UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
For
the fiscal year ended December 31, 2024.
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 $10.8 million as of June 28, 2024
(the last business day of the Registrant’s most recently completed second fiscal quarter) based on the closing sale price of $1.16.
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, 2024, were excluded. This determination of executive officers and directors as affiliates is not necessarily
a conclusive determination for any other purpose.
As
of February 21, 2025, 14,620,732 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 2
Ovarian Cancer Overview 2
IMNN-001 Immunotherapy 3
OVATION I Study 3
OVATION 2 Study 5
PLACCINE DNA VACCINE TECHNOLOGY PLATFORM 8
COVID-19 Vaccine Overview 9
Our Next Generation Vaccine Initiative 9
BUSINESS STRATEGY AND DEVELOPMENT PLAN 11
RESEARCH AND DEVELOPMENT EXPENDITURES 13
GOVERNMENT REGULATION 13
MANUFACTURING AND SUPPLY 24
SALES AND MARKETING 24
PRODUCT LIABILITY AND INSURANCE 24
COMPETITION 24
INTELLECTUAL PROPERTY 26
Patents and Proprietary Rights 26
EMPLOYEES 27
COMPANY INFORMATION 27
AVAILABLE INFORMATION 27
ITEM 1A. RISK FACTORS 27
ITEM 1B. UNRESOLVED STAFF COMMENTS 43
ITEM 1C. CYBERSECURITY 43
ITEM 2. PROPERTIES 43
ITEM 3. LEGAL PROCEEDINGS 44
ITEM 4. MINE SAFETY DISCLOSURES 44
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. RESERVED 46
Overview 46
Business Plan 46
Financing Overview 48
Critical Accounting Policies and Estimates 49
Results of Operations 50
Financial Condition, Liquidity and Capital Resources 52
Off-Balance Sheet Arrangements 53
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 53
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 53
ITEM 9A. CONTROLS AND PROCEDURES 53
ITEM 9B. OTHER INFORMATION 54
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 54
PART III
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 54
ITEM 11. EXECUTIVE COMPENSATION 59
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 69
PART IV
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 70
1. FINANCIAL STATEMENTS 70
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 (“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 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
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 its modalities. The first modality, TheraPlas®,
is 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 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
Company’s lead clinical program, IMNN-001, is a DNA-based immunotherapy for the localized treatment of advanced ovarian cancer
that has completed Phase II development studies. 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 has entered into
a first-in-human study of its COVID-19 booster vaccine (IMNN-101). We 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 or 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, we believe that our delivery systems are generally more efficient, 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 more than 60% of women dying within five years of diagnosis.
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. With
the five-year survival rates for Stages III and IV at 41% and 20%, respectively, there remains a need for a therapy that not only reduces
the recurrence rate but also meaningfully improves overall survival. 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 clinical 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 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”). 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 Solutions, a subsidiary of Dassault Systèmes, 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.
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 the time of 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 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 15
patients in the Phase I portion and up to 95 patients in Phase II. The sample size is consistent with a Phase II trial designed to inform
the design of a Phase III trial comparing IMNN-001 with neoadjuvant + adjuvant chemotherapy versus neoadjuvant + adjuvant chemotherapy
alone. As a Phase II study, the OVATION 2 Study was not powered for statistical significance. The primary endpoint is PFS and the 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. Additional endpoints included objective response rate, chemotherapy response score, and surgical response.
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 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 correlate 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 had 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 had completed enrollment
with 113 patients. 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 followed
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.
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.
In
June 2024, the Company announced database lock for the OVATION 2 Study. At that time, median OS and PFS had been reached, and all patients
in the open-label study had achieved treatment observation duration of 16 months, as required by protocol to evaluate efficacy. On July
11, 2024, a scientific advisory board with DSMB members, principal investigators, and scientific experts was held to review efficacy
and safety data from the OVATION 2 study.
On
July 30, 2024, the Company announced positive topline results from the Phase II OVATION 2 Study. Highlights from patients treated with
IMNN-001 plus standard-of-care in a first-line treatment setting include:
The
PFS results, the trial’s primary endpoint, support the OS results with:
● A three-month improvement in PFS compared with standard-of-care alone.
These
initial results from the OVATION 2 Study were presented in a late-breaking session at the Society
for Immunotherapy of Cancer (SITC) 39th Annual Meeting in November 2024.
On
September 11, 2024, a scientific advisory board was held with DSMB members, principal investigators, and scientific experts to discuss
and seek input on the protocol synopsis for the Phase III trial. A protocol synopsis was submitted along with a briefing document for
review and input at the End-of-Phase II (“EOP2”) meeting with the U.S. Food and Drug Administration focused on the Phase
III study. The EOP2 meeting was conducted in the fourth quarter of 2024.
