Country for PR: United States
Contributor: PR Newswire New York
Thursday, December 10 2020 - 00:00
INOVIO's VGX-3100 Demonstrates Positive Phase 2 Efficacy In Treatment of Precancerous Anal Dysplasia Caused by HPV-16/18
PLYMOUTH MEETING, Pa., Dec. 9, 2020 /PRNewswire/ --

-- DNA immunotherapy candidate VGX-3100 demonstrated resolution of 
HPV-16/18-associated precancerous anal lesions in 50% of treated patients six 
months after treatment 

-- Current standard of care for anal dysplasia typically requires surgical 
excision, electro-cautery or laser therapy, and without adequate treatment can 
progress to anal cancer 

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 diseases associated with HPV, today announced positive 
Phase 2 efficacy results demonstrating that DNA medicine VGX-3100, the 
company's lead immunotherapy asset, showed resolution of HPV-16/18-associated 
precancerous anal lesions (HSIL) in 50% (11 of 22) of subjects six months 
following the start of treatment. The open label, single arm trial also showed 
VGX-3100 to be safe and well-tolerated in treating men and women with 
HPV-16-/18-associated anal dysplasia. INOVIO plans to pursue a registrational 
Phase 3 clinical trial for HPV-16-/18-associated anal dysplasia as well as to 
apply for rare and orphan disease designation for this indication in 2021.

Dr. Céline Bouchard, Gynecologist and Anoscopist at Centre Médical Santé Femme 
in Québec City, Canada and Coordinating Principal Investigator for the Phase 2 
trial, said, "Results of this trial are very promising and may offer a safe and 
efficacious new therapeutic option for patients suffering from this 
debilitating condition."

VGX-3100 Phase 2 Anal Dysplasia Trial Highlights

  -- Enrolled 23 men and women 18 years of age or older. One subject
     discontinuation occurred due to an event related to a pre-existing
     condition of depression. 
  -- Trial participants were men and women between 29 and 76 years of age at
     entry and other than having high grade anal squamous intraepithelial
     lesions were otherwise healthy. 
  -- The relative proportion of anal dysplasia severity at baseline was skewed
     toward the more severe condition of AIN-3 disease (78% [18/23] of
     subjects). Subjects had a median of 4 lesions (range 2-7). 
  -- Results are based on the demonstration of having no evidence of dysplasia
     from anal biopsy samples as assessed by two independent pathologists and
     non-detectability of HPV-16 or HPV-18 from lesion tissue using PCR-based
     testing, at six months following VGX-3100 administration. 
  -- 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 discontinuations occurred due to treatment-related adverse events 
  -- No treatment-emergent serious adverse events have been observed. 
  -- No cases of anal cancer have been observed in the trial. 

For more information about the Phase 2 trial, please visit (search identifier NCT03499795).

Prakash Bhuyan, M.D., Ph.D., Senior Vice President and Head of HPV Therapeutic 
Clinical Development at INOVIO, said, "Anal dysplasia is a rare disease that is 
typically treated via surgical excision, electro-cautery or laser therapy, with 
up to 50% of patients experiencing disease recurrence within one year of 
surgical treatment. We are encouraged by these positive results from our Phase 
2 trial and look forward to continuing our work in Phase 3 trials to develop a 
systemic DNA-based immunotherapy that leverages our DNA medicines platform in 
order to improve the current standard of care."

INOVIO also has an ongoing partnership with the AIDS Malignancy Consortium 
(AMC) to evaluate VGX-3100 in HIV-positive adult men and women. This ongoing 
open-label, multi-center Phase 2 study is designed to evaluate the safety and 
efficacy of VGX-3100 administered by intramuscular (IM) injection with 
CELLECTRA® delivery system in adult men and women who are HIV-positive with 
anal HSIL associated with HPV-16 and/or HPV-18. For additional information 
about the AMC-partnered study, please visit (search 
identifier NCT03603808).

About Anal Dysplasia

Anal dysplasia is a rare disease that affects men and women in both 
immunocompetent and immunocompromised populations. Fewer than 1 in 5 people 
with HPV-16- or HPV-18-associated precancerous dysplasia exhibit spontaneous 
resolution at one year. Without adequate treatment, anal dysplasia can progress 
to anal cancer. 

HPV-16/18 cause more than 90% of all anal cancer, which is now considered one 
the most rapidly rising causes of cancer incidence and mortality. According to 
the American Cancer Society, anal cancer will claim the lives of more than 
1,300 people in the U.S. and 8,590 news cases (5,900 in women and 2,690 in men) 
will be diagnosed in 2020. According to a study published November 2019 in the 
Journal of the National Cancer Institute, from 2001 to 2015 the overall 
incidence of anal cancer increased by 2.7% per year and mortality jumped by 
3.1% each year.

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 in multiple clinical 
trials. Specifically, VGX-3100 in a Phase 2 proof-of-concept trial for cervical 
dysplasia demonstrated a complete response in 43 out of 107 patients in 
regression of high-grade cervical lesions and elimination of the underlying HPV 
infection. Additionally, two out of four metastatic HPV-associated head and 
neck cancer patients treated with MEDI0457 and a PD-1 check point inhibitor in 
a Phase 1 trial experienced a long-term complete response for more two years 
and counting. Lastly, a pilot study of INOVIO's DNA medicine INO-3107 in 
HPV-caused 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®. 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), 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

Media: Jeff Richardson, +1 267-440-4211,
Investors: Ben Matone, +1 484-362-0076,

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.


SOURCE:  INOVIO Pharmaceuticals, Inc.