UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
☒ ANNUAL REPORT UNDER SECTION 13 OR 15(d)
OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended: December 31, 2024
☐ TRANSITION REPORT UNDER SECTION 13 OR 15(d)
OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from ____________ to
____________
Commission file number: 001-38793
INMUNE BIO INC.
(Exact name of registrant as specified in its charter)
225 NE Mizner Blvd, Suite 640
Boca Raton, FL33432
(Address of principal executive offices)(Zip Code)
(858)964 3720
(Registrant’s telephone number, including
area code)
Securities registered pursuant to Section 12(b)
of the Act:
Title of each class Trading Symbol Name of Market Where Traded
Common Stock ($0.001 par value) INMB 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 checkmark 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, 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 Exchange Act). Yes ☐ No ☒
The aggregate market value of the registrant’s
common stock held by non-affiliates of the registrant was approximately $135 million as of the last business day of the registrant’s
most recently completed second fiscal quarter (June 30, 2024), based upon the closing sale price for the registrant’s common stock
on that day as reported by The Nasdaq Capital Market. For purposes of this computation only, all executive officers and directors have
been deemed affiliates.
As of March 27, 2025, there are 22,930,311 shares
of common stock, $0.001 par value per share, outstanding.
DOCUMENTS INCORPORATED
BY REFERENCE
Certain information in Part III of this Annual
Report on Form 10-K is incorporated by reference to our definitive Proxy Statement for the 2025 Annual Meeting of Shareholders to be filed
with the Securities and Exchange Commission within 120 days after the fiscal year ended December 31, 2024.
FORM 10-K
FOR THE YEAR ENDED DECEMBER 31, 2024
TABLE OF CONTENTS
Item Number and Caption Page
Forward-Looking Statements ii
PART I 1
1. Business 1
1A. Risk Factors 29
1B. Unresolved Staff Comments 54
1C. Cybersecurity 54
2. Properties 54
3. Legal Proceedings 54
4. Mine Safety Disclosures 54
6. [Reserved] 55
7A. Quantitative and Qualitative Disclosures About Market Risk 66
8. Financial Statements and Supplementary Data F-1
9A. Controls and Procedures 67
9B. Other Information 67
9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 67
PART III 68
10. Directors, Executive Officers, and Corporate Governance 68
11. Executive Compensation 68
13. Certain Relationships and Related Transactions, and Director Independence 68
14. Principal Accounting Fees and Services 68
Signatures 73
i
PART I
All brand names or trademarks appearing in
this report are the property of their respective holders. Unless the context requires otherwise, references in this report to “INmune
Bio” the “Company,” “we,” “us,” and “our” refer to INmune Bio Inc., a Nevada corporation.
FORWARD-LOOKING STATEMENTS
This Annual Report on Form
10-K (this “Annual Report”) contains “forward-looking statements” Forward-looking statements reflect our current
view about future events. When used in this Annual Report, the words “anticipate,” “believe,” “estimate,”
“expect,” “future,” “intend,” “plan,” or the negative of these terms and similar expressions,
as they relate to us or our management, identify forward-looking statements. Such statements include, but are not limited to, statements
contained in this Annual Report relating to our business strategy, our future operating results and liquidity and capital resources outlook.
Forward-looking statements are based on our current expectations and assumptions regarding our business, the economy and other future
conditions. Because forward–looking statements relate to the future, they are subject to inherent uncertainties, risks and changes
in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking
statements. They are neither statements of historical fact nor guarantees of assurance of future performance. We caution you therefore
against relying on any of these forward-looking statements. Important factors that could cause actual results to differ materially from
those in the forward-looking statements include, without limitation, our ability to raise capital to fund continuing operations; our ability
to protect our intellectual property rights; the impact of any infringement actions or other litigation brought against us; competition
from other providers and products; our ability to develop and commercialize products and services; changes in government regulation; our
ability to complete capital raising transactions; and other factors (including the risks contained in the section of this Annual Report
entitled “Risk Factors”) relating to our industry, our operations and results of operations. Actual results may differ significantly
from those anticipated, believed, estimated, expected, intended or planned.
