PR87482

PLYMOUTH MEETING, Pa., Jan. 6, 2021 /PRNewswire=KYODO JBN/ --

  -- DNA immunotherapy candidate VGX-3100 demonstrated clinically

     significant reduction of HPV-16/18-associated precancerous vulvar

     lesions in 63% of treated participants six months after treatment

  -- Phase 2 results indicate that VGX-3100 can be a safe, tolerable and

     efficacious adjunct to current standard of care for women with

     vulvar dysplasia

  -- Phase 3 trial planned in 2021

INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market

precisely designed DNA medicines to treat and protect people from infectious

diseases, cancer and HPV-associated diseases, today announced positive efficacy

results for an open-label Phase 2 trial of VGX-3100 to treat HPV-16 and

HPV-18-associated vulvar dysplasia. A 25% or more reduction in

HPV-16/18-associated vulvar HSIL (high-grade squamous intraepithelial lesion)

was observed for 63% of trial participants (12 of 19) treated with VGX-3100 at

six months post-treatment. Three out of the 20 participants with histology data

(15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the

healed area. By comparison, the spontaneous resolution of vulvar HSIL caused by

HPV-16/18 is estimated to be only 2%. The trial also showed VGX-3100 to be safe

and well-tolerated. Based upon these results INOVIO is planning to pursue Phase

3 development.

Dr. Robert Edwards, MD, Milton Lawrence McCall Professor and Chair, Department

of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh and

Principal Coordinating Investigator for the Phase 2 clinical trial said, "These

Phase 2 efficacy results are a very promising non-surgical advance for a

recalcitrant disease that normally requires repetitive ablation and excision

procedures to achieve disease and risk reduction, and may offer a more safe,

tolerable and efficacious treatment option for patients."

Prakash Bhuyan, M.D., Ph.D., Senior Vice President and Head of HPV Therapeutic

Clinical Development at INOVIO, said, "The reduction of precancerous disease

offers a meaningful improvement in the management of this devastating disease

and is a step forward towards the enhancement of women's healthcare."

VGX-3100 Phase 2 Vulvar Dysplasia Trial Highlights

     - Trial participants were 24 women between 22 and 70 years of age

       at entry and other than having HSIL were healthy.

     - 80% (20/25) had VIN3 disease (the more severe form of VIN) and

       88% (22/25) had a history of 1 or more recurrences

     - There were no discontinuations due to adverse events; five

       participants elected to withdraw for reasons unrelated to

       adverse events.

     - 19 participants had digital photography data, and 12 (63%)

       had clinically significant lesion reduction as defined by a

       reduction of lesion area of more than 25%.

     - 20 participants had histology and virology data and 3 (15%)

       resolved their vulvar HSIL and had no HPV-16/18 virus detectable

       in the healed area.

     - Histology was assessed by up to two independent pathologists and

       non-detectability of HPV-16/18 from lesion tissue using PCR

       (polymerase chain reaction)-based testing, at six months following

       the administration of VGX-3100.

     - Efficacy endpoints were measured six months post-treatment.

     - Safety will continue to be assessed for 18 months following the

       last dose.

     - The most observed adverse event was injection site pain, the

       majority of which were mild-to-moderate.

     - No cases of vulvar cancer have been observed in the trial.

For more information about the Phase 2 clinical trial, please visit

www.clinicaltrials.gov (search identifier NCT03180684).

About Vulvar Dysplasia

Vulvar dysplasia is a rare disease that affects women in immunocompetent and

immunocompromised populations. Fewer than 2% of women with HPV-16/18-associated

precancerous vulvar dysplasia exhibit spontaneous resolution.

HPV-16/18-associated precancerous vulvar lesions (vulvar HSIL) are known to be

difficult to treat, and typically require repeat ablation and excision

procedures to achieve disease and risk reduction. Without adequate treatment

vulvar HSIL can progress to vulvar cancer. In 2017, vulvar cancer was diagnosed

in 1354 women in the U.S. and 411 died from vaginal cancer.1

About VGX-3100

VGX-3100 is a DNA medicine in clinical trials for the treatment of three

HPV-16/18 related disease states – anal dysplasia, vulvar dysplasia and

cervical dysplasia. The cervical dysplasia program is in late Phase 3 clinical

trials (REVEAL1 and REVEAL2). VGX-3100 is designed to utilize the patient's own

immune system to clear HPV-16/18-associated high-grade precancerous lesions

with the aim of reducing the risk of cancer.

About INOVIO's HPV-Associated DNA Medicines Clinical Programs

This Phase 2 clinical trial builds on significant clinical benefits

demonstrated with INOVIO's HPV-associated DNA medicines across multiple

clinical trials. Specifically, VGX-3100 in a Phase 2 proof-of-concept trial for

cervical dysplasia demonstrated a response in 43 out of 107 patients in

regression of high-grade cervical lesions and elimination of the underlying HPV

infection2. A Phase 2 trial of VGX-3100 in the treatment of anal HSIL was also

conducted with positive efficacy results3. Additionally, two out of four

metastatic HPV-associated head and neck cancer patients treated with MEDI0457

and a PD-1 check point inhibitors in a Phase 1 trial experienced a long-term

complete response for more two years and counting; 18 out of 22 head and neck

patients treated with MEDI0457 have not progressed for over four years

post-treatment. Lastly, a pilot study of INOVIO's DNA medicine INO-3107 in

recurrent respiratory papillomatosis (RRP) resulted in two out of two patients

delaying surgery due to lack of tumor recurrence.

