UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
For
the fiscal year ended December 31, 2023.
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. ☐
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). ☐
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 ☒
The
aggregate market value of the common stock held by non-affiliates of the Registrant was approximately $11.9 million as of June 30, 2023
(the last business day of the Registrant’s most recently completed second fiscal quarter) based on the closing sale price of $1.29
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, 2023, were excluded. This determination of executive officers and directors as affiliates is not necessarily
a conclusive determination for any other purpose.
As
of March 26, 2024, 9,399,789 shares of the Registrant’s common stock were issued and outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE
None.
IMUNON,
INC.
FORM
10-K
TABLE
OF CONTENTS
PART I
ITEM 1. BUSINESS 1
FORWARD-LOOKING STATEMENTS 1
OVERVIEW 2
THERAPLAS MODALITY: IMNN-001 DEVELOPMENT PROGRAM 3
Ovarian Cancer Overview 3
IMNN-001 Immunotherapy 3
OVATION I Study 3
OVATION 2 Study 5
PLACCINE DNA VACCINE TECHNOLOGY PLATFORM 8
COVID-19 Vaccine Overview 8
Our Next Generation Vaccine Initiative 9
THERMODOX® DIRECTED CHEMOTHERAPY 11
OPTIMA Study 11
BUSINESS STRATEGY AND DEVELOPMENT PLAN 12
RESEARCH AND DEVELOPMENT EXPENDITURES 14
GOVERNMENT REGULATION 14
MANUFACTURING AND SUPPLY 25
SALES AND MARKETING 26
PRODUCT LIABILITY AND INSURANCE 26
COMPETITION 26
INTELLECTUAL PROPERTY 27
Patents and Proprietary Rights 27
EMPLOYEES 28
COMPANY INFORMATION 28
AVAILABLE INFORMATION 28
ITEM 1A. RISK FACTORS 29
ITEM 1B. UNRESOLVED STAFF COMMENTS 45
ITEM 1C. CYBERSECURITY 45
ITEM 2. PROPERTIES 45
ITEM 3. LEGAL PROCEEDINGS 46
ITEM 4. MINE SAFETY DISCLOSURES 46
i
IMUNON,
INC.
FORM
10-K
TABLE
OF CONTENTS (continued)
PART II
Market for Our Common Stock 47
Record Holders 47
Dividend Policy 47
Unregistered Sales of Equity Securities 47
Issuer Purchases of Equity Securities 47
ITEM 6. SELECTED FINANCIAL DATA 47
Overview 48
Business Plan 48
Financing Overview 50
Critical Accounting Policies and Estimates 51
Results of Operations 52
Financial Condition, Liquidity and Capital Resources 55
Off-Balance Sheet Arrangements 56
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 56
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 56
ITEM 9A. CONTROLS AND PROCEDURES 56
ITEM 9B. OTHER INFORMATION 57
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 57
PART III
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 57
ITEM 11. EXECUTIVE COMPENSATION 62
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 70
PART IV
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 71
1. FINANCIAL STATEMENTS 71
2. FINANCIAL STATEMENT SCHEDULES 71
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; uncertainties and assumptions regarding the potential worsening global economic conditions and the recent disruptions to, and
volatility in, financial markets in the U.S. and worldwide resulting from the COVID-19 pandemic, the Russian invasion of Ukraine and
the unrest in the Middle East on our business, operations, clinical trials, supply chain, strategy, goals and anticipated timelines,
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 subsidiary, CLSN Laboratories, Inc., also a Delaware corporation.
Trademarks
The
Imunon brand and product names 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 ticker symbol “IMNN.”
Imunon
is a clinical-stage biotechnology company focused on advancing a portfolio of innovative treatments that harness the
body’s natural mechanisms with the aim to generate safe, effective and durable responses across a broad array of human diseases,
constituting a differentiating approach from conventional therapies. Imunon is developing its non-viral DNA technology across four modalities.
The first modality, TheraPlas®, is being developed for the coding of proteins and cytokines in the treatment of solid
tumors where an immunological approach is deemed promising. The second modality, PlaCCine®, is being developed for the
coding of viral antigens that can elicit a strong immunological response. This technology may represent a promising platform for the
development of vaccines in infectious diseases. The third modality, FixPlas®, concerns the application of Imunon’s
DNA technology to produce universal cancer vaccines, also called tumor associated antigen cancer vaccines. The fourth modality, IndiPlas®,
is in the discovery phase and will focus on the development of personalized cancer vaccines, or neoepitope cancer vaccines.
