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INOVIO Announces Positive Results from REVEAL 1, a Phase 3 Pivotal Trial Evaluating VGX-3100, its DNA-based HPV Immunotherapy for the Treatment of High-grade Precancerous Cervical Dysplasia Caused by HPV-16 and/or HPV-18

PLYMOUTH MEETING, Pa., March 2, 2021 /PRNewswire=KYODO JBN/ --

-- Trial achieved primary and secondary efficacy endpoints among all evaluable

subjects in the Phase 3 multi-center, randomized, double-blind,

placebo-controlled trial

-- VGX-3100 is the first DNA medicine to achieve efficacy endpoints in a Phase

3 clinical trial

-- INOVIO also continues to partner with QIAGEN to develop a pre-treatment

predictive biomarker with the goal of identifying women expected to respond to

VGX-3100

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 it met primary

and secondary endpoints among all evaluable subjects for the REVEAL 1 trial.

This trial is one of two ongoing pivotal, randomized, double-blind,

multi-center, placebo-controlled, Phase 3 trials (REVEAL 1 and REVEAL 2)

evaluating the safety, tolerability and efficacy of VGX-3100 to treat

HPV-16/18-associated cervical high-grade squamous intraepithelial lesions

(HSIL) using the company's proprietary CELLECTRA(R) 5PSP device.

The trial protocol-defined modified intention to treat (mITT) population

(N=193) includes all subjects with endpoint data. For the primary endpoint of

histopathological regression of HSIL combined with virologic clearance of

HPV-16 and/or HPV-18 at week 36, the percentage of responders was 23.7%

(31/131) in the treatment group, versus 11.3% (7/62) in the placebo group

(p=0.022; 12.4% difference in percentage, 95%CI: 0.4,22.5), thus achieving

statistical significance. All secondary efficacy endpoints were achieved. These

endpoints were: a) regression of cervical HSIL to normal tissue combined with

HPV-16/18 viral clearance, b) regression of cervical HSIL alone, c) regression

of cervical HSIL to normal tissue, and d) HPV-16/18 viral clearance alone.

The trial protocol-defined intention to treat (ITT) population (N=201) includes

all randomized subjects regardless of availability of endpoint data and defines

those without endpoint data as non-responders. There were eight such subjects

(seven in the treatment group, one in the placebo group). Including subjects

with missing endpoint data, the percentage of subjects meeting the primary

endpoint was 22.5% (31/138) in the treatment group, versus 11.1% (7/63) in the

placebo group (p=0.029; 11.4% difference in percentage, 95%CI: -0.4,21.2),

which was not statistically significant. All secondary endpoints were achieved

except for regression of cervical HSIL alone (12.8% difference in percentage,

95%CI: -0.6,24.5). The reasons for missing endpoint data were: one subject was

randomized but was never dosed, one withdrawal due to pregnancy, one withdrawal

due to administration error, one withdrawal due to post-administration pain,

one loss of follow-up due to COVID19-related travel restrictions, and three

losses to follow up due to undetermined reasons. A pre-specified per-protocol

(PP) analysis will also be performed upon trial completion.

There were no treatment-related serious adverse events and most adverse events

were self-resolving and were considered to be mild to moderate, consistent with

earlier clinical trials.

REVEAL 1 and REVEAL 2 are designed to assess and confirm the safety,

tolerability, and efficacy of VGX-3100. INOVIO will continue to follow subjects

in REVEAL 1 for safety and durability of response for 18 months following the

last administration and REVEAL 2 is currently enrolling subjects. INOVIO

expects to present REVEAL 1 findings at a scientific meeting this year.

Dr. J. Joseph Kim, President and CEO of INOVIO, said, "INOVIO is very proud to

advance VGX-3100 as the first DNA medicine to achieve efficacy endpoints in a

Phase 3 clinical trial in all evaluable subjects. We expect VGX-3100, if

approved, to be an important therapeutic option for those impacted by

HPV-16-/18-related disease. The REVEAL 1 efficacy and safety data also

represent an important proof-of-platform for INOVIO's DNA medicines.

Dr. Mark Einstein, MD, MS, FACS, FACOG, Principal Coordinating Investigator for

the REVEAL 1 trial, said, "There is a very significant need for a non-surgical

therapeutic for young women suffering from HPV-associated cervical dysplasia.  

These results are very encouraging and show that we are headed in the right

direction."

