UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
For
the fiscal year ended December 31, 2022.
or
For
the transition period from _______ to _______
COMMISSION
FILE NO.: 001-15911
IMUNON,
INC.
(Exact
Name of Registrant as Specified in Its Charter)
(Address of Principal Executive Offices) (Zip Code)
Registrant’s
telephone number, including area code: (609)896-9100
Securities
registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock, Par Value $0.01 Per Share IMNN The Nasdaq Stock Market LLC
Securities
registered pursuant to section 12(g) of the Act: None
Indicate
by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate
by check mark if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate
by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports) and (2)
has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate
by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule
405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant
was required to submit such files). Yes ☒ No ☐
Indicate
by check mark whether the Registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company or an emerging growth company. See the definitions of “large accelerated filer”, “accelerated filer”,
“smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large Accelerated Filer ☐ Accelerated Filer ☐
Non-accelerated Filer ☐ Smaller Reporting Company ☒
Emerging Growth Company ☐
If
an emerging growth company, indicate by check mark if the Registrant has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate
by check mark whether the Registrant has filed a report on and attestation to its management’s assessment of the effectiveness
of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered
public accounting firm that prepared or issued its audit report. ☐
Indicate
by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Securities Exchange Act of 1934). Yes ☐
No ☒
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant
included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation
received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
The
aggregate market value of the common stock held by non-affiliates of the Registrant was approximately $13.1 million as of June 30, 2022
(the last business day of the Registrant’s most recently completed second fiscal quarter) based on the closing sale price of $1.84
for the Registrant’s common stock on that date as reported by The Nasdaq Capital Market (“NASDAQ”). For purposes of
this calculation, shares of common stock held by directors, officers and stockholders who own greater than 10% of the Registrant’s
outstanding stock at June 30, 2022, were excluded. This determination of executive officers and directors as affiliates is not necessarily
a conclusive determination for any other purpose.
As
of March 28, 2023, 9,089,789 shares of the Registrant’s common stock were issued and outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE
Portions
of the Registrant’s definitive Proxy Statement to be filed for its 2023 Annual Meeting of Stockholders are incorporated by reference
into Part III hereof. Such Proxy Statement will be filed with the Securities and Exchange Commission within 120 days of the end of the
fiscal year covered by this Annual Report on Form 10-K.
IMUNON,
INC.
FORM
10-K
TABLE
OF CONTENTS
PART I
ITEM 1. BUSINESS 1
FORWARD-LOOKING STATEMENTS 1
OVERVIEW 2
IMMUNO-ONCOLOGY PROGRAM 2
THERAPLAS Technology Platform 2
Ovarian Cancer Overview 3
IMNN-001 Immunotherapy 3
OVATION I Study 3
OVATION 2 Study 5
PLACCINE DNA VACCINE TECHNOLOGY PLATFORM 7
COVID-19 Vaccine Overview 8
Our Next Generation Vaccine Initiative 8
THERMODOX® DIRECTED CHEMOTHERAPY 10
OPTIMA Study 11
Investigator-Sponsored Studies with ThermoDox® 11
BUSINESS STRATEGY AND DEVELOPMENT PLAN 12
RESEARCH AND DEVELOPMENT EXPENDITURES 12
GOVERNMENT REGULATION 13
MANUFACTURING AND SUPPLY 24
SALES AND MARKETING 24
PRODUCT LIABILITY AND INSURANCE 25
COMPETITION 25
ThermoDox ® 26
INTELLECTUAL PROPERTY 26
Patents and Proprietary Rights 26
EMPLOYEES 27
COMPANY INFORMATION 27
AVAILABLE INFORMATION 28
ITEM 1A. RISK FACTORS 28
ITEM 1B. UNRESOLVED STAFF COMMENTS 43
ITEM 2. PROPERTIES 43
ITEM 3. LEGAL PROCEEDINGS 44
ITEM 4. MINE SAFETY DISCLOSURES 45
i
IMUNON,
INC.
FORM
10-K
TABLE
OF CONTENTS (continued)
PART II
Market for Our Common Stock 45
Record Holders 45
Dividend Policy 45
Unregistered Sales of Equity Securities 45
Issuer Purchases of Equity Securities 45
ITEM 6. SELECTED FINANCIAL DATA 45
Overview 46
Business Plan 55
Financing Overview 57
Critical Accounting Policies and Estimates 60
Results of Operations 60
Financial Condition, Liquidity and Capital Resources 62
Off-Balance Sheet Arrangements 63
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 63
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 64
ITEM 9A. CONTROLS AND PROCEDURES 64
ITEM 9B. OTHER INFORMATION 65
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 65
PART III
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 65
ITEM 11. EXECUTIVE COMPENSATION 65
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 66
PART IV
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 66
1. FINANCIAL STATEMENTS 66
2. FINANCIAL STATEMENT SCHEDULES 66
ii
ITEM 1. BUSINESS
FORWARD-LOOKING
STATEMENTS
Certain
of the statements contained in this Annual Report on Form 10-K (this “Annual Report”) are forward-looking and constitute
forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”),
and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). Forward-looking statements may relate
to such matters as anticipated financial performance, business prospects, technological developments, product pipelines, clinical trials
and research and development activities, the adequacy of capital reserves and anticipated operating results and cash expenditures, current
and potential collaborations, strategic alternatives and other aspects of our present and future business operations and similar matters.