Factors or events that could
cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We cannot guarantee
future results, levels of activity, performance or achievements. Except as required by applicable law, including the securities laws of
the United States, we do not intend to update any of the forward-looking statements to conform these statements to actual results.
ii
PART I
Item 1. Business
Our Strategy
Our objective is to develop
and commercialize our product candidates to treat diseases where the innate immune system is dysfunctional causing or contributing to
the patient’s disease. Innate immune dysfunction can occur for a variety of reasons including genetics, lifestyle, and other factors.
However, age plays a significant role in the development of immune dysfunction. Innate immune dysfunction can be seen in cancer where
Natural Killer (“NK”) cells are impaired and facilitate a tumor’s evasion of the immune system and subsequent disease
progression. Chronic inflammation is implicated in neurologic and metabolic diseases where it impairs the innate immune system. Our initial
focus continue to be treatment of cancer with INKmune and Alzheimer’s Disease (“AD”) and Treatment Resistant Depression
(“TRD”) with XPro1595. We have added CORDStrom, a pooled, human umbilical cord mesenchymal stem cell (“HucMSC”)
product to treat recessive dystrophic epidermolysis bullosa (“RDEB”), a pediatric orphan disease caused by mutations in the
COL7A1 gene that results in a debilitating disease of skin blistering, dysphagia and failure to thrive with chronic wound problems that
often results in fatal squamous cell carcinoma.
XPro1595 (“XPro”),
targets Alzheimer’s Disease and TRD. XPro for AD has completed Phase I trials and a Phase II trial has completed enrollment of patients
at clinical sites in the United Kingdom, EU, Australia and Canada. Patients are currently being treated with XPro for Early AD as part
of that clinical trial. TRD is being prepared for Phase II trials. We expect to start a pivotal global registration trial in patients
with AD after the results of the Phase II trial have been analyzed. The INKmune program is in an open label Phase II trial in metastatic
castrate resistant prostate cancer (“mCRPC”). CORDStrom for the treatment of children with RDEB has completed a pivotal blinded
randomized cross-over trial. The data will be submitted for a marketing authorization (“BLA”) in the US in the next 12-18
months.
The overall principal components
of our business strategy to achieve these objectives are to:
Pursue development and
regulatory approval pathways. We believe INKmune and XPro may be approvable under pathways that are potentially shorter than those
typically available for drug products based on novel active ingredients, including as an orphan drug under the Orphan Drug Act and approval
under the Food and Drug Administration (the “FDA”) Accelerated Approval Program (see the section entitled “Government
Regulation”). We have not yet had a discussion with the United Kingdom Medicines and Healthcare Products Regulatory Agency (“MHRA”)
and/or FDA regarding such designation, but plan to do so in the future. We believe the INKmune program to treat castration resistant prostate
cancer may qualify for orphan status. We believe that it would take a minimum of six months to receive Orphan Drug status once we
apply for application and a minimum of 12 months to receive a designation once we submit an application. We might never have these discussions,
submit applications under the Orphan Drug Act or the FDA Accelerated Approval Program or have these applications approved if we do. We
have received Orphan Drug Designation (“ODD”) and Rare Pediatric Disease Designation (“RPDD”) for CORDStrom to
treat patients with epidermolysis bullosa (“EB”). We plan to file for Biologics License Application (“BLA”), an
approval document for full approval of CORDStrom with the FDA in late 2025 or early 2026. We also plan to file for Marketing Authorization
Application in the EU and United Kingdom in 2026 with CORDStrom for RDEB. Likewise, we plan to apply for an accelerated approval pathway
for the use of XPro to treat patients with AD in 2025.
1
Adopt a two-pronged patent
strategy. We are pursuing a two-pronged product development strategy that will seek to solidify our existing IP to prevent competition
and expand our IP suite into related therapeutic areas. We are confident that our core in-licensed IP (see the section entitled “Intellectual
Property”) and IP generated by the Company will allow us both freedom-to-operate and provide robust protection from outside competition
across all of our drug platforms. We will continue to invest in expanding our patent suite. We will also seek to further strengthen our
IP position by looking to in-license IP related to our focus on the innate immune system. All of our products are biologic products eligible
for Biologic Exclusivity after first approval. In the US, Biologic Exclusivity currently allows for 12 years of marketing exclusivity.
