Inovio Pharmaceuticals is at the forefront of developing innovative DNA medicines aimed at treating HPV-related diseases, cancer, and infectious diseases. The company utilizes proprietary technology to create optimized DNA plasmids, which are small circular DNA molecules that function similarly to software, instructing the body’s cells to produce specific proteins that target and combat diseases. Their investigational CELLECTRA® delivery devices are designed to facilitate the efficient entry of these plasmids into cells through electroporation, a process that temporarily opens pores in the cell membrane without the need for chemical adjuvants, lipid nanoparticles, or viral vectors. This method enhances the delivery and effectiveness of their DNA medicines, allowing for localized protein expression and sustained immune responses.

Inovio's SynCon® technology further refines the design of these plasmids using a proprietary algorithm, enabling the creation of candidates that can address a wide range of disease targets. The company is also pioneering next-generation DNA medicine technologies, including DNA-encoded monoclonal antibodies (DMAbs) and DNA-launched nanoparticles (dLNPs). DMAbs allow for the in vivo production of monoclonal antibodies directly within the body, potentially reducing administration frequency and manufacturing costs. Meanwhile, dLNPs combine the benefits of nanoparticle technology with the capabilities of DNA medicines to stimulate robust immune responses. Overall, Inovio's advancements in DNA medicine technology hold significant promise for transforming treatment paradigms and improving patient outcomes.

United States

INOVIO is a biotechnology company committed to powering a new way forward in DNA medicines to save and protect lives worldwide. The company is focused on rapidly bringing to market precisely designed and delivered DNA medicines to potentially treat and protect people from serious and life-threatening diseases associated with HPV, cancer, and infectious diseases.

Cancer

Infectious Diseases

Urogenital Diseases

Inovio Pharmaceuticals

Lung disease

Recurrent respiratory papillomatosis

Respiratory conditions

INO-3107

Anal cancer

High-grade squamous intraepithelial lesion

VGX-3100 is a DNA medicine under Phase 3 investigation for the treatment of HPV-16 and HPV-18 infection and precancerous lesions of the cervix. INOVIO is in open-label Phase 2 clinical trials evaluating its efficacy for treating HPV-related vulvar and anal dysplasia (HSIL). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for precancerous cervical lesions. It works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of precancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical dysplasia (CIN2/3 or HSIL), treatment with VGX-3100 resulted in a statistically significantly greater regression of cervical dysplasia and clearance of HPV-16/18 infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient's own immune system to clear HPV-16 and HPV-18 infection and precancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

VGX-3100 

Glioblastoma

Solid tumor/s

INO-5401 encodes for INOVIO's SynCon® antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.

INO-5401 + Libtayo

Vaccine

INO-4201 is a DNA vaccine targeting Zaire Ebola virus (ZEBOV) glycoprotein (GP), designed to prevent ZEBOV infection. INO-4201 encodes for a synthetic consensus antigen that encompasses ZEBOV genetic variability from various outbreak strains to broaden immune coverage for divergent ZEBOV virus variants.

INO-4201/Ebola Booster (rVSV-ZEBOV)

COVID-19

The Phase 1 trial is the first clinical study to report using synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells. Participants received an intramuscular (IM) injection of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived from&nbsp;AstraZeneca's cilgavimab and tixagevimab) delivered via INOVIO's proprietary CELLECTRA 2000 electroporation (EP) device. This delivery method temporarily increases cell permeability, which is intended to facilitate efficient DNA uptake and enable sustained antibody production.
 
The study is an open-label, single center, dose-escalation trial. Enrollment began in May 2022 and was completed in March 2024. The most common side effects observed were temporary local injection site reactions, such as pain and erythema, associated with the administration of the study product. There were three SAEs all of which were considered unrelated to the study product.