These statements involve known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual
results, levels of activity, performance, or achievements to be materially different from any future results, levels of activity, performance,
or achievements expressed or implied by such forward-looking statements. Such factors include, among other things, unforeseen changes
in the course of research and development activities and in clinical trials; possible changes in cost, timing and progress of development,
preclinical studies, clinical trials and regulatory submissions; our collaborators’ ability to obtain and maintain regulatory approval
of any of our drug candidates; possible changes in capital structure, financial condition, future working capital needs and other financial
items; changes in approaches to medical treatment; introduction of new products by others; success or failure of our current or future
collaboration arrangements, risks and uncertainties associated with possible acquisitions of other technologies, assets or businesses;
our ability to obtain additional funds for our operations; our ability to obtain and maintain intellectual property protection for our
technologies and drug candidates and our ability to operate our business without infringing the intellectual property rights of others;
our reliance on third parties to conduct preclinical studies or clinical trials; the rate and degree of market acceptance of any approved
drug candidates; possible actions by customers, suppliers, strategic partners, potential strategic partners, competitors and regulatory
authorities; compliance with listing standards of The Nasdaq Capital Market; and those listed under “Risk Factors” below
and elsewhere in this Annual Report.
In
some cases, you can identify forward-looking statements by terminology such as “expect,” “anticipate,” “estimate,”
“plan,” “believe,” “could,” “intend,” “predict,” “may,” “should,”
“will,” “would” and words of similar import regarding the Company’s expectations. Forward-looking statements
are only predictions. Actual events or results may differ materially. Although we believe that our expectations are based on reasonable
assumptions within the bounds of our knowledge of our industry, business and operations, we cannot guarantee that actual results will
not differ materially from our expectations. In evaluating such forward-looking statements, you should specifically consider various
factors, including the risks outlined under “Risk Factors.” The discussion of risks and uncertainties set forth in this Annual
Report is not necessarily a complete or exhaustive list of all risks facing the Company at any particular point in time. We operate in
a highly competitive, highly regulated and rapidly changing environment and our business is in a state of evolution. Therefore, it is
likely that new risks will emerge, and that the nature and elements of existing risks will change, over time. It is not possible for
management to predict all such risk factors or changes therein, or to assess either the impact of all such risk factors on our business
or the extent to which any individual risk factor, combination of factors, or new or altered factors, may cause results to differ materially
from those contained in any forward-looking statement. Except as required by law, we assume no obligation to revise or update any forward-looking
statement that may be made from time to time by us or on our behalf for any reason, even if new information becomes available in the
future. Unless the context requires otherwise or unless otherwise noted, all references in this Annual Report to “Imunon”,
“the Company”, “we”, “us”, or “our” are to Imunon, Inc., a Delaware corporation and its
wholly owned subsidiaries, CLSN Laboratories, Inc., also a Delaware corporation and Celsion GmbH, a Swiss corporation.
Trademarks
The
Imunon brand and product names, including but not limited to Imunon® and ThermoDox®, contained in this
document are trademarks, registered trademarks or service marks of Imunon, Inc. or its subsidiary in the United States (the “U.S.”)
and certain other countries. This document also contains references to trademarks and service marks of other companies that are the property
of their respective owners.
OVERVIEW
On
September 19, 2022, Celsion Corporation announced a corporate name change to Imunon, Inc., reflecting the evolution of the Company’s
business focus and its commitment to developing cutting-edge immunotherapies and next-generation vaccines to treat cancer and infectious
diseases. The Company’s common stock continues to trade on the Nasdaq Stock Market under the new ticker symbol “IMNN”
effective as of the opening of trading on September 21, 2022. The Company filed an amendment to its Articles of Incorporation to effect
the new corporate name.
Imunon,
Inc. (“Imunon” and the “Company”) is a fully integrated, clinical stage biotechnology company focused on advancing
a portfolio of innovative treatments that harness the body’s natural mechanisms to generate safe, effective, and durable responses
across a broad array of human diseases, constituting a differentiating approach from conventional therapies. Imunon has two platform
technologies: Our TheraPlas® platform for the development of immunotherapies and other anti-cancer nucleic acid-based therapies,
and our PLACCINE platform for the development of nucleic acid vaccines for infectious diseases and cancer. The Company’s lead clinical
program, IMNN-001 (formerly known as GEN-1), is a DNA-based immunotherapy for the localized treatment of advanced ovarian cancer currently
in Phase II development. IMNN-001 works by instructing the body to produce safe and durable levels of powerful cancer fighting molecules,
such as interleukin-12 and interferon gamma, at the tumor site. Additionally, the Company is conducting preclinical proof-of-concept
studies on a nucleic acid vaccine candidate targeting SARS-CoV-2 virus in order to validate its PLACCINE platform. Imunon’s platform
technologies are based on the delivery of nucleic acids with novel synthetic delivery systems that are independent of viral vectors or
devices. We will continue to leverage these platforms and to advance the technological frontier of plasmid DNA to better serve patients
with difficult to treat conditions.
IMMUNO-ONCOLOGY
Program
On
June 20, 2014, the Company completed the acquisition of substantially all of the assets of EGEN, Inc., a privately held corporation located
in Huntsville, Alabama. Pursuant to the Asset Purchase Agreement, CLSN Laboratories acquired all of EGEN’s right, title and interest
in substantially all of the assets of EGEN, including cash and cash equivalents, patents, trademarks and other intellectual property
rights, clinical data, certain contracts, licenses and permits, equipment, furniture, office equipment, furnishings, supplies and other
tangible personal property. A key asset acquired from EGEN was the TheraPlas technology platform. The first drug candidate developed
from this technology platform is IMNN-001.