In
December 2024, the Company announced additional clinical data from ongoing analyses of results from the Phase 2 OVATION 2 Study. The
updated results, based on an additional seven months of patient monitoring, showed the hazard ratio (HR) decreased from 0.74 to 0.69
in the ITT population, with an increase in median overall survival (OS) from 11.1 to 13 months following treatment with IMNN-001 plus
standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (NACT) versus SoC alone. More than one-third of patients in the trial survived
more than 36 months from the point of study enrollment, with 62% of those surviving patients from the IMNN-001 treatment arm and 38%
from the SoC arm. Over 10% of trial participants have reached 48 months or beyond.
The
Company plans to present full OVATION 2 Study results at an upcoming medical conference and to submit the results for publication in
a peer-reviewed medical journal. The Phase 3 trial is anticipated to begin in the first quarter of 2025.
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.
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.
As
of December 31, 2024, twelve patients were enrolled in the Phase I portion of this study at the University of Texas MD Anderson Cancer
Center. Memorial Sloan Kettering Cancer Center and John Hopkins Medicine Sidney Kimmel Cancer Care Center have been added as a clinical
site for this study.
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, 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 development 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
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 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 the 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. The presentation entitled: “Novel DNA Approaches for Cancer Immunotherapies and Multivalent
Infectious Disease Vaccines” highlighted the Company’s technology platform.
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 (“PoC”) 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). These compelling data were presented at the Vaccine Technology Summit 2023 in Boston in March 2023. 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.
On
April 18, 2024, the Company announced that it received clearance from the FDA to begin a Phase I clinical trial with a seasonal COVID-19
booster vaccine. The Company filed an Investigational New Drug (IND) application for IMNN-101 in late February. The primary objectives
of the Phase I study are to evaluate safety, tolerability, neutralizing antibody response, and the vaccine’s durability (duration
of immunogenicity) in healthy adults. Secondary objectives of the study include evaluating the ability of the IMNN-101 vaccine to elicit
binding antibodies and cellular responses and their associated durability. The Phase I study enrolled 24 subjects to evaluate three escalating
doses of IMNN-101. For this study, IMMN-101 has been designed to protect against the SARS-CoV-2 Omicron XBB1.5 variant, in accordance
with the FDA’s Vaccines and Related Biological Products Advisory Committee’s June 2023 announcement of the framework for
updated COVID-19 doses. Based on these results, we will advance discussions with potential partners to continue development of the platform.
During
the second quarter of 2024, the Company announced that DM Clinical Research in Philadelphia was the first clinical site activated for
patient recruitment for its Phase I study with IMNN-101 in a seasonal COVID-19 vaccine. DM Clinical Research is an integrated national
network of clinical trial sites focused on delivering advanced, preventive medicine to underserved communities. As of September 2024,
all 24 Phase I participants were inoculated with IMNN-101 at DM Clinical Research. Topline safety and immunogenicity data are anticipated
in the first half of 2025.
The
Phase I trial is designed to establish PoC for IMNN-101 as an advancement in vaccine technology. At the conclusion of this trial, Imunon
intends to seek partnership and/or business development opportunities to develop the scientific and business case for IMNN-101 as a future
vaccine to address viral mutations.
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
us to diversify the risks associated with our research and development expenditures. To the extent we are unable to maintain a broad
range of drug candidates, our dependence on the success of one or a few drug candidates would increase and would have a more significant
impact on our financial prospects, financial condition, and market value. We may also consider and evaluate strategic alternatives, including
investment in, or acquisition of, complementary businesses, technologies, or products. Drug research and development is an inherently
uncertain process and there is a high risk of failure at every stage prior to approval. The timing and the outcome of clinical results
are extremely difficult to predict. The success or failure of any preclinical development and clinical trial can have a disproportionately
positive or negative impact on our results of operations, financial condition, prospects, and market value.
Our
current business strategy includes the possibility of entering into collaborative arrangements with third parties to complete the development
and commercialization of our drug candidates. In the event that third parties are contracted to manage the clinical trial process for
one or more of our drug candidates, the estimated completion date would largely be under the control of that third party rather than
us. We cannot forecast with any degree of certainty which proprietary products or indications, if any, will be subject to future collaborative
arrangements, in whole or in part, and how such arrangements would affect our development plan or capital requirements. We may also apply
for subsidies, grants or government or agency-sponsored studies that could reduce our development costs. However, we cannot forecast
with any degree of certainty whether we will be selected to receive any subsidy, grant or governmental funding.
As
of December 31, 2024, the Company had $5.9 million in cash and cash equivalents to fund its operations. The Company’s primary sources
of cash have been proceeds from the issuance and sale of its common stock, including via its at-the-market (“ATM”) program
and other potential funding transactions. There can be no assurance that the Company will be able to do so in the future on a timely
basis on terms acceptable to the Company, or at all. The Company has not yet commercialized any of its product candidates. Even if the
Company commercializes one or more of its product candidates, it may not become profitable in the near term. The Company’s ability
to achieve profitability depends on several factors, including its ability to obtain regulatory approval for its product candidates,