Dr. Prakash Bhuyan, MD, PhD, Senior Vice President and Head of HPV Therapeutic

Clinical Development at INOVIO, said, "We thank the investigators, site

personnel, and patients who made this research possible. We are excited to be

developing a new therapeutic designed to advance women's health. Through our

ongoing partnership with QIAGEN, we also plan to develop complementary a

biomarker diagnostic test that would enable practitioners to more effectively

identify women expected to respond to VGX-3100."

Biomarker Development

In the course of the REVEAL 1 and REVEAL 2 clinical trials, INOVIO continues to

pursue development of a pre-treatment RNA-based biomarker blood test which

could be used to identify prospective VGX-3100 patients who would be most

likely to respond to the immunotherapy. INOVIO believes this will be an

important element of VGX-3100 product and market development.

INOVIO announced in February that it is continuing its partnership with QIAGEN

to co-develop an in-vitro diagnostic based on RNA sequencing technology to

guide clinical decision-making for the use of VGX-3100 in cervical HSIL. This

technology had previously been employed in a post-hoc assessment of VGX-3100

Phase 2 data by INOVIO, in which 85% of VGX-3100 treated subjects who had the

biomarker experienced regression of HPV-16- and/or HPV-18-associated cervical

HSIL.

VGX-3100 REVEAL 1 Phase 3 Cervical Dysplasia Trial Design & Highlights

    -- Trial participants included 201 women, 18 years of age or older, who

       have histologically-confirmed cervical HSIL associated with HPV-16

       and/or HPV-18, but who were otherwise healthy.

       (ClinicalTrials.gov Identifier: NCT03185013)

    -- Participants received either VGX-3100 or placebo at 0, 4 and 12 weeks

       (randomized 2:1).

    -- Trial had 90% statistical power (two-sided 0.05 alpha-level) for the

       evaluation of the primary endpoint

    -- Results are based on the demonstration of having no evidence of HSIL

       associated with HPV-16 and/or HPV-18 from cervical biopsy samples and

       non-detectability of HPV-16 and/or HPV-18 using the cobas(R) HPV test

       from ThinPrep samples, at approximately 6 months following VGX-3100 or

       placebo administration.

    -- Based upon blinded aggregate data, the overall safety findings have

       been consistent with previously reported trials and considered

       generally safe and well tolerated.

    -- Data will continue to be collected until the end of the trial (week

       88).

About High Grade Cervical Dysplasia (Cervical HSIL)

Cervical HSIL is the pre-cancerous condition of the cervix that immediately

precedes the development of invasive cervical cancer. Cervical HSIL is caused

by persistent infection with high risk-HPV, including HPV-16 and HPV-18, which

collectively confer the highest risk for cervical HSIL development and cervical

cancer development. Estimates of the incidence rate of cervical HSIL over

recent years have indicated that up to 195,000 cases are diagnosed in the U.S.

annually.

About VGX-3100

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

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

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

trials (REVEAL 1 and REVEAL 2). VGX-3100 is designed to utilize the patient's

own immune system to clear HPV-16/18 virus and HPV-16-/18-associated high-grade

precancerous lesions with the aim of reducing the risk of cancer.

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 COVID-19 and MERS for which programs are being

developed with funding support from the U.S. Department of Defense and the

Coalition for Epidemic Preparedness Innovations (CEPI). 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 is designed to ensure 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 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.

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. INOVIO's lead immunotherapy

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

dysplasia, cleared high-risk HPV-16 and/or HPV-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 infectious disease DNA vaccine development programs

in coronaviruses associated with COVID-19 diseases and MERS, Lassa fever,

Ebola, and HIV. 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, +1 484-362-0076, ben.matone@inovio.com

Media: Jeff Richardson, +1 267-440-4211, jrichardson@inovio.com

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

business, including our plans to develop VGX-3100 for HPV-16/18-associated

cervical high-grade squamous intraepithelial lesions, plans to present clinical

data at an upcoming scientific meeting, the advantages and potential benefits

of our DNA medicines platform, as well as VGX-3100 and our other product

candidates, and our expectations regarding our research and development

programs, including our plans for a collaboration with QIAGEN to develop an

in-vitro diagnostic to guide clinical decision making for the use of VGX-3100.

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

product candidates, 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, 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.

SOURCE INOVIO Pharmaceuticals, Inc.