THERAPLAS
Technology Platform
TheraPlas
is a technology platform for the delivery of DNA and mRNA therapeutics via synthetic non-viral carriers and is capable of providing cell
transfection for double-stranded DNA plasmids and large therapeutic RNA segments such as mRNA. There are two components of the TheraPlas
system, a plasmid DNA or mRNA payload encoding a therapeutic protein, and a delivery system. The delivery system is designed to protect
the DNA/mRNA from degradation and promote trafficking into cells and through intracellular compartments. We designed the delivery system
of TheraPlas by chemically modifying the low molecular weight polymer to improve its gene transfer activity without increasing toxicity.
We believe that TheraPlas may be a viable alternative to current approaches to gene delivery due to several distinguishing characteristics,
including enhanced molecular versatility that allows for complex modifications to potentially improve activity and safety.
The
design of the TheraPlas delivery system is based on molecular functionalization of polyethyleneimine (“PEI”), a cationic
delivery polymer with a distinct ability to escape from the endosomes due to heavy protonation. The transfection activity and toxicity
of PEI is tightly coupled to its molecular weight; therefore, the clinical application of PEI is limited. We have used molecular functionalization
strategies to improve the activity of low molecular weight PEIs without augmenting their cytotoxicity. In one instance, chemical conjugation
of a low molecular weight branched BPEI1800 with cholesterol and polyethylene glycol (“PEG”) to form PEG-PEI-Cholesterol
(“PPC”) dramatically improved the transfection activity of BPEI1800 following in vivo delivery. Together, the cholesterol
and PEG modifications produced approximately 20-fold enhancement in transfection activity. Biodistribution studies following intraperitoneal
or subcutaneous administration of DNA/PPC nanocomplexes showed DNA delivery localized primarily at the injection site with only a small
amount escaping into the systemic circulation. PPC is the delivery component of our lead TheraPlas product, IMNN-001, which is in clinical
development for the treatment of ovarian cancer. The PPC manufacturing process has been scaled up from bench scale (1-2 g) to 0.6Kg,
and several lots produced using current Good Manufacturing Practice (“cGMP”) have been produced with reproducible quality.
We
believe that TheraPlas has emerged as a viable alternative to current approaches due to several distinguishing characteristics such as
strong molecular versatility that may allow for complex modifications to potentially improve activity and safety with little difficulty.
The biocompatibility of these polymers reduces the risk of adverse immune response, thus allowing for repeated administration. Compared
to naked DNA or cationic lipids, TheraPlas is generally safer, more efficient, and cost effective. We believe that these advantages place
Imunon in a position to capitalize on this technology platform.
Ovarian
Cancer Overview
Ovarian
cancer is the most lethal of gynecological malignancies among women with an overall five-year survival rate of 45%. This poor outcome
is due in part to the lack of effective prevention and early detection strategies. There were approximately 20,000 new cases of ovarian
cancer in the U.S. in 2021 with an estimated 13,000 deaths. Mortality rates for ovarian cancer declined very little in the last forty
years due to the unavailability of detection tests and improved treatments. Most women with ovarian cancer are not diagnosed until Stages
III or IV, when the disease has spread outside the pelvis to the abdomen and areas beyond causing swelling and pain. The five-year survival
rates for Stages III and IV are 39 percent and 17 percent, respectively. First-line chemotherapy regimens are typically platinum-based
combination therapies. Although this first line of treatment has an approximate 80 percent response rate, 55 to 75 percent of women will
develop recurrent ovarian cancer within two years and ultimately will not respond to platinum therapy. Patients whose cancer recurs or
progresses after initially responding to surgery and first-line chemotherapy have been divided into one of the two groups based on the
time from completion of platinum therapy to disease recurrence or progression. This time period is referred to as platinum-free interval.
The platinum-sensitive group has a platinum-free interval of longer than six months. This group generally responds to additional treatment
with platinum-based therapies. The platinum-resistant group has a platinum-free interval of shorter than six months and is resistant
to additional platinum-based treatments. Pegylated liposomal doxorubicin, topotecan, and Avastin are the only approved second-line therapies
for platinum-resistant ovarian cancer. The overall response rate for these therapies is 10 to 20 percent with median overall survival
(“OS”) of eleven to twelve months. Immunotherapy is an attractive novel approach for the treatment of ovarian cancer particularly
since ovarian cancers are considered immunogenic tumors. IL-12 is one of the most active cytokines for the induction of potent anti-cancer
immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. The precedence for a therapeutic role of
IL-12 in ovarian cancer is based on epidemiologic and preclinical data.
IMNN-001
(formerly GEN-1) Immunotherapy
IMNN-001
is a DNA-based immunotherapeutic drug candidate for the localized treatment of ovarian cancer by intraperitoneally administering an Interleukin-12
(“IL-12”) plasmid formulated with our proprietary TheraPlas delivery system. In this DNA-based approach, the immunotherapy
is combined with a standard chemotherapy drug, which can potentially achieve better clinical outcomes than with chemotherapy alone. We
believe that increases in IL-12 concentrations at tumor sites for several days after a single administration could create a potent immune
environment against tumor activity and that a direct killing of the tumor with concomitant use of cytotoxic chemotherapy could result
in a more robust and durable antitumor response than chemotherapy alone. We believe the rationale for local therapy with IMNN-001 is
based on the following:
● Local therapy is ideal for long-term maintenance therapy.