Provide clear value propositions
to third-party payors to merit reimbursement for our product candidates. We are designing our clinical development programs to demonstrate
compelling, competitive advantages to patients and prescribers, and to demonstrate value propositions to third-party payors. We believe
the use of INKmune patients with a high risk of tumor progression and death from tumor should safely prolong survival, improve the patient’s
quality of life and decrease the total cost of care for patients with these lethal malignancies. For example, cancer patients relapse
frequently. Each relapse requires a complex treatment regimen that has decreasing benefits. Treatment with INKmune as an out-patient may
provide a more durable remission and limit the need for treatment-associated hospitalizations. At the patient level, we believe INKmune,
if approved, should improve survival and quality of life. At the payor level, we believe INKmune, if approved, should provide more predictable
costs and outcomes. Additional therapies are need for treatment of Alzheimer’s disease are needed for medical, societal and economic
reasons. The cost of Alzheimer’s disease to the government is large and growing. Recently approved therapies that target amyloid
have a modest impact on disease progression and are difficult to use due to side-effects in some patients. The cost of AD to families
and care givers is real and burdensome. We believe treatment of dementia patients with XPro, including Alzheimer’s disease, may
provide a strategy to alter the costly dynamic of this disease in society today. RDEB is a lethal and debilitating disease in children
that requires life-long care-giver and medical support. Available therapies for the diseases focus on wound closure. Itch, a clinical
symptom that occurs in all children with RDEB, is considered by patients to be the most important symptom with no therapy. CORDStrom decreases
itch considerably and safely, improves quality of life and may improve wound healing.
Collaborate to maximize
the value of our technology. We believe there are two reasons for us to enter collaborations with other companies. The first is the
further development of INKmune, XPro and CORDStrom by either providing additional innovations to the product, including combination therapy
strategies, and/or providing resources to improve the speed and breadth of the development process. The second is to optimize the commercialization
of our products either globally or regionally. The ideal partner will benefit us in both ways.
We have leveraged our unique
capabilities to optimize clinical application of cell medicines by developing CORDStrom for the treatment of RDEB. We believe that we
have developed a way to manufacture human mesenchymal stromal cells for the medical research and biotech community that offers large
volumes of high-quality, human umbilical cord mesenchymal stromal cells with minimal batch-to-batch variability. We have established
a reliable supply of human umbilical cords based on our agreement with the Anthony Nolan Cord Blood Bank in the United Kingdom and plan
to seek additional supplies from US sources in the future. We have developed a validated manufacturing process that reliably produces
clinical grade (“cGMP”) quality mesenchymal stromal cells that we call CORDStrom. The manufacturing process is currently
performed by INmune Bio staff at a contract manufacturing site under the direction of Mark Lowdell, the Company’s CSO. We supplied
CORDStrom for a multicenter academic clinical trial in in children with RDEB. This pivotal trial was sponsored by the Great Ormond Street
Children’s Hospital (“GOSH”) in London treating children with intermediate and severe- RDEB. The results of the pivotal
trial show that CORDStrom therapy decreases itch and pain and improves clinical scores in patients with RDEB. We have entered an exclusive
global license with GOSH for the clinical data. The Company plans to combine the clinical data and manufacturing process into a regulatory
dossier that seeks marketing authorization in the US via a BLA and in the United Kingdom and EU by MAA in 2026 or earlier if possible.
The program has received an ODD and RPD and may be eligible for a Priority Review Voucher if product approval occurs by September 26,
2026. The Company plans to seek scientific advice from the FDA, MHRA and EMA on the program during 2025 in preparation for regulatory
submissions. The regulatory path for therapeutic applications of the mesenchymal stem/stromal cell products is well established and similar
to the regulatory approval process for other cellular medicines. We will only be responsible for regulatory compliance related to manufacturing
of the mesenchymal stromal cells when the product is being developed by a third party. When developing a therapeutic product for the
Company’s commercial portfolio, the Company will be responsible for all aspects of the regulatory process.
