pipeline but the COVID-19 vaccine is obviously a game changer, should it progress in clinical trials.


  1. ian

    it is true.
    current ebola vaccine in Africa is based on virus vector from canada original from german.

    RNA OR DNA vaccine still have long journey.
    the stock prices flying is the greed.

    • TrialSite

      Dear Ian,
      We can’t disagree that there is a strong case of Greed out there!
      Thanks for the visit. We are grateful.

  2. Walt

    Interesting that the CanSino vaccine produced neutralizing antibodies and had positive results for all study participants. Some outside western experts maybe had hoped for more so cast a pall on the study, while still boosting Moderna and Oxford. This is really funny considering CanSino is the only vaccine who has actually published their results. So it seems do not publish and you remain the darling of the experts, publish and you get trashed. Maybe it is not a Western solution? Remdesivir does nothing but was spun by the experts.
    This whole process of vetting is totally antiquated for today’s Information Age and needs to be fixed. The information dissemination cannot remain in the hands of those who are invested in the outcome. Keep up the good work TrialSite.