OVATION
I Study. In February 2015, we announced that the U.S. Food and Drug Administration (“FDA”) accepted, without objection,
the Phase I dose-escalation clinical trial of IMNN-001 in combination with the standard of care in neoadjuvant ovarian cancer (the “OVATION
I Study”). On September 30, 2015, we announced enrollment of the first patient in the OVATION I Study. The OVATION I Study was
designed to:
(iii) attempt to define an optimal dose for a follow-on Phase I/II study.
In
addition, the OVATION I Study established a unique opportunity to assess how cytokine-based compounds such as IMNN-001, directly affect
ovarian cancer cells and the tumor microenvironment in newly diagnosed ovarian cancer patients. The study was designed to characterize
the nature of the immune response triggered by IMNN-001 at various levels of the patients’ immune system, including:
We
initiated the OVATION I Study at four clinical sites at the University of Alabama at Birmingham, Oklahoma University Medical Center,
Washington University in St. Louis, and the Medical College of Wisconsin. During 2016 and 2017, we announced data from the first fourteen
patients in the OVATION I Study. On October 3, 2017, we announced final translational research and clinical data from the OVATION I Study.
Key
translational research findings from all evaluable patients are consistent with the earlier reports from partial analysis of the data
and are summarized below:
The
Company also reported encouraging clinical data from the first fourteen patients who completed treatment in the OVATION I Study. IMNN-001
plus standard chemotherapy produced no dose limiting toxicities and positive dose dependent efficacy signals which correlate well with
positive surgical outcomes as summarized below:
On
March 26, 2020, the Company announced with Medidata, a Dassault Systèmes company, that examining matched patient data provided
by Medidata in a synthetic control arm (“SCA”) with results from the Company’s completed Phase Ib dose-escalating OVATION
I Study showed positive results in progression-free survival (“PFS”). The hazard ratio (“HR”) was 0.53 in the
ITT group, showing strong signals of efficacy. The Company believes these data may warrant consideration of strategies to accelerate
the clinical development program for IMNN-001 in newly diagnosed, advanced ovarian cancer patients by the FDA. In its March 2019 discussion
with the Company, the FDA noted that preliminary findings from the Phase Ib OVATION I Study were exciting but lacked a control group
to evaluate IMNN-001’s independent impact on impressive tumor response, surgical results and PFS. The FDA encouraged the Company
to continue its IMNN-001 development program and consult with FDA with new findings that may have a bearing on designations such as Fast
Track and Breakthrough Therapy.
SCAs
have the potential to revolutionize clinical trials in certain oncology indications and some other diseases where a randomized control
is not ethical or practical. SCAs are formed by carefully selecting control patients from historical clinical trials to match the demographic
and disease characteristics of the patients treated with the new investigational product. SCAs have been shown to mimic the results of
traditional randomized controls so that the treatment effects of an investigational product can be visible by comparison to the SCA.
SCAs can help advance the scientific validity of single arm trials, and in certain indications, reduce time and cost, and expose fewer
patients to placebos or existing standard-of-care treatments that might not be effective for them.
On
July 29, 2021, the Company announced final progression free survival (“PFS”) results from the OVATION I Study published in
the Journal of Clinical Cancer Research. Median PFS in patients treated per protocol (n=14) was 21 months and was 18.4 months for the
intent-to-treat (“ITT”) population (n=18) for all dose cohorts, including three patients who dropped out of the study after
13 days or less, and two patients who did not receive full NAC and IMNN-001 cycles. Under the current standard of care, in women with
Stage III/IV ovarian cancer undergoing NAC, their disease progresses within about 12 months on average. The results from the OVATION
I Study support continued evaluation of IMNN-001 based on promising tumor response, as reported in the PFS data, and the ability for
surgeons to completely remove visible tumors at interval debulking surgery. IMNN-001 was well tolerated, and no dose-limiting toxicities
were detected. Intraperitoneal administration of IMNN-001 was feasible with broad patient acceptance.
OVATION
2 Study. The Company held an Advisory Board Meeting on September 27, 2017 with the clinical investigators and scientific experts
including those from Roswell Park Cancer Institute, Vanderbilt University Medical School, and M.D. Anderson Cancer Center to review and
finalize clinical, translational research and safety data from the OVATION I Study to determine the next steps forward for our IMNN-001
immunotherapy program. On November 13, 2017, the Company filed its Phase I/II clinical trial protocol with the FDA for IMNN-001 for the
localized treatment of ovarian cancer. The protocol is designed with a single dose escalation phase to 100 mg/m2 to identify a safe
and tolerable dose of IMNN-001 while maximizing an immune response. The Phase I portion of the study will be followed by a continuation
at the selected dose in approximately 110 patients randomized Phase II study.
In
the OVATION 2 Study, patients in the IMNN-001 treatment arm will receive IMNN-001 plus chemotherapy pre- and post-interval debulking
surgery (“IDS”). The OVATION 2 Study will include up to 110 patients with Stage III/IV ovarian cancer, with 12 to 15 patients
in the Phase I portion and up to 95 patients in Phase II. The study is powered to show a 33% improvement in the primary endpoint, PFS,
when comparing IMNN-001 with neoadjuvant + adjuvant chemotherapy versus neoadjuvant + adjuvant chemotherapy alone. The PFS primary analysis
will be conducted after at least 80 events have been observed or after all patients have been followed for at least 16 months, whichever
is later.