CORDStrom is a patent-pending
cell medicine comprising aseptic, allogeneic, pooled HucMSCs in suspension for injection or infusion. The CORDStrom platform leverages,
among other things, proprietary screening, pooling and expansion techniques to create off-the-shelf, allogeneic, pooled HucMSCs as medicines
to treat complex inflammatory diseases. CORDStrom products are designed to provide high-quality, off-the-shelf, batch-to-batch consistent,
scalable, cGMP manufactured, potent cellular medicines that can be produced at low cost and with repeatable specification independent
of donor characteristics. Initially developed at the INKmune manufacturing facilities utilizing United Kingdom academic grant funding,
CORDStrom is a mesenchymal stromal cell (“MSC”) product platform that shows promise as a first systemic therapy for potentially
treating RDEB and many other debilitating conditions. While the first generation CORDStrom product is agnostic to disease indication,
the platform enables creation of indication-specific products, which can be tuned for optimization of anti-inflammatory, immunomodulatory,
homing, and other characteristics.
The CORDStrom product platform
shares many similarities, including reagents, and procedures, with the Company’s INKmune oncology product, enabling the Company
to leverage economies of scale, experienced staff, and other resources to strategically manufacture both products in a rotational campaign
with resource and environmental efficiencies.
2
Overview of Immunotherapy for Cancer
The immune system has two
parts, innate and adaptive. The innate immune system is the body’s first line of defense against an infection, providing immediate,
non-specific responses to eliminate harmful cells in the body. Components of the innate immune system include cytokines, chemokines, macrophages,
neutrophils and NK cells, among others.
The adaptive immune system
is often initially triggered by the innate immune system, mounts a delayed response against diseased cells and plays a role protecting
against re-infection. An adaptive immune response is highly specific to a pathogen or antigen and is developed or learned from prior exposure.
Key components of the adaptive immune system include antibodies which bind to antigens and mark them for destruction by other immune cells,
B-cells which produce these antibodies upon exposure to antigens, and T-cells which attack and eliminate the diseased cells.
The biopharmaceutical industry
has made significant advances in harnessing specific components of innate and adaptive immune systems for therapeutic use. Some of these
approaches are summarized below.
Cytokines. Tumor
Necrosis Factor alpha (“TNF”) is the focus of XPro and INB03. TNF biology has four elements that include two cytokines, soluble
TNF and trans-membrane TNF (“sTNF” and “tmTNF,” respectively), and two receptors, TNF Receptor 1 and 2 (“TNFR1”
and “TNFR2”). The biology of TNF ligation of TNFR varies dramatically based on what elements of the TNF system that are used.
sTNF binding to TNFR1 is responsible for inflammation and cell death while sTNF binding to TNFR2 promotes proliferation of regulatory
T cells (“Treg”). In patients with advanced cancers, increased sTNF is not favorable to long-term survival because it promotes
epithelial-mesenchymal transformation and metastasis while making the tumor microenvironment more immunosuppressive promoting resistance
to therapy. In the CNS, sTNF promotes neuronal cell death, demyelination and synaptic pruning while tmTNF promotes nerve cell survival,
improves synaptic function and stimulates remyelination. In brief, sTNF is the “bad” TNF and tmTNF is the “good”
TNF. In patients with cancer, infection or neurologic disease, blockade of tmTNF function has negative consequences such as immunosuppression,
increased infection, synaptic dysfunction and demyelination.
One of the early applications
of immunotherapy is the use of cytokines, including interferons and interleukin-2 (“IL-2”). Interferons are molecules that
inhibit the growth and replication of diseased cells and stimulate innate immune cells to attack them. They have been used as standard
of care for hepatitis B and C and multiple sclerosis, and to a lesser extent, as treatment for certain cancers, including chronic myeloid
leukemia, cutaneous T-cell lymphoma, myeloma and non-Hodgkin’s lymphoma. However, the use of interferons has generally decreased
over the years due to serious adverse events (e.g., flu-like symptoms and dramatic weight loss) and introduction of new therapies
with higher efficacy, better safety profiles and more convenient administration although Alpha-interferon remains the treatment of choice
for some hematological conditions such as polycythemia. IL-2 activates T-cells and NK cells to attack diseased cells. IL-2 has been used
to treat select cancers, but due to its relatively poor safety profile, physicians often only resort to this therapy for the most advanced
settings.
