- New immunology data shows INO-3107 induced an expansion of
new clonal T cells in blood that were not detectable prior to
treatment
- New clonal T cells in the blood travelled to papilloma and
airway tissues and generated an inflammatory and anti-viral
response consistent with a reduced need for surgeries for patients
with recurrent respiratory papillomatosis (RRP) caused by HPV-6 and
HPV-11
- Data supporting mechanism of action for INO-3107 to
be presented at 36th International Papillomavirus Conference in
Edinburgh, UK
PLYMOUTH
MEETING, Pa., Nov. 13,
2024 /PRNewswire/ -- INOVIO (NASDAQ:INO), a
biotechnology company focused on developing and commercializing DNA
medicines to help treat and protect people from HPV-related
diseases, cancer, and infectious diseases, today announced new
immunology data that supports the clinical activity of its lead
product candidate, INO-3107, that was previously observed in a
Phase 1/2 trial of RRP patients. In that prior trial, patients
experienced a reduction in surgeries needed to control their RRP
caused by HPV-6 and HPV-11. In the recent immunology study,
INO-3107 induced the expansion of both existing and new clonal T
cells that travel from the blood to the papilloma and airway
tissues. The new clonal T cells accounted for the majority of
T cells observed in patient papilloma or airway tissue who showed
either a complete or partial response to treatment with INO-3107.
These new data build upon previously reported evidence that
INO-3107 elicits an antigen-specific immune response targeting
HPV-6 and HPV-11, to help eliminate or control RRP by reducing the
need for surgery.
"These new immunology data are consistent with the clinical
effect observed in our Phase 1/2 trial of elimination or reduction
in the incidence of papilloma in the airway of RRP patients," said
Dr. Matthew Morrow, INOVIO's Vice
President of Translational Sciences. "In a thorough immunological
assessment, we observed that T cell infiltration in airway
tissues of clinical responders was predominantly comprised of a T
cell population detectable only after administration of INO-3107.
This evidence supports the mechanism of action of INO-3107 and its
ability to induce antigen-specific cytotoxic T cells targeting
HPV-6 and HPV-11. Furthermore, this data adds to the body of
evidence indicating that DNA medicines are an effective CD8 T cell
generating platform."
Bettie M. Steinberg, Interim Dean
and Professor, Elmezzi Graduate School of Molecular Medicine,
Northwell Health, said, "This is very encouraging data. Not only
did most patients improve clinically with INO 3107 treatment, but
the induction of a systemic inflammatory T-cell response and new
T-cell clones that travel to the papilloma tissue to contribute to
a cytotoxic response shows that it is possible to effectively
address the immune dysregulation against HPV that is a hallmark of
RRP."
Summary of Immunology Data
The new immunology data is
to be presented at the 36th International Papillomavirus
Conference (November 12-15). It
builds on data presented at the American Association for Cancer
Research (AACR) Special Conference on October 19. Collectively, these immunology data
provide further support of INO-3107's ability to induce
antigen-specific T cell responses against HPV-6 and HPV-11 and
drive recruitment of T cells into papilloma and airway tissues of
RRP patients, which could potentially slow or eliminate papilloma
regrowth.
INOVIO conducted a number of immunological assessments on blood
samples taken throughout the trial and tissue samples taken at the
beginning and end of its 52-week Phase 1/2 trial involving 32 adult
RRP patients. The immunological testing showed INO-3107
produced:
- Induction of T cell responses specific for HPV-6 and HPV-11,
including cytotoxic CD8+ T cells still present at week 52,
indicating an establishment of memory response
- Expansion of new clonal T cell populations in peripheral blood
that travel to papilloma or airway tissues
- Induction of inflammatory responses in papilloma and airway
tissue, including:
- Interferon, cytokine and chemokine signaling
- Adaptive and innate immune cell infiltration, with emphasis on
T cells
- Cytotoxic signatures of infiltrated T cells in papilloma/airway
tissue, and direct evidence of increased overall T cell
infiltration compared to pre-treatment
- Clinical activity not impacted by immunosuppressive papilloma
microenvironment
About RRP
RRP is a debilitating and rare disease caused primarily by HPV-6
and/or HPV-11. RRP is characterized by the development of small,
wart-like growths, or papillomas, in the respiratory tract. While
papillomas are generally benign, they can cause severe,
life-threatening airway obstruction and respiratory complications.
RRP can also significantly affect quality of life for patients by
affecting the voice box, limiting the ability to speak effectively.