In
March 2020, the Company announced encouraging initial clinical data from the first 15 patients enrolled in the Phase I portion of the
OVATION 2 Study for patients newly diagnosed with Stage III and IV ovarian cancer. The OVATION 2 Study combines IMNN-001, the Company’s
IL-12 gene-mediated immunotherapy, with standard-of-care neoadjuvant chemotherapy (“NACT”). Following NACT, patients undergo
interval debulking surgery (IDS), followed by three additional cycles of chemotherapy.
IMNN-001
plus standard NACT produced positive dose-dependent efficacy results, with no dose-limiting toxicities, which correlates well with successful
surgical outcomes as summarized below:
% of Patients R0 Resections
On
March 23, 2020, the Company announced that the European Medicines Agency (the “EMA”) Committee for Orphan Medicinal Products
(“COMP”) has recommended that IMNN-001 be designated as an orphan medicinal product for the treatment of ovarian cancer.
IMNN-001 is an IL-12 DNA plasmid vector encased in a non-viral nanoparticle delivery system, which enables cell transfection followed
by persistent, local secretion of the IL-12 protein. IMNN-001 previously received orphan designation from the FDA.
In
February 2021, the Company announced that it has received Fast Track designation from the FDA for IMNN-001, its DNA-mediated IL-12 immunotherapy
currently in Phase II development for the treatment of advanced ovarian cancer and also provided an update on the OVATION 2 Study. The
Company reported that approximately one-third, or 34 patients, of the anticipated 110 patients had been enrolled into the OVATION 2 Study,
of which 20 are in the treatment arm and 14 are in the control. Of the 34 patients enrolled in the trial, 27 patients have had their
interval debulking surgery with the following results:
● 58% of patients in the control arm had an R0 resection.
In
June 2022, the Company announced that following a pre-planned interim safety review of 87 as treated patients (46 patients in the experimental
arm and 41 patients in the control arm) randomized in the OVATION 2 Study, the Data Safety Monitoring Board (“DSMB”) unanimously
recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2. The DSMB also determined that
safety is satisfactory with an acceptable risk/benefit, and that patients tolerate IMNN-001 during a course of treatment that lasts up
to six months. No dose-limiting toxicities were reported. Interim clinical data from patients who have undergone interval debulking surgery
showed that the IMNN-001 treatment arm is continuing to show improvement in R0 surgical resection rates and CRS 3 chemotherapy response
scores over the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic
tumor remains in the tumor bed. The chemotherapy response score is a three-tier standardized scoring system for histological tumor regression
into complete/near complete (CRS 3), partial (CRS 2) and no/minimal (CRS 1) response based on omental examination.
In
September 2022, the Company announced that its Phase I/II OVATION 2 Study with IMNN-001 in advanced ovarian cancer has completed enrollment
with 110 patients. Topline results are expected in the first half of 2024.
IMNN-001
in Combination with Avastin. In February 2023, the Company and Break Through Cancer, a public foundation dedicated to supporting
translational research in the most difficult-to-treat cancers that partners with top cancer research centers, announce the commencement
of patient enrollment in a collaboration to evaluate IMNN-001 in combination with Avastin® (bevacizumab) in patients with advanced
ovarian cancer in the frontline, neoadjuvant clinical setting.
This
Phase 1/2 study, titled “Targeting Ovarian Cancer Minimal Residual Disease (MRD) Using Immune and DNA Repair Directed Therapies,”
is expected to enroll 50 patients with Stage III/IV advanced ovarian cancer and is being led by principal investigator Amir Jazaeri,
M.D., Vice Chair for Clinical Research and Director of the Gynecologic Cancer Immunotherapy Program in the Department of Gynecologic
Oncology and Reproductive Medicine at MD Anderson. Dana-Farber Cancer Institute, The Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins and Memorial Sloan Kettering Cancer Center will also be participating in the trial. In addition, The Koch Institute for Integrative
Cancer Research at the Massachusetts Institute of Technology (MIT) will provide artificial intelligence services including biomarker
and genomic analysis.
Patients
will be randomized 1:1 in a two-arm trial. The primary endpoint is second look laparoscopy (SLL) and the secondary endpoint is progression-free
survival (PFS). Initial SLL data are expected within one year from the completion of enrollment and final PFS data are expected approximately
three years from the completion of enrollment.
PLACCINE
DNA VACCINE TECHNOLOGY PLATFORM
In
January 2021, the Company announced the filing of a provisional U.S. patent application for a novel DNA-based, investigational vaccine
for preventing or treating infections from a broad range of infectious agents including the coronavirus disease using its PLACCINE DNA
vaccine technology platform (“PLACCINE”). The provisional patent covers a family of novel composition of multi-cistronic
vectors and polymeric nanoparticles that comprise the PLACCINE DNA vaccine platform technology for preventing or treating infectious
agents that have the potential for global pandemics, including the SARS-CoV-2 virus and its variations, using the Company’s TheraPlas
platform technology.
Imunon’s
PLACCINE DNA vaccine technology platform is characterized by a single multi-cistronic DNA plasmid vector expressing multiple pathogen
antigens delivered with a synthetic delivery system. We believe it is adaptable to creating vaccines for a multitude of pathogens, including
emerging pathogens leading to pandemics as well as infectious diseases that have yet to be effectively addressed with current vaccine
technologies. This flexible vaccine platform is well supported by an established supply chain to produce any plasmid vector and its assembly
into a respective vaccine formulation.