DNA-Encoded Monoclonal Antibodies (DMAbs)

INO-5401 +/- INO-9012

Infectious disease

INO-4800 is INOVIO's DNA vaccine candidate against SARS-CoV-2, the novel coronavirus that causes COVID-19. Composed of an optimized DNA plasmid, INO-4800 is delivered directly into cells in the body via a proprietary smart device to produce a robust and tolerable immune response. INO-4800 is the only nucleic-acid based vaccine that is stable at room temperature for more than a year, at 37o C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage – all of which are important considerations when preparing for mass immunizations. <a href="https://ir.inovio.com/news-releases/news-releases-details/2021/INOVIOs-COVID-19-Vaccine-Candidate-INO-4800-Provides-Broad-Cross-reactive-Immune-Responses-In-Humans-Against-Variants-of-Concern/default.aspx">SOURCE</a>
 
INO-4800 is a plasmid DNA vaccine that encodes the SARS-CoV-2 spike protein. To make the vaccine, "[f]our spike protein sequences were retrieved from the first four available SARS-CoV-2 full genome sequences published on GISAID (Global Initiative on Sharing All Influenza Data). Three Spike sequences were 100% matched and one was considered an outlier (98.6% sequence identity with the other sequences). After performing a sequence alignment, the SARS-CoV-2 spike glycoprotein sequence was generated and an N-terminal IgE leader sequence was added. The highly optimized DNA sequence encoding SARS-CoV-2 IgE-spike was created using Inovio’s proprietary in silico Gene Optimization Algorithm to enhance expression and immunogenicity. The optimized DNA sequence was synthesized, digested with BamHI and XhoI, and cloned into the expression vector pGX0001 under the control of the human cytomegalovirus immediate-early promoter and a bovine growth hormone polyadenylation signal. The resulting plasmids were designated as pGX9501 and pGX9503, designed to encode the SARS-CoV-2 S protein from the three-matched sequences and the outlier sequence, respectively."&nbsp;<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239918/">SOURCE</a>: Smith et al. Nat Comm. 2020; 11: 2601
 
About INOVIO's DNA Medicines Platform
INOVIO has 15 DNA medicine clinical programs currently in development focused on infectious diseases, cancer and HPV-associated diseases. DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body.
INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO's proprietary hand-held smart device called CELLECTRA®. The CELLECTRA® uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen, which is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. INOVIO's DNA medicines do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured; the stability of the products, which do not require cold storage or transport; and the robust immune response, safety profile, and tolerability that have been observed in clinical trials.
With more than 3,000 patients receiving INOVIO investigational DNA medicines in more than 7,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.
<a href="https://ir.inovio.com/news-releases/news-releases-details/2021/INOVIOs-COVID-19-Vaccine-Candidate-INO-4800-Provides-Broad-Cross-reactive-Immune-Responses-In-Humans-Against-Variants-of-Concern/default.aspx">SOURCE</a>

INO-4800

Human immunodeficiency virus

Sexually transmitted infections

Inovio completed initial clinical studies of its HIV vaccine PENNVAX-B, targeting clade B viruses, to achieve proof of principle in generating potent immune responses using its SynCon® technology. In two published phase 1 studies, PENNVAX-B immunization via IM injection generated high levels of activated and antigen-specific CD8+ killer T cells. This ability uniquely positions PENNVAX as an important product candidate for both preventing and treating HIV infections. Using a $25 million contract from the NIH, Inovio designed its universal, multi-clade, multi-antigen PENNVAX-GP immunotherapy targeting the env, gag and pol antigens to provide coverage against all major HIV-1 clades. Inovio’s HIV development focus for both preventive and therapeutic purposes is on PENNVAX-GP.

PENNVAX-GP

Cervical cancer

MEDI0457

Arthritis

Prostate cancer

INO-5151 is a combined formulation of INO-5150 (with SynCon® antigens encoding for PSA and PSMA) and INO-9012 (DNA vector expressing interleukin 12).

INO-5151

Head and neck squamous cell carcinoma

Middle east respiratory syndrome

The consensus sequence for the MERS-CoV S protein vaccine was generated after analysis of the S protein genomic sequences, which were deposited in the GenBank-NCBI (National Center for Biotechnology Information) database. In previous reports, it was described that such consensus immunogens can induce broad cellular and humoral immune responses against diverse virus strains/isolates (<a href="https://stm.sciencemag.org/content/7/301/301ra132.full#ref-24">24</a>–<a href="https://stm.sciencemag.org/content/7/301/301ra132.full#ref-27">27</a>). Sequences from both clades A and B were included in the construct design. The MERS vaccine immunogen included several modifications to enhance in vivo expression, including the addition of a highly efficient immunoglobulin E (IgE) leader peptide sequence to facilitate expression and mRNA export. The insert was then subcloned into the pVax1 vector (<a href="https://stm.sciencemag.org/content/7/301/301ra132.full#F1">Fig. 1A</a>).
<a href="https://stm.sciencemag.org/content/7/301/301ra132.full">Source</a>

Inovio Pharmaceuticals

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