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Many public health authorities believe that DNA medicines may be the best modern approach to addressing potential infectious disease pandemics due to their rapid design and manufacture.
INOVIO has seven programs in clinical studies to address infectious diseases, including COVID-19, HIV, Zika, Ebola, Lassa fever, and MERS (both COVID-19 and MERS are caused by coronaviruses). These programs are all externally funded by global public health organizations, including the Coalition for Epidemic Preparedness Innovations (CEPI), the National Institutes of Health, and the Bill & Melinda Gates Foundation. INOVIO also has the first-ever DNA-encoded monoclonal antibody (dMAb™), which is in clinical trials targeting the Zika virus.
Since its discovery in 1981, HIV, the virus which causes AIDS, has killed more than 35 million people.1 Globally, 37.9 million people were living with HIV at the end of 2018. The WHO African region remains the most severely affected with nearly 1 in 25 adults living with HIV.2
Effective vaccines have been actively pursued for over 30 years, without significant success. HIV represents one of the most confounding targets in medicine. The virus’s high mutagenicity (ability to mutate) has made effective vaccine development very challenging. Its outer envelope, swathed in sugar molecules, is difficult to attack, and HIV strikes the very cells that the immune system launches to thwart such an infection.3 Although several drugs (anti-retrovirals) are available to treat the patients once they are infected, vaccines and DNA medicines are necessary to stop the spread of disease and perhaps reduce the need for anti-retroviral treatment.4
Advancements on the Horizon for HIV
INOVIO has PENNVAX®-GP in development to prevent and treat HIV strains present in Africa, Asia, Europe, and North America. It has been optimized to target two env antigens, as well as gag and pol antigens. This comprehensive targeting gives PENNVAX-GP the potential to provide global coverage against HIV-1 subtypes. Using a $25 million contract from the NIH, PENNVAX-GP entered into a Phase 1 clinical study in 2015. In addition, INOVIO and academic collaborators, including University of Pennsylvania, University of Massachusetts, Emory University, and Duke University, received a $16 million grant from the NIAID to test various approaches using PENNVAX-GP in preclinical models.
Del Rio C. The global HIV epidemic: What the pathologist needs to know. Semin Diagn Pathol. 2017;34(4):314-317. doi:10.1053/j.semdp.2017.05.
World Health Organization (WHO). Global Health Observatory (GHO) data – HIV/AIDS. Available at: who.int. Accessed April 3, 2020.
Cai H, Orwenyo J, Giddens, JP, et al. Synthetic Three-Component HIV-1 V3 Glycopeptide Immunogens Induce Glycan-Dependent Antibody Responses. Cell Chemical Biology. 2017;24(12):1513-1522. Available at: doi.org.
HIV.gov (HHS). HIV Vaccines. Available at: hiv.gov. Accessed April 3, 2020.
The Ebola virus has been described as one of the most virulent viral diseases, with lethality rates up to 90%. Ebola can spread through human-to-human transmission by direct contact with the blood, secretions, organs or bodily fluids of an infected individual and with surfaces or materials that contain the contaminated fluids of an infected person, such as bedding and clothing. It is capable of causing death within two to twenty-one days of exposure.1
Advancements on the Horizon for Ebola
INOVIO is taking a multi-faceted approach to develop products to prevent and treat Ebola infection. These programs include development and early clinical testing of:
In March 2019, Phase 1 clinical data of Ebola vaccine candidate INO-4201 was published in The Journal of Infectious Diseases, in the article entitled, “Intradermal SynCon® Ebola GP DNA Vaccine is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers.” The study, which is being fully funded by U.S. Defense Advanced Research Projects Agency (DARPA), further supports the advancement of the intradermal delivery platform for emerging infectious diseases.
World Health Organization (WHO). Ebola virus disease. Available at: who.int. Accessed April 3, 2020.
Middle East Respiratory Syndrome Facts (MERS) is a viral respiratory illness and all cases are linked to the Arabian Peninsula. MERS appears to have been transmitted from an animal reservoir to humans but human to human transmission has been confirmed. This communicable virus has not been shown to spread in a sustained way in communities, but rapid spread in the nosocomial setting, such as emergency rooms and/or hospitals without adherence to state-of-the-art infection control practices, can result in outbreaks with many cases, including superspreading events.1 Like the severe acute respiratory syndrome (SARS) outbreak in 2003, which made approximately 8,000 people ill and was fatal in nearly 10% of those cases,2 MERS is caused by a coronavirus and appears to cause a severe lung infection.1 Despite the continuing threat of MERS outbreaks, there are no licensed vaccines or treatments for MERS.1
Advancements on the Horizon for MERS
In November 2013, INOVIO announced that preclinical testing of our MERS DNA vaccine candidate, INO-4700 (formerly known as GLS-5300), had induced robust and durable immune responses, demonstrating the potential for such a vaccine to prevent and treat this deadly virus. DNA vaccine constructs targeting multiple MERS antigens were designed with the goal to universally protect against multiple strains of MERS, which has been shown to have diverse genetic variants.