The
need for new vaccine technologies is urgent. Since 1980 more than 80 pathogenic viruses have been discovered, yet fewer than 4% have
a commercially available prophylactic vaccine. We have engaged with the Biomedical Advanced Research and Development Authority (BARDA),
a division of the U.S. Department of Health and Human Services, to pursue certain pathogens BARDA has identified as the most urgent and
the most important.
PLACCINE
is an extension of the Company’s synthetic, non-viral TheraPlas delivery technology currently in a Phase II trial for the treatment
of late-stage ovarian cancer with IMNN-001. Imunon’s proprietary multifunctional DNA vaccine technology concept is built on the
flexible PLACCINE technology platform that is amenable to rapidly responding to the SARS-CoV-2 virus, as well as possible future mutations
of SARS-CoV-2, other future pandemics, emerging bioterrorism threats, and novel infectious diseases. Imunon’s extensive experience
with TheraPlas suggests that the PLACCINE-based nanoparticles are stable at storage temperatures of 4oC to 25oC,
making vaccines developed on this platform easily suitable for broad world-wide distribution.
Imunon’s
vaccine approach is designed to optimize the quality of the immune response dictating the efficiency of pathogen clearance and patient
recovery. Imunon has taken a multivalent approach in an effort to generate an even more robust immune response that not only results
in a strong neutralizing antibody response, but also a more robust and durable T-cell response. Delivered with Imunon’s synthetic
polymeric system, the proprietary DNA plasmid is protected from degradation and its cellular uptake is facilitated.
COVID-19
Vaccine Overview
Emerging
data from the recent literature indicates that the quality of the immune response as opposed to its absolute magnitude is what dictates
SARS-CoV-2 viral clearance and recovery and that an ineffective or non-neutralizing enhanced antibody response might actually exacerbate
disease. The first-generation COVID-19 vaccines were developed for rapid production and deployment and were not optimized for generating
cellular responses that result in effective viral clearance. Though early data has indicated some of these vaccines to be over 95% effective,
these first-generation vaccines were primarily designed to generate a strong antibody response, and while they have been shown to provide
prophylactic protection against disease, the durability of this protection is currently unclear. Most of these vaccines have been specifically
developed to target the SARS-CoV-2 Spike (S) protein (antigen), though it is known that restricting a vaccine to a sole viral antigen
creates selection pressure that can serve to facilitate the emergence of viral resistance. Indeed, even prior to full vaccine rollout,
it has been observed that the S protein is a locus for rapid evolutionary and functional change as evidenced by the D614G, Y453F, 501Y.V2,
and VUI-202012/01 mutations/deletions. This propensity for mutation of the S protein leads to future risk of efficacy reduction over
time as these mutations accumulate.
Our
Next Generation Vaccine Initiative
Imunon’s
vaccine candidate comprises a single plasmid vector containing the DNA sequence encoding multiple SARS-CoV-2 antigens. Delivery will
be evaluated intramuscularly, intradermally, or subcutaneously with a non-viral synthetic DNA delivery carrier that facilitates vector
delivery into the cells of the injected tissue and has potential immune adjuvant properties. Unique designs and formulations of Imunon
vaccine candidates may offer several potential key advantages. The synthetic polymeric DNA carrier is an important component of the vaccine
composition as it has the potential to facilitate the vaccine immunogenicity by improving vector delivery and, due to potential adjuvant
properties, attract professional immune cells to the site of vaccine delivery.
Future
vaccine technology will need to address viral mutations and the challenges of efficient manufacturing, distribution, and storage. We
believe an adaptation of our TheraPlas technology, PLACCINE, has the potential to meet these challenges. Our approach is described in
our provisional patent filing and is summarized as a DNA vaccine technology platform characterized by a single plasmid DNA with multiple
coding regions. The plasmid vector is designed to express multiple pathogen antigens. It is delivered via a synthetic delivery system
and has the potential to be easily modified to create vaccines against a multitude of infectious diseases, addressing:
We
are conducting preliminary research associated with our recently announced proprietary DNA vaccine platform provisional patent filing.
At the same time, we are redoubling our efforts and R&D resources in our immuno-oncology and next generation vaccine program.
On
September 2, 2021, the Company announced results from preclinical in vivo studies showing production of antibodies and cytotoxic
T-cell response specific to the spike antigen of SARS-CoV-2 when immunizing BALB/c mice with the Company’s next-generation PLACCINE
DNA vaccine platform. Moreover, the antibodies to SARS-CoV-2 spike antigen prevented the infection of cultured cells in a viral neutralization
assay. The production of antibodies predicts the ability of PLACCINE to protect against SARS-CoV-2 exposure, and the elicitation of cytotoxic
T-cell response shows the vaccine’s potential to eradicate cells infected with SARS-CoV-2. These findings demonstrate the potential
immunogenicity of Imunon’s PLACCINE DNA vaccine, which is intended to provide broad-spectrum protection and resistance against
variants by incorporating multiple viral antigens, to improve vaccine stability at storage temperatures of 4o C and above,
and to facilitate cheaper and easier manufacturing.