Antibody therapy.
Antibodies exist in three formats: monoclonals (“mAbs”), oligo/polyclonal and antibody-drug conjugates. mAbs represent an
effective therapeutic modality and are important to the treatment paradigm of various diseases. Drug manufacturers have leveraged mAbs’
ability to induce an antibody-dependent cell-mediated cytotoxicity, or ADCC effect to develop better treatments that prolong survival
and quality of life of patients. In addition, mAbs designed to inhibit specific checkpoints in the immune system have overcome in vivo
immune suppression and the resulting immune responses have led to profound therapeutic benefit in some patients. However, the degree of
efficacy of these therapies is heavily reliant on the immune system of patients, many of whom are severely immuno-compromised. In addition,
mAbs are manufactured through a complex process that requires purification of cell products created from a cell line. Polyspecific antibodies,
for example bi-specific antibodies, are able to target more than one antigen. These are often used to bring and effector T cell in contact
with a target cell. Antibody drug conjugates are mAbs attached to a toxin, chemotherapy or radio therapy that delivers the cancer killing
payload directly to the cancer.
3
Dendritic Cell Therapies.
This approach is designed to indirectly stimulate a patient’s T-cells by leveraging the role of dendritic cells in presenting antigens
to T-cells. Cancer vaccines are the most common application of dendritic cells. FDA-approved dendritic cell therapies such as PROVENGE,
which entails collecting monocytes from the patient, maturing them into dendritic cells, “loading” ex vivo with the
patient’s cancer antigens, and then re-infusing in the patient. Currently, this process is cumbersome and expensive, and again,
relies on an intact and effective immune system of the patient. There are additional ongoing preclinical studies and clinical trials being
conducted by our competitors aimed at addressing certain of the limitations associated with this approach. To date, current clinical results
of dendritic cell therapies have been mixed.
CAR-T and TCR Therapies.
T-cells recognize diseased cells by receptors engaging with antigens that are present on or inside the diseased cells. CAR-T therapy entails
genetically engineering T-cells to express synthetic CARs that direct T-cells to antigens on the surface of cancer cells. TCR therapy
modifies T-cells to express high-affinity tumor specific TCRs that recognize intra-cellular antigens that must be presented on the surface
of target cells. In early clinical trials, CAR-T and TCR therapies have demonstrated impressive anti-tumor activity in a narrow spectrum
of hematologic cancers and garnered significant attention by research institutions and biopharmaceutical companies. We believe a key limitation
of adaptive autologous immunotherapy is the need to retrieve non-compromised immune cells from a cancer patient which requires a complex
and costly manufacturing process to develop the therapy. The complexity of this personalized process is reflected in the price of the
two approved therapies. CAR-T therapies - tisagenlecleucel and axicabtagene ciloleucel for advanced leukemia and lymphoma respectively.
The cost of a single therapy is many hundreds of thousands of dollars. As a consequence of this need to harvest active T-cells, current
Phase I clinical trials for autologous CAR-T cell therapy in large part enroll patients from highly selected, often relatively early-stage
disease in a narrow spectrum of cancers, including bulky hematological cancers. In addition, Phase I clinical trials of CAR-T cell immunotherapy
have reported severe adverse toxicities of cytokine release syndrome and neurotoxicity, requiring hospitalization, pre-conditioning and,
in some instances, intensive care unit admission following side effects associated with cytokine release syndrome. As a result, though
our competitors continue to develop their CAR-T and TCR product candidates with the goal of addressing certain of the limitations associated
with these approaches, we believe these serious challenges may limit their potential and use in a variety of indications, including solid
tumors.
Checkpoint Inhibitors.