INO-4700 is currently in Phase 1/2a development for the treatment and prevention of MERS. INOVIO and GeneOne Life Science are co-developing INO-4700 in collaboration with the Walter Reed Army Institute of Research.
First identified in the late 1940s in Uganda, Zika virus subsequently spread to equatorial Asia in 1969 and then rapidly spread through the Pacific, and still later, in the 2014-2016 period, to and through South America, Central America and the Caribbean. In the end of that period, Zika virus emerged in two portions of the continental United States (extreme Southeastern Florida and extreme South Texas).1,2 Zika virus is a flavivirus, a family of viruses including yellow fever, dengue, and West Nile virus, which are introduced to people through mosquito bites. Because the Aedes species of mosquitoes that spread Zika virus are found in much of the world, there is concern that the virus will spread to new countries and cause additional outbreaks.1,3 Currently the U.S. CDC lists at least 94 countries and territories as having risk of Zika virus infection and notes that the virus is still a threat.4 No vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials.
Advancements on the Horizon for Zika
INOVIO has two DNA medicines in development for Zika: INO-4700 and INO-A002. INOVIO and GeneOne Life Science are co-developing INO-4700 (formerly known as GLS-5700) for the prevention and treatment of Zika virus infection with academic collaborators in the United States and Canada. INO-4700 is in Phase 2 clinical trials.
INO-A002 is the first DNA-encoded monoclonal antibody candidate being developed for preventing or treating Zika virus infection. INOVIO expects to report results in 2020 from its first-in-human trial from a Phase 1 dose-escalation trial with full funding from the Bill & Melinda Gates Foundation to assess safety and tolerability and expression of antibodies produced by the dMAb™ plasmid. Using direct local delivery into the body, the dMAb plasmids instruct the body’s cells to become a customized patient-specific factory that manufactures its own therapeutic monoclonal antibodies, enabling a major leap in antibody technology. With its plasmid design and in-patient production, dMAb products represent a disruptive and innovative entrant to this important class of therapies.
World Health Organization (WHO). Zika virus. Available at: who.int. Accessed April 3, 2020.
Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D. An update on Zika virus infection. Lancet. 2017 Nov 4;390(10107):2099-2109.
Centers for Disease Control and Prevention (CDC). Zika Virus – Clinical Evaluation & Disease (for healthcare professionals). Available at: cdc.gov. Accessed April 3, 2020.
Centers for Disease Control and Prevention (CDC). Zika Travel Information. Available at: cdc.gov. Accessed April 3, 2020.
Discovered in 1969, Lassa fever is an animal-borne acute viral illness. Humans usually become infected with Lassa virus through exposure to food or household items contaminated with urine or feces of infected Mastomys rats. The disease is endemic in the rodent population in parts of West Africa. An estimated 100,000 to 300,000 infections of Lassa fever occur annually, with approximately 5,000 deaths.1
Advancements on the Horizon for Lassa Fever
INOVIO is conducting a Phase 1, first-in-human clinical trial to evaluate INO-4500, a DNA candidate vaccine to prevent infection from the Lassa virus. This trial is the first Lassa fever candidate vaccine to enter the clinic. The INO-4500 program is fully funded through a global partnership with CEPI – the Coalition for Epidemic Preparedness Innovations. INOVIO is also planning to advance INO-4500 to a Phase 1b trial in Africa in 2020.
Centers for Disease Control and Prevention (CDC). Lassa Fever. Available at: cdc.gov. Accessed April 3, 2020.
Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person.1 The virus that causes COVID-19 is a novel coronavirus that was first identified in December 2019.
Advancements on the Horizon for COVID-19
To help in the fight for the coronavirus (SARS-CoV-2) that causes COVID-19, INOVIO created an optimized plasmid in about three hours based on the virus’s genetic sequence. The company began small-scale manufacturing of the DNA vaccine – INO-4800 – in the lab, followed by preclinical testing to assess its safety and immunogenicity. On April 6, less than three months after creating INO-4800, INOVIO announced the U.S. Food and Drug Administration authorized its Investigational New Drug (IND) application and the company began Phase 1 clinical trials in humans.
Centers for Disease Control and Prevention (CDC). 2019 Novel Coronavirus. Available at: cdc.gov. Accessed February 12, 2020.
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