PR84032

INOVIO's INO-5401 in Combination with PD-1 Inhibitor Libtayo(R) (cemiplimab) Demonstrates 85% of Newly Diagnosed Glioblastoma Patients Are Alive 12 Months Following Treatment

PLYMOUTH MEETING, Pennsylvania, May 14, 2020 /PRNewswire=KYODO JBN/ --

- Results Will Be Presented at the American Society of Clinical Oncology (ASCO)

2020 Annual Meeting

INOVIO (NASDAQ: INO) today announced that 85 percent (44 out of 52) of patients

newly diagnosed with the deadly brain cancer glioblastoma multiforme (GBM) who

received the company's DNA medicine INO-5401, in combination with INO-9012 and

PD-1 inhibitor Libtayo(R) (cemiplimab), were alive for at least 12 months or

more (overall survival at 12 months: OS12) following treatment. These data will

be featured at an oral poster presentation at the ASCO 2020 Virtual Scientific

Program, May 29-31, 2020.

GBM is the most common and aggressive type of brain cancer. Currently, the

median overall survival with standard of care therapy, which includes radiation

and chemotherapy (temozolomide: TMZ), is approximately 15 to 22 months.

The Phase 1/2 clinical trial demonstrated that 84.4% percent (27 of 32) of

patients with MGMT promoter unmethylated tumors, and 85% (17 of 20) of patients

with MGMT promoter methylated tumors were alive at 12 months. This promising

clinical result is coupled with a robust immunological response to all three

cancer antigens in INO-5401, including human telomerase (hTERT), Wilms Tumor-1

(WT-1) and prostate specific membrane antigen (PSMA). Activated, cytotoxic T

cells directed towards these cancer antigens commonly expressed on GBM tumors

were detected in all patients tested to date and continue to support the

immunogenic potential of INOVIO's DNA medicines. Importantly, INO-5401 +

INO-9012 was safe and well-tolerated when given not only with radiation and

TMZ, but also with PD-1 inhibition with Libtayo, which is being jointly

developed by Regeneron and Sanofi. These results are being presented in a

virtual format at the 2020 Annual ASCO meeting (Abstract #2514).

Dr. David Reardon, Clinical Director, Center for Neuro-Oncology of Dana-Farber

Cancer Institute and coordinating principal investigator of GBM-001 said,

"Although these data are preliminary, and follow-up remains early, this novel

combination of a cancer antigen-specific, T cell generating DNA medicine with a

PD-1 inhibitor is exciting and may overcome more than 20 years of a standard of

care that has proven sub-optimal for our patients with GBM. A tolerable, new

combination of medicines utilizing a novel mechanism of action, such as that

provided by INO-5401 and INO-9012 with cemiplimab, is very welcome for this

hard-to-treat brain cancer, especially when shown to be tolerable with

standards such as radiation and chemotherapy, and when demonstrating the

immunogenicity seen in the GBM-001 study."

Dr. J. Joseph Kim, INOVIO's President & CEO, said, "While we recognize these

data are early, we are very excited to see robust immunogenicity and the

potential for extending survival, coupled with a clear ability to be able to

combine not only with the standard of care, but with a checkpoint inhibitor,

Libtayo. Where others have failed with single-agent checkpoint inhibition in

GBM, our DNA medicine combined with Libtayo and standard of care has

demonstrated clear immunogenicity and the potential to extend overall survival."

In a previous announcement, INOVIO reported key interim data from the

52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter

methylated patients and 75% (24 of 32) unmethylated patients were

progression-free at six months (PFS6) measured from the time of their first

dose, exceeding historical standard-of-care data.

This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited

supportive safety, tolerability, and immunogenicity data and suggested an

acceptable safety profile consistent with that of Libtayo and INOVIO's platform

technology. The majority of patients tested had a T cell immune response to one

or more tumor-associated antigens encoded by INO-5401. Immune responses to all

three tumor-associated antigens were demonstrated in this study. INOVIO plans

to report 18-month overall survival data later this year.

Study Design

The trial was designed to evaluate safety, immunogenicity and preliminary

efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation

and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is

a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients

with GBM. There are two cohorts in this trial. Cohort A includes 32

participants with a tumor with an unmethylated

O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter.

Cohort B includes 20 participants with a tumor with a MGMT methylated promoter.

Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and

on the same dosing schedule, and both cohorts received radiation and

temozolomide (TMZ). Interim data presented here and at SITC was obtained as of

October 2019 and overall survival data at 18 months is expected in Q4 2020. For

more information of the clinical study, see www.clinicaltrials.gov, identifier

NCT03491683.

Poster Details

Abstract/Poster 2514

Poster Discussion Session: Central Nervous System Tumors

The ASCO 2020 Virtual Scientific Program runs from May 29 -31.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive type of brain cancer and remains a

devastating disease for both patients and caregivers. Its prognosis is

extremely poor, despite a limited number of new therapies approved over the

last 10 years. The median overall survival for patients receiving standard of

care therapy is approximately 15 to 22 months and the median progression-free

survival is approximately 7 months. In the U.S., the estimated annual incidence

of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at

diagnosis is 65 years.

About INO-5401 and INO-9012

INO-5401 encodes for INOVIO's SynCon(R) 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.

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). 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 demonstrated in clinical trials.

With more than 2,000 patients receiving INOVIO investigational DNA medicines in

more than 6,000 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 protect and treat 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)/Department of Defense (DOD), GeneOne

Life Science/VGXI, HIV Vaccines Trial Network, International Vaccine Institute

(IVI), 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, Roche/Genentech,

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:

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

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

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

business, including our plans to develop DNA medicines, our expectations

regarding our research and development programs, including the planned

initiation and conduct of preclinical studies and clinical trials, and the

availability and timing of data from those studies and trials. Actual events or

results may differ from the expectations set forth herein as a result of a

number of factors, including uncertainties inherent in pre-clinical studies,

clinical trials, product development programs and commercialization activities

and outcomes, 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 March 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.