Immune cells express proteins that are immune checkpoints that control and down-regulate the immune response. These are best defined
in T lymphocytes and include PD-1, CTLA-4, TIM-3 and LAG3. Tumor cells express the ligands to these receptors. When T cells bind the ligand
to these proteins on the tumor cells, the T cell is turned off and does not attempt to attack the tumor cell. Thus, checkpoint inhibitors
(“CPI”) are part of the complex strategy used by the tumor to evade the patient’s immune system and are responsible
for resistance to immunotherapy. Biopharmaceutical companies have successfully developed CPI that block the receptor/ligand interaction
to promote the adaptive immune response to the tumor. Six CPI are currently approved, pembrolizumab, nivolumab, atezolizumab, avelumab,
durvalumab, and ipilimumab for a wide variety of solid tumors including melanoma, lung, bladder, gastric cancers and others. More CPI
are in development and more tumor types will be added to the list of sensitive tumors over the next years. CPI have become the backbone
of cancer therapy and are expected to be the best -selling class of drugs in the future.
NK Cells. NK
cells typically represent approximately 2% to 13% of circulating lymphocytes and are a critical component of the immune system responsible
for innate immunity. Unlike adaptive immune cells, they are ever present and ready to attack, having the inherent ability to detect and
eliminate diseased cells without the need for antigen presentation, which is why they are called “natural killers.”
NK cells bind to stress ligands
expressed by the diseased cells and directly eliminate them. This binding induces NK cells to release cytokines, including interferons
and GM-CSF, which are integral in recruiting additional innate and adaptive immune responses by the host. NK cells also represent a critical
effector cell for ADCC, whereby target cells bound with human antibodies, whether made by the patient’s body or administered, are
selectively destroyed by the NK cells.
4
Our Innate Immune Dominant-Negative
TNF (“DN-TNF”) product candidate
XPro1595, XPro or Pegipanermin
was originally licensed from Xencor.
XPro neutralizes sTNF in the
brain without affecting tmTNF or TNF receptors. Soluble TNF is a cause of the destructive neuroinflammation in the brain are microglial
and astroglial cells (“glial cells”). Glial cell are two of four cells in the neural unit that also includes oligodendrocytes
and nerve cells. Activated microglial cells are considered the resident macrophages of the brain. The primary role of microglial cells
is to protect the neural unit from infection. When innate immune dysfunction causes chronic inflammation, activated microglial cells produce
soluble TNF that activates astrocytes. Activated glial cells cause nerve cell and oligodrocyte dysfunction that results in synaptic pruning,
nerve cell death and demyelination of neurons. These pathologies contribute, in part, to neurodegenerative diseases such as AD, Parkinson’s
disease, ALS, MS, Huntington’s disease, glaucoma and TBI (traumatic brain injury) may contribute to neuropsychiatric diseases such
as depression, bi-polar disease, sleep disorders, autism, schizophrenia and PTSD. In the setting of AD, microglial activation causes synaptic
dysfunction and nerve cell death that contributes to cognitive decline and the behavioral manifestations of AD including depression, aggressiveness,
sleep disorders, hallucinations and anhedonia. Elimination of microglial activation should reverse these symptoms. Because soluble TNF
is the apex cytokine in the inflammatory cytokine cascade, neutralization of soluble TNF with XPro should prevent glial activation and
normalizes function of the neural unit.
The Company has completed
a Phase I trial using XPro to reverse neuroinflammation in patients with Alzheimer’s disease. The trial was performed in Australia
and was partially funded by a $1M USD Part-the-Cloud Award from the Alzheimer’s Association. The clinical trial was the first in
the Company’s development program for the treatment of dementia. The open label, dose escalation trial in patients with Alzheimer’s
disease with biomarkers of peripheral inflammation (one of CRP>1.5mg/L, HgbA1c>6.0, ESR>10sec or have ApoE4) treats the patients
with XPro as a once-a-week subcutaneous injection for 3 months. AD patients with one biomarker of inflammation are classified as having
AD with neuroinflammation (“Adi”). The company estimates this group of patients includes at least 40% of patients with AD.