The
Company’s lead clinical program, IMNN-001, 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 durable levels, within certain safety
parameters, of powerful cancer-fighting molecules, such as interleukin-12 and interferon gamma, at the tumor site. Additionally, the
Company is conducting investigational new drug (“IND”)-enabling preclinical studies for the development of a COVID-19
booster vaccine (IMNN-101) and a treatment candidate for the Lassa virus (IMNN-102). The Company has also initiated preclinical work
to develop a Trp2 tumor associated antigen cancer vaccine in melanoma (IMNN-201). Imunon will continue to leverage these modalities
and to advance the technological frontier of plasmid DNA to better serve patients with difficult-to-treat conditions.
Technology
Platform
Imunon’s
technology platform is optimized 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 to the system,
a backbone with plasmid DNA or mRNA payload encoding therapeutic proteins, or pathogen antigens or tumor associated antigens or cancer
neoantigens 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 by chemically modifying the low molecular weight polymer
to improve its gene transfer activity without increasing toxicity. We believe that our non-viral DNA technology 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
biocompatibility of these polymers reduces the risk of adverse immune response, thus allowing for repeated administration. Compared to
naked DNA or cationic lipids, our delivery systems are generally more efficient, and cost effective and have a more favorable safety
profile. We believe that these advantages place Imunon in a position to capitalize on this technology platform.
THERAPLAS
MODALITY: IMNN-001 DEVELOPMENT PROGRAM
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 40 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% and 17%, respectively. First-line chemotherapy regimens are typically platinum-based combination
therapies. Although this first line of treatment has an approximate 80% response rate, 55% to 75% 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 bevacizumab are the only approved second-line therapies for platinum-resistant ovarian
cancer. The overall response rate for these therapies is 10% to 20% with median overall survival (“OS”) of 11 to 12 months.
Additionally, 10% to 15% of ovarian cancer cases nationwide are a result of germline or somatic BRCA mutations. With cognizance of tumor
genetics, practice has shifted to include targeted agents in ovarian cancer treatment.
Poly
(ADP-ribose) polymerase (“PARP”) enzymes are responsible for detecting and repairing single-stranded and double-stranded
DNA breaks during cell replication. BRCA1/2 mutations hinder the homologous recombination repair pathway, and tumor cells utilize PARP
enzymes to repair DNA. For this reason, these tumors are particularly sensitive to the mechanism of PARP inhibitors. PARP inhibitors
have expanded treatment options in ovarian cancer, but few treatment options are left for women who are not eligible to receive PARP
inhibitors.
Immunotherapy
is an attractive, novel approach for the treatment of ovarian cancer particularly since ovarian cancers are considered immunogenic tumors.
Interleukin-12 (“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
Immunotherapy
IMNN-001
is a DNA-based immunotherapeutic drug candidate for the localized treatment of ovarian cancer by intraperitoneally administering an 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
1 Study. In February 2015, we announced that the U.S. Food and Drug Administration (“FDA”) accepted the Phase I dose-escalation
clinical trial of IMNN-001 in combination with the standard of care in neoadjuvant ovarian cancer (the “OVATION 1 Study”).
On September 30, 2015, we announced enrollment of the first patient in the OVATION I Study. The OVATION 1 Study was designed to:
● attempt to define an optimal dose for a follow-on Phase I/II study.
In
addition, the OVATION 1 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:
During
2016 and 2017, we announced data from the first 14 patients in the OVATION 1 Study. On October 3, 2017, we announced final translational
research and clinical data from the OVATION 1 Study.
Key
translational research findings from all evaluable patients were 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 14 patients who completed treatment in the OVATION 1 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
1 Study showed positive results in progression-free survival (“PFS”). The hazard ratio (“HR”) was 0.53 in the
intent-to-treat (“ITT”) group, showing strong signals of efficacy. In its March 2019 discussion with the Company, the FDA
noted that preliminary findings from the Phase Ib OVATION 1 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 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 PFS results from the OVATION 1 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 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 NACT and IMNN-001
cycles. Under the current standard of care, in women with Stage III/IV ovarian cancer undergoing NACT, their disease progresses within
about 12 months on average. The results from the OVATION 1 Study supported 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 in the OVATION 1 Study. 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 1 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 was designed with a single dose escalation phase to 100 mg/m2 to identify a
tolerable dose of IMNN-001 within certain safety parameters while maximizing an immune response. The Phase I portion of the study would
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 would receive IMNN-001 plus chemotherapy pre- and post-interval debulking
surgery (“IDS”). The OVATION 2 Study was designed to 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 was 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 would be conducted after at least 80 events had been observed or after all patients had been followed for at least
16 months, whichever was 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 was designed to combine IMNN-001,
the Company’s IL-12 gene-mediated immunotherapy, with standard-of-care NACT. Following NACT, patients would undergo IDS, followed
by three additional cycles of chemotherapy.
IMNN-001
plus standard-of-care 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”) had recommended that IMNN-001 be designated as an orphan medicinal product for the treatment of ovarian cancer.