On
January 31, 2022, the Company announced it had engaged BIOQUAL, Inc., a preclinical testing contract research organization, to conduct
a non-human primate (NHP) challenge study with Imunon’s DNA-based approach for a SARS-CoV-2 vaccine. The NHP pilot study follows
the generation of encouraging mouse data and will evaluate the Company’s lead vaccine formulations for safety, immunogenicity and
protection against SARS-CoV-2. In completed preclinical studies, Imunon demonstrated safe and efficient immune responses including IgG
response, neutralizing antibodies and T-cell responses that parallel the activity of commercial vaccines following intramuscular (IM)
administration of novel vaccine compositions expressing a single viral antigen. In addition, vector development has shown promise of
neutralizing activity against a range of SARS-CoV-2 variants. Imunon’s novel DNA-based vaccines have been based on a simple intramuscular
injection that does not require viral encapsulation or special equipment for administration.
In
April 2022, the Company presented its PLACCINE platform technology at the 2022 World Vaccine Congress. In an oral presentation during
a Session on Cancer and Immunotherapy, Dr. Khursheed Anwer, the Company’s Chief Science Officer, highlighted the Company’s
technology platform in his presentation entitled: “Novel DNA Approaches for Cancer Immunotherapies and Multivalent Infectious
Disease Vaccines.” PLACCINE is demonstrating the potential to be a powerful platform that provides for rapid design capability
for targeting two or more different variants of a single virus in one vaccine. There is a clear public health need for vaccines today
that address more than one strain of viruses, like COVID-19, which have fast evolving variant capability to offer the widest possible
protection. Murine model data has thus far been encouraging and suggests that the Company’s approach provides not only flexibility,
but also the potential for efficacy comparable to benchmark COVID-19 commercial vaccines with durability to protect for more than 6 months.
In
September 2022, the Company provided an update on the progress made in the development of a DNA-based vaccine using its PLACCINE platform
technology. The Company reported evidence of IgG, neutralizing antibody, and T-cell responses to its SARS-CoV-2 PLACCINE vaccines in
normal mice. In this murine model, the Company’s multivalent PLACCINE vaccine targeted against two different variants showed to
be immunogenic as determined by the levels of IgG, neutralizing antibodies, and T-cell responses. Additionally, our multivalent vaccine
was equally effective against two different variants of the COVID-19 virus while the commercial mRNA vaccine appeared to have lost some
activity against the newer variant. The murine model data has thus far been encouraging and suggests that the Company’s approach
provides not only flexibility, but also the potential for efficacy comparable to benchmark COVID-19 commercial vaccines with durability
to protect expected to be greater than 6 months.
Final
data from its now completed proof-of-concept mouse challenge study confirmed that a PLACCINE DNA-based vaccine can produce robust levels
of IgG, neutralizing antibodies, and T-cell responses. The data demonstrates the ability of the Company’s PLACCINE vaccine to protect
a SARS-CoV-2 mouse model in a live viral challenge. In the study, mice were vaccinated with a PLACCINE vaccine expressing the SARS-CoV-2
spike antigen from the D614G variant or the Delta variant, or a combination vaccine expressing both the D614G and Delta spike variants.
The vaccination was administered by intramuscular injection on Day 0 and Day 14, followed by challenge with live SARS-CoV-2 virus on
Day 42. All three vaccines, including the single and dual antigen vaccines, were found to be safe and elicited IgG responses and inhibited
the viral load by 90-95%. The dual antigen vaccine was equally effective against both variants of the SARS CoV-2 virus.
In
October 2022, the Company reported partial results from an ongoing non-human primate study designed to examine the immunogenicity of
its proprietary PLACCINE vaccine which supports PLACCINE as a viable alternative to mRNA vaccines. The study examined a single plasmid
DNA vector containing the SARS-CoV-2 Alpha variant spike antigen formulated with a synthetic DNA delivery system and administered by
intramuscular injection. In the study, Cynomolgus monkeys were vaccinated with the PLACCINE vaccine or a commercial mRNA vaccine on Day
1, 28 and 84. Analysis of blood samples for IgG and neutralizing antibodies showed evidence of immunogenicity both in PLACCINE and mRNA
vaccinated subjects. Analysis of bronchoalveolar lavage for viral load by quantitative PCR showed viral clearance by >90% of the non-vaccinated
controls. Viral clearance from nasal swab followed a similar pattern in a majority of vaccinated animals and a similar clearance profile
was observed when viral load was analyzed by the tissue culture infectious dose method.
In
March 2023, the Company announced final results from the non-human primate study involving three vaccine-treated non-human primates.
The final data are consistent with the earlier data and show excellent immunological response and viral clearance in non-human primates.
More specifically, in this NHP study, we examined PLACCINE activity against more advanced SARS-CoV-2 variants and at a DNA dose that
was not previously tested in NHP and demonstrated robust IgG responses, neutralizing antibody responses and complete clearance of virus
following the challenge as seen in the previous study.
In
a recent mouse study, a single dose of PLACCINE vaccine without a booster dose produced longer duration of IgG responses and higher T-cell
activation than an mRNA vaccine. A 12-month PLACCINE stability study has now completed 9 months demonstrating continued drug stability
at 4oC (standard refrigerated temperature).
During
2023, the Company intends to choose the next pathogen target for our PLACCINE modality and plans to hold a pre-Investigational New Drug
(pre-IND) meeting with the U.S. Food and Drug Administration in advance of beginning human testing of a SARS-CoV-2 seasonal booster vaccine.
Of note, the design of that trial will also inform the path for the next pathogen we will study, perhaps in early 2024. Incremental investments
to generate novel vaccine designs with optimized antigens will allow Imunon to quickly generate early clinical data against additional
pathogen targets that position the company to partner with large vaccine companies who will fund remaining clinical development.