Surgery to remove papillomas is the standard of care for RRP;
however, the papillomas often grow back. INOVIO's market research
to date with patients and healthcare professionals indicates that a
reduction of even one surgery matters, because every surgery poses
a significant risk of causing permanent damage to the vocal cords.
The most widely cited U.S. epidemiology data published in 1995
estimated that there were 14,000 active cases and about 1.8 per
100,000 new cases in adults each year.
About INO-3107
INO-3107 is an investigational DNA
medicine designed to elicit an antigen-specific T cell response
against both HPV-6 and HPV-11 proteins. These targeted T cells are
designed to seek out and kill HPV-6 and HPV-11 infected cells, with
the aim of potentially preventing or slowing the growth of new
papillomas. In a Phase 1/2 clinical trial conducted with INO-3107,
81.3% (26/32) of patients had a decrease in surgical interventions
in the year after INO-3107 administration compared to the prior
year, including 28.1% (9/32) that required no surgical intervention
during or after the dosing window. Patients in the trial had a
median range of 4 surgeries (2-8) in the year prior to dosing.
After dosing, there was a median decrease of 3 surgical
interventions (95% confidence interval -3, -2). At the outset of
the trial (Day 0), patients had a clinically warranted procedure to
have RRP tissue surgically removed, but any surgery performed after
Day 0 during the dosing window was counted against the efficacy
endpoint. Treatment with INO-3107 generated a strong immune
response in the trial, inducing activated CD4 T cells and activated
CD8 T cells with lytic potential. T-cell responses were also
observed at Week 52, indicating a persistent cellular memory
response. INO-3107 was well tolerated, with trial participants
experiencing mostly low-grade (Grade 1) treatment-emergent adverse
effects such as injection site pain and fatigue. Like other DNA
medicines, INO-3107 has shown the ability to generate
antigen-specific T cells that is not affected by anti-vector
immunity impacting immunogenicity, either before administration or
after the first dose unlike other T-cell generating platforms such
as viral vectors. This feature of DNA medicines is anticipated to
allow INO-3107 to maintain T cell response and overall efficacy,
which could make it an important therapeutic option for a majority
of RRP patients.
The FDA previously granted INO-3107 Orphan Drug designation and
Breakthrough Therapy designation and has advised INOVIO that it can
submit a biologics license application under the FDA's accelerated
approval program using data from INOVIO's already completed Phase
1/2 trial. The European Commission granted INO-3107 Orphan Drug
designation. In addition, INOVIO has CE-marked its
CELLECTRA® delivery device in the EU, which allows INOVIO to
commercialize the device in the EU and other geographies that
recognize CE-marking. The United
Kingdom awarded INO-3107 the Innovation Passport. This
designation serves as the entry point to the Innovative Licensing
and Access Pathway (ILAP), which aims to accelerate time to market
and facilitate patient access to medicines.
About INOVIO's DNA Medicines Platform
INOVIO's DNA
medicines platform has two innovative components: precisely
designed DNA plasmids, delivered by INOVIO's proprietary
investigational medical device, CELLECTRA®. INOVIO uses proprietary
technology to design its DNA plasmids, which are small circular DNA
molecules that work like software the body's cells can download to
produce specific proteins to target and fight disease. INOVIO's
proprietary CELLECTRA® delivery devices are designed to optimally
deliver its DNA medicines to the body's cells without requiring
chemical adjuvants or lipid nanoparticles and without the risk of
the anti-vector response historically seen with viral vector
platforms.
About INOVIO
INOVIO is a biotechnology company focused
on developing and commercializing DNA medicines to help treat and
protect people from HPV-related diseases, cancer, and infectious
diseases. INOVIO's technology optimizes the design and delivery of
innovative DNA medicines that teach the body to manufacture its own
disease-fighting tools. For more information, visit
www.inovio.com.
Forward-Looking Statements
This press release contains
certain forward-looking statements relating to our business,
including our plans to develop and commercialize DNA medicines and
expectations regarding our research and development programs,
including timelines and prospects for regulatory approval,
expectations regarding INO-3107's ability to maintain T cell
response and overall efficacy, as well as benefits for patients.
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 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, 2023, our Quarterly
Report on Form 10-Q for the quarter ended June 30, 2024, 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 the
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.
Contacts
Media: Jennie
Willson (267) 429-8567 jennie.willson@inovio.com
Investors: Thomas Hong (267)
440-4298 thomas.hong@inovio.com
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SOURCE INOVIO Pharmaceuticals, Inc.