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 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 were in the treatment arm and 14 were in the control. Of the 34 patients enrolled in the trial,
27 patients have had their IDS with the following results:
● 80% of patients treated with IMNN-001 had a R0 resection.
● 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 was satisfactory, with an acceptable risk/benefit, and that patients tolerated IMNN-001 during a course of treatment that would
last up to six months. No dose-limiting toxicities were reported at this point in the OVATION 2 Study. Interim clinical data from patients
who had undergone IDS showed that the IMNN-001 treatment arm was continuing to show improvement in R0 surgical resection rates and CRS
3 chemotherapy response scores over the control arm. 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.
In
April 2023, the Company presented a poster at the American Association for Cancer Research Annual Meeting Demonstrating Preclinical Immune
Response of IMNN-001. The findings from a mouse model of peritoneally disseminated ovarian cancer suggested biweekly dosing regimen for
further evaluation in human clinical studies. This research in mice would underpin the dosing frequency being investigated in the Phase
I/II combination study with IMNN-001 and bevacizumab following NACT in advanced ovarian cancer.
In
September 2023, the Company announced interim PFS and OS data with IMNN-001 in its Phase I/II OVATION 2 Study. Interim clinical data
from the ITT population showed efficacy trends in PFS, demonstrating a delay in disease progression in the treatment arm of approximately
33% compared with the control arm, with the hazard ratio nearing the required value. Preliminary OS data follows a similar trend, showing
an approximate 9-month improvement in the treatment arm over the control arm.
Subgroup
analyses showed patients treated with a PARP inhibitor (“PARPi”) as maintenance therapy had longer PFS and OS if they were
also treated with IMNN-001 compared with patients treated with NACT only. This was not a pre-specified subgroup as PARP inhibitors were
approved after the OVATION 2 Study was initiated.
While
the data are still preliminary, the Company believes that patients treated with a combination of NACT + PARPi + IMNN-001 appear to have
the greatest benefit and should be the focus of on-going follow-up.
Imunon
also continues to see benefits in other secondary endpoints including an approximately 20% higher R0 tumor resection score and a doubling
of the CRS 3 chemotherapy response score to approximately 30% in the treatment arm versus 14% in the control arm. Chemotherapy response
score is considered a good prognostic indicator in ovarian cancer. The DSMB determined that safety analyses continue to show good tolerability
of IMNN-001 in this setting. Topline results from the OVATION 2 Study are expected in mid-2024.
IMNN-001
in Combination with bevacizumab. 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, announced
the commencement of patient enrollment in a collaboration to evaluate IMNN-001 in combination with bevacizumab in patients with advanced
ovarian cancer in the frontline, neoadjuvant clinical setting.
This
Phase I/II 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
are being randomized 1:1 in a two-arm trial. In October 2023, the first patient began treatment at University of Texas MD Anderson Cancer
Center in the Phase I/II Clinical Trial Evaluating IMNN-001 in Combination with Bevacizumab in Advanced Ovarian Cancer. The trial’s
primary endpoint is detection of minimal residual disease (MRD) by second look laparoscopy (SLL), and the secondary endpoint is PFS.
Initial SLL data are expected within one year following the completion of enrollment and final PFS data are expected approximately three
years following the completion of enrollment. This trial will also include a wealth of translational endpoints aimed at understanding
the clonal evolution and immunogenomic features of the MRD phase of ovarian cancer that is currently undetectable by imaging or tumor
markers.
PLACCINE
DNA VACCINE MODALITY: IMNN-101
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 modality (“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 modality is characterized by a single mono-cistronic or multi-cistronic DNA plasmid vector expressing single or
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 (“HHS”), to consider 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 4°C to 25°C, 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 indicate that the quality of the immune response as opposed to its absolute magnitude is what dictates
SARSCoV-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 have 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:
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 demonstrated 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 4°C and above, and to
facilitate cheaper and easier manufacturing.
On
January 31, 2022, the Company announced the initiation of a nonhuman primate (“NHP”) challenge study with Imunon’s
DNA-based approach for a SARS-CoV-2 vaccine. The NHP pilot study followed 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 a favorable safety profile 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 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 has demonstrated 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 six
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.
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 demonstrated 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 have a favorable safety profile 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 supported 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 NHP study involving three vaccine-treated non-human primates. The final data
were consistent with the earlier data and showed excellent immunological response and viral clearance. More specifically, in this NHP
study, we examined PLACCINE activity against a 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 demonstrated continued drug stability at 4° C (standard refrigerated
temperature).
In
March 2023, these compelling data were presented at the Vaccine Technology Summit 2023 in Boston. They showed robust immunogenicity and
protection in SARS-CoV-2 models, durable cellular or humoral responses detectable for more than 12 months, comparable protection activity
to a commercial mRNA vaccine in a booster-dose comparison and superior immune quality versus the mRNA vaccine in a single-dose comparison.
