INOVIO Presents Clinical Results of its DNA Medicines INO-5401 + INO-9012 in Novel Combination with PD-1 Inhibitor Libtayo(R) (cemiplimab)

INOVIO Pharmaceuticals, Inc.

2020/11/22 16:05

AsiaNet  86780


INOVIO Presents Clinical Results of its DNA Medicines INO-5401 + INO-9012 in Novel Combination with PD-1 Inhibitor Libtayo(R) (cemiplimab) in the Treatment of Newly Diagnosed Glioblastoma Multiforme at Society for Neuro-Oncology 2020 Annual Meeting


PLYMOUTH MEETING, Pennsylvania Nov. 20, 2020 /PRNewswire=KYODO JBN/ --


-- Interim review in newly diagnosed glioblastoma patients provides OS18 data,

demonstrates immunogenicity and tolerability in a majority of patients


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

market precisely designed DNA medicines to treat and protect people from

infectious diseases and cancer, announced today that data from the company's

novel combination trial of DNA medicines INO-5401 and INO-9012 in combination

with PD-1 inhibitor Libtayo(R)(cemiplimab) in the treatment of newly diagnosed

glioblastoma (GBM), will be presented by Dr. David Reardon in the plenary

session at the Society for Neuro-Oncology (SNO) 2020 Annual Meeting. The study

demonstrated that INO-5401 + INO-9012 with Libtayo, radiation (RT) and

temozolomide (TMZ) are tolerable, immunogenic, and may improve median survival

for patients with newly diagnosed GBM. Survival data at 18 months showed that

70% (14/20) of MGMT promoter methylated GBM patients were alive, and 50%

(16/32) of MGMT promoter unmethylated patients, which are the more difficult to

treat group, were alive after 18 months. Median overall survival in the

unmethylated GBM patients was 17.9 months, which compares favorably to

historical controls; Median OS for methylated patients has not yet been reached

and the study is ongoing.


Dr. David Reardon, Clinical Director of the Center for Neuro-Oncology at the

Dana-Farber Cancer Institute and coordinating principal investigator of GBM-001

said, "This is a landmark combination trial in which a novel DNA vaccine is

combined with a checkpoint inhibitor and radiation and chemotherapy. We look

forward to continuing to review these data, with an eye towards those patients

who are most likely to benefit from this innovative approach and to see

whether, over time, there is an extension of survival in these very

hard-to-treat patients. Coupling immune response with clinical outcome may

prove insightful."


Interim data demonstrated that in the MGMT promoter unmethylated cohort, 19/22

(86%) subjects to date had an IFN-gamma T cell response that increased over

baseline to one or more of the antigens encoded by INO-5401. In the MGMT

promoter methylated cohort, 16/17 (94%) subjects to date had an IFN-gamma

response that increased over baseline to one or more of the antigens encoded by

INO-5401. The novel combination of INO-5401 + INO-9012 continues to demonstrate

a well-tolerated safety profile when given not only with radiation and TMZ, but

also with PD-1 blockade by Libtayo, which is being jointly developed by

Regeneron and Sanofi.


Dr. Jeffrey Skolnik, INOVIO's senior vice president, clinical development,

said, "INO-5401 + INO-9012, with Libtayo and RT/TMZ, generates cancer

antigen-specific T cells that may be able to attack GBM and provide a survival

advantage. We are using our knowledge of immunology to define a patient

population for which this novel DNA medicine plus checkpoint inhibitor

combination may offer a survival advantage, by continuing to assess all of our

data: efficacy, safety and most important, immunogenicity and tissue expression



Additional data will be provided in the coming months, including correlative

immunology and tissue data, as well as total study drug exposure and

concomitant medication use.


INO-5401, INO-9012 and Libtayo, and the combination of these products have not

been approved or evaluated by any Regulatory Authority worldwide for the

treatment of newly diagnosed GBM.


Presentation Details


Abstract: LTBK-01


Title: "INO-5401 and INO-9012 delivered intramuscularly (IM) with

electroporation (EP) in combination with cemiplimab (REGN2810) in newly

diagnosed glioblastoma"


Presenting Author: Dr. David Reardon


Plenary Session Date and Time: 2020 SNO Annual Meeting, Plenary 1A, Friday,

November 20, 2020 beginning at 11 a.m. EST


Study Design


The trial was designed to evaluate safety, immunogenicity and 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 TMZ. For

more information of the clinical study, see, identifier



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) 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.




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), 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




Investors: Ben Matone, +1-484-362-0076,

Media: Jeff Richardson, +1-267-440-4211,


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, 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 pre-clinical 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.


SOURCE:  INOVIO Pharmaceuticals, Inc.