THERMODOX®
- DIRECTED CHEMOTHERAPY
Liposomes
are manufactured submicroscopic vesicles consisting of a discrete aqueous central compartment surrounded by a membrane bilayer composed
of naturally occurring lipids. Conventional liposomes have been designed and manufactured to carry drugs and increase residence time,
thus allowing the drugs to remain in the bloodstream for extended periods of time before they are removed from the body. However, the
current existing liposomal formulations of cancer drugs and liposomal cancer drugs under development do not provide for the immediate
release of the drug and the direct targeting of organ specific tumors, two important characteristics that are required for improving
the efficacy of cancer drugs such as doxorubicin. A team of research scientists at Duke University developed a heat-sensitive liposome
that rapidly changes its structure when heated to a threshold minimum temperature of 39.5o to 42o Celsius. Heating creates
channels in the liposome bilayer that allow an encapsulated drug to rapidly disperse into the surrounding tissue. This novel, heat-activated
liposomal technology is differentiated from other liposomes through its unique low heat-activated release of encapsulated chemotherapeutic
agents. We are able to use several available focused-heat technologies, such as radiofrequency ablation (“RFA”), microwave
energy and high intensity focused ultrasound (“HIFU”), to activate the release of drugs from our novel heat sensitive liposomes.
OPTIMA
Study
The
OPTIMA Study represents an evaluation of ThermoDox® in combination with a first line therapy, RFA, for newly diagnosed,
intermediate stage HCC patients. The OPTIMA Study was designed to enroll up to 550 patients globally at approximately 65 clinical sites
in the U.S., Canada, European Union (“EU”), China and other countries in the Asia-Pacific region and will evaluate ThermoDox®
in combination with standardized RFA, which will require a minimum of 45 minutes across all investigators and clinical sites for
treating lesions three to seven centimeters, versus standardized RFA alone. The primary endpoint for the OPTIMA Study is OS, and the
secondary endpoints are progression free survival and safety. The statistical plan calls for two interim efficacy analyses by an independent
Data Monitoring Committee (“DMC”).
In
August 2018, the Company announced that the OPTIMA Study was fully enrolled. On August 5, 2019, the Company announced that the prescribed
number of OS events had been reached for the first prespecified interim analysis of the OPTIMA Phase III Study. Following preparation
of the data, the first interim analysis was conducted by the DMC. The DMC’s pre-planned interim efficacy review followed 128 patient
events, or deaths, which occurred in August 2019. On November 4, 2019, the Company announced that the DMC unanimously recommended the
OPTIMA Study continue according to protocol. The recommendation was based on a review of blinded safety and data integrity from 556 patients
enrolled in the OPTIMA Study. Data presented demonstrated that PFS and OS data appeared to be tracking with patient data observed at
a similar point in the Company’s subgroup of patients followed prospectively in the earlier Phase III HEAT Study, upon which the
OPTIMA Study was based. On April 15, 2020, the Company announced that the prescribed minimum number of events of 158 patient deaths had
been reached for the second pre-specified interim analysis of the OPTIMA Phase III Study. The hazard ratio for success at 158 deaths
is 0.70, which represents a 30% reduction in the risk of death compared with RFA alone. On July 13, 2020, the Company announced that
it has received a recommendation from the DMC to consider stopping the global OPTIMA Study. The recommendation was made following the
second pre-planned interim safety and efficacy analysis by the DMC on July 9, 2020. The DMC analysis found that the pre-specified boundary
for stopping the trial for futility of 0.900 was crossed with an actual value of 0.903. However, the 2-sided p-value of 0.524 for this
analysis provided uncertainty, subsequently, the DMC left the final decision of whether or not to stop the OPTIMA Study to the Company.
There were no safety concerns noted during the interim analysis. The Company followed the advice of the DMC and considered its options
either to stop the study or continue to follow patients after a thorough review of the data, and an evaluation of our probability of
success.
On
August 4, 2020, the Company issued a press release announcing it would continue following patients for OS, noting that the unexpected
and marginally crossed futility boundary, suggested by the Kaplan-Meier analysis at the second interim analysis on July 9, 2020, may
be associated with a data maturity issue. On October 12, 2020, the Company provided an update on the ongoing data analysis from its Phase
III OPTIMA Study with ThermoDox® as well as growing interest among clinical investigators in conducting studies with ThermoDox®
as a monotherapy or in combination with other therapies. On February 11, 2021, the Company provided a final update on the Phase
III OPTIMA Study and the decision to stop following patients in the Study. Independent analyses conducted by a global biometrics contract
research organization and the NIH, did not find any evidence of significance or factors that would justify continuing to follow patients
for OS. Therefore, the Company notified all clinical sites to discontinue following patients. The OPTIMA Study database of 556 patients
has been frozen at 185 patient deaths. While the analyses did identify certain patient subgroups that appear to have had a clinical benefit,
the Company concluded that it would not be in its best interest to pursue these retrospective findings as the regulatory hurdles supporting
further discussion will be significant.
Investigator-Sponsored
Studies with ThermoDox®
The
Company continues working closely and supporting investigations by others to evaluate the use of ThermoDox for the treatment of various
cancers. Following inquiries from the NIH, we renewed our Cooperative Research and Development Agreement (“CRADA”) with the
Institute at a nominal cost, one goal of which is to pursue their interest in a study of ThermoDox® to treat patients
with bladder cancer. Importantly, the Company is developing a business model to support these investigator-sponsored studies in a manner
that will not interfere with its current focus on our IMNN-001 program and vaccine development initiative.