In
March 2023, the Company filed with the FDA a pre-IND package in advance of beginning human testing of a SARS-CoV-2 seasonal booster vaccine.
In July 2023, the FDA confirmed in a written response our plug and play strategy agreeing that a platform approach to pre-clinical toxicology
testing with reference to updated SARS-CoV-2 genes that align with current variant of concern may be used without additional need for
toxicology studies. This demonstrated the flexibility and versatility of our platform, which allows for the rapid production and development
of any vaccine by simply changing the antigen coding cassette.
The
Company announced on March 13, 2024 that it has submitted an IND application for a Phase I/II trial with IMNN-101, a seasonal COVID-19
booster vaccine, following positive feedback from the FDA. Development of our PlaCCine modality reached important milestones with confirmation
of its value across pathogens of interest by demonstrating the immunogenicity and safety of our vaccines in animals. The Company has
generated compelling data in SARS-CoV-2 and with IMNN-101, a next-generation COVID-19 seasonal booster, and expects to begin patient
enrollment in a Phase I/II trial in the second quarter of 2024.
During
the third quarter of 2023, the Company chose the Lassa virus as a pathogen target of interest for its PLACCINE modality. In August
2023, the Company announced it had entered into a Cooperative Research and Development Agreement (“CRADA”) with the
National Institute of Allergy and Infectious Diseases (“NIAID”) to evaluate the immunogenicity and efficacy of two
Imunon DNA-based Lassa virus vaccine candidates. Under the three-year agreement, the NIAID will assess the efficacy of PlaCCine DNA
constructs against Lassa virus in guinea pig and non-human primate disease models, including both prime and prime-boost vaccine
strategies.
This
collaboration with the Laboratory of Virology at NIAID to research a potential solution for combatting this life-threatening pathogen
will evaluate the hypothesis that a DNA-based vaccine may be an excellent modality for a Lassa virus vaccine. With its durable antigen
expression, longer shelf-life at workable, standard refrigerated temperatures and flexible manufacturing, the Company believes that PlaCCine
is a potentially superior alternative that can address the limitations of current commercial products particularly in developing countries
around the world.
This
CRADA is an example of one of the Company’s growth strategy pillars, namely, to help defray development costs through non-dilutive
sources of capital. Incremental investments to generate novel vaccine designs with optimized antigens will allow Imunon to quickly generate
early pre-clinical and clinical data against additional pathogen targets that position the Company to partner with large vaccine companies
who Imunon expects may fund remaining clinical development.
During
the fourth quarter of 2023, the Company updated data related to IMUNON’s PlaCCine SARS-CoV-2 DNA vaccine, including studies showing
PlaCCine expresses spike proteins in mice and primates demonstrating induction of spike-specific neutralizing antibody responses and
CD8 and CD4 spike-specific cellular responses. The induced immune responses in vaccinated mice were maintained for up to 14 months after
vaccination. Research being presented also shows that in both primates and mice, the induced immune responses reduced lung viral loads
by more than 90%. In mouse studies, robust immune responses were observed following a single intramuscular injection of either PlaCCine
SARS-CoV-2 DNA vaccine or a novel PlaCCine Lassa Virus DNA vaccine.
The
Company is eager to advance the FixPlas and IndiPlas modalities into universal and personalized cancer vaccines and have begun preclinical
work in melanoma. The Company’s consultants will provide invaluable assistance as we advance along the development pathway and
into clinical testing. The FixPlas concerns the application of our DNA technology to produce universal cancer vaccines also called tumor
associated antigen cancer vaccines. The IndiPlas modality is in the discovery phase and will focus on the development of personalized
cancer vaccines or neoepitope cancer vaccines.
THERMODOX®
- DIRECTED CHEMOTHERAPY
OPTIMA
Study
The
OPTIMA Study was designed to (i) evaluate ThermoDox® in combination with a first line therapy, radiofrequency ablation (“RFA”),
for newly diagnosed, intermediate stage HCC patients and (ii) enroll up to 550 patients globally at approximately 65 clinical sites in
the U.S., Canada, the European Union (“EU”), China and other countries in the Asia-Pacific region. The primary endpoint for
the OPTIMA Study was OS, and the secondary endpoints were progression free survival and safety. The statistical plan called for two interim
efficacy analyses by an independent Data Monitoring Committee (“DMC”).
BUSINESS
STRATEGY AND DEVELOPMENT PLAN
We
have not generated and do not expect to generate any revenue from product sales in the next several years, if at all. An element of our
business strategy has been to pursue, as resources permit, the research and development of a range of drug candidates for a variety of
indications. We may also evaluate licensing products from third parties to expand our current product pipeline. This is intended to allow