About INOVIO's DNA Medicines Platform

INOVIO has 15 DNA medicine clinical programs currently in development focused

on HPV-associated diseases, cancer, and infectious diseases, including

coronaviruses associated with MERS and COVID-19 diseases being developed under

grants from the Coalition for Epidemic Preparedness Innovations (CEPI) and the

U.S. Department of Defense. 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(R). The CELLECTRA device 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 other nucleic acid approaches,

such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce

the targeted antigen. The antigen is processed naturally in the cell and

triggers the desired T cell and antibody-mediated immune responses.

Administration with the CELLECTRA device ensures that the DNA medicine is

efficiently delivered directly into the body's cells, where it can go to work

to drive an immune response. 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 freezing in storage and

transport; and the robust immune response, safety profile, and tolerability

that have been observed in clinical trials.

With more than 2,000 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.

About INOVIO

INOVIO is a biotechnology company focused on rapidly bringing to market

precisely designed DNA medicines to treat and protect people from infectious

diseases, cancer, and diseases associated with HPV. 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

produce a robust and tolerable immune response. Specifically, INOVIO's lead

candidate VGX-3100, currently in Phase 3 trials for precancerous cervical

dysplasia, destroyed and cleared high-risk HPV 16 and 18 in a Phase 2b clinical

trial. High-risk HPV is responsible for 70% of cervical cancer, 91% of anal

cancer, and 69% of vulvar cancer. Also in development are programs targeting

HPV-related cancers and a rare HPV-related disease, recurrent respiratory

papillomatosis (RRP); non-HPV-related cancers glioblastoma multiforme (GBM) and

prostate cancer; as well as externally funded infectious disease DNA vaccine

development programs in Zika, Lassa fever, Ebola, HIV, and coronaviruses

associated with MERS and COVID-19 diseases. Partners and collaborators include

Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates

Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense

Advanced Research Projects Agency (DARPA)/Joint Program Executive Office for

Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)/Department

of Defense (DoD), HIV Vaccines Trial Network, International Vaccine Institute

(IVI), Kaneka Eurogentec, Medical CBRN Defense Consortium (MCDC), National

Cancer Institute, National Institutes of Health, National Institute of Allergy

and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer

Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics,

Thermo Fisher Scientific, University of Pennsylvania, Walter Reed Army

Institute of Research, and The Wistar Institute. INOVIO also is a proud

recipient of 2020 Women on Boards "W" designation recognizing companies with

more than 20% women on their board of directors. For more information, visit

www.inovio.com.

CONTACTS:

Investors: Ben Matone, 484-362-0076, ben.matone@inovio.com

Media: Jeff Richardson, 267-440-4211, jrichardson@inovio.com

This press release contains certain forward-looking statements relating to our

business, including our plans to develop and manufacture DNA medicines, our

expectations regarding our research and development programs, and our ability

to successfully manufacture and produce large quantities of our product

candidates if they receive regulatory approval. Actual events or results may

differ from the expectations set forth herein as a result of a number of

factors, including uncertainties inherent in preclinical studies, clinical

trials, product development programs and commercialization activities and

outcomes, our ability to secure sufficient manufacturing capacity to mass

produce our product candidates, the availability of funding to support

continuing research and studies in an effort to prove safety and efficacy of

electroporation technology as a delivery mechanism or develop viable DNA

medicines, our ability to support our pipeline of DNA medicine products, the

ability of our collaborators to attain development and commercial milestones

for products we license and product sales that will enable us to receive future

payments and royalties, the adequacy of our capital resources, the availability

or potential availability of alternative therapies or treatments for the

conditions targeted by us or our collaborators, including alternatives that may

be more efficacious or cost effective than any therapy or treatment that we and

our collaborators hope to develop, issues involving product liability, issues

involving patents and whether they or licenses to them will provide us with

meaningful protection from others using the covered technologies, whether such

proprietary rights are enforceable or defensible or infringe or allegedly

infringe on rights of others or can withstand claims of invalidity and whether

we can finance or devote other significant resources that may be necessary to

prosecute, protect or defend them, the level of corporate expenditures,

assessments of our technology by potential corporate or other partners or

collaborators, capital market conditions, the impact of government healthcare

proposals and other factors set forth in our Annual Report on Form 10-K for the

year ended December 31, 2019, our Quarterly Report on Form 10-Q for the quarter

ended September 30, 2020 and other filings we make from time to time with the

Securities and Exchange Commission. There can be no assurance that any product

candidate in our pipeline will be successfully developed, manufactured or

commercialized, that final results of clinical trials will be supportive of

regulatory approvals required to market products, or that any of the

forward-looking information provided herein will be proven accurate.

Forward-looking statements speak only as of the date of this release, and we

undertake no obligation to update or revise these statements, except as may be

required by law.

1 https://www.cdc.gov/cancer/vagvulv/statistics/#Ref2 accessed on 04JAN2021

2 Trimble et al., Lancet, 386, 10008, P2078-2088, 2015;

https://doi.org/10.1016/S0140-6736(15)00239-1

3 Presented at ASCCP 2020 Scientific Meeting

Source - INOVIO Pharmaceuticals, Inc.