Patients have multiple biomarkers of neuroinflammation tested before and during therapy including soluble biomarkers in blood and cerebral
spinal fluid, behavioral biomarkers (neuropsychiatric symptoms of AD), EEG and neuroimaging biomarkers using MRI. The primary goal of
this short, open label study was to demonstrate that treatment with XPro decreases neuroinflammation safely and to define the dose of
XPro to use in the Phase II trial.
The Company has enrolled a
global blinded randomized Phase II trial in ADi patients with Early AD in Australia, Canada, the United Kingdom, Spain, France, Germany,
Poland, the Czech Republic, and Slovakia. Early AD is patients that have Mild Cognitive Impairment or mild AD. There is an Expanded Access
Scheme in patients who completed the Phase I trial in Australia that can request XPro of which two patients from the Phase I remain on
the drug as of this writing. The goal of the Phase II trial will be to demonstrate the prolonged control of neuroinflammation in patients
with dementia will help control cognitive decline.
5
The Phase I trial enrolled 18 patients at three
dose cohorts of 0.3, 0.6 and 1.0mg/kg given once a week as subcutaneous injection for three months. Patients in the 1.0mg/kg group were
offered extended use of the drug for up to 12 months. Three patients remained on XPro for 12 months. Preliminary data was presented in
a webinar on 13 July 2020. Additional data was presented on January 21, 2021CSF cytokine/chemokines were measured in 9 patients before
and after 12 weeks of weekly therapy with XPro using a panel from OLINK Target 48 Cytokine (Figure below).
In the 6 patients in the 1mg/kg
per week dose, only one cytokine and chemokine, interferon gamma (“INFg”) did not change in the CSF of patients, the remainder
all decreased on average of 15%. The data analyzed provides evidence that XPro decreases neuroinflammation in patients with Alzheimer’s
disease.
We believe these data support
the use of XPro to treat other diseases where neuroinflammation is a part of the pathophysiology of the disease. The company studied the
consequences of decreasing neuroinflammation in the 6 patients from target dose group (XPro 1mg/kg for 12 weeks) be looking at the CSF
proteome using technology for Proteome Sciences using their TMT CalibratorTM platform. A large data set of proteins were identified.
Early analysis of the data focusing on 26 AD related proteins demonstrated changes in inflammation, neuronal and synaptic proteins caused
by decreasing neuroinflammation after treatment with XPro (Figure below). The proteome also demonstrated a clear dose response with a
greater number of proteins being affected by the target dose compared to low dose XPro therapy (0.3 vs 1.0 mg/kg/week for 12 weeks) (Figure
below). The CSF proteome data is only partially analyzed. Additional data may result from these ongoing analytics.
6
The results of the Phase I
study demonstrated that XPro safely decreases neuroinflammation in patients with AD and elevated neuroinflammation with biomarkers of
peripheral inflammation or are ApoE4 positive when given for at least 3 months at the 1mg/kg once a week dose. Decreasing neuroinflammation
with XPro appears to decrease neurodegeneration and improve synaptic function and promote remyelination. The effect of XPro on the biology
and immunology of the brain in patients with AD suggest XPro therapy in patients with peripheral biomarkers of inflammation or ApoE4 allele(s)
may impact cognitive decline. Although there were anecdotes of improved cognitive function in patients receiving the target dose of XPro,
this cannot be verified because the trial was not a blinded, randomized trial. The impact on cognition of controlling neuroinflammation
with XPro will be studied in the Phase II program which is a blinded randomized, placebo controlled clinical trial.
AD02 is the ongoing blinded
randomized global Phase II trial in patients with early AD enrolled 208 patients in a 2:1 ratio (XPro:placebo) at 1mg/kg once a week.
The trial enrolled the last patient in November 2024. Patients are treated for 6 months of therapy. The primary end-point is Early/Mild
Alzheimer’s Cognitive Composite (“EMACC”), a sensitive cognitive end-point validated for use in patients with early
AD. Secondary cognitive (CDR-SB and NPI) and functional (GAS, ADCS-ADL) end-points will be measured. Exploratory structural and function
biomarkers of brain function and structural integrity using EEG and MRI DTI will be used in some or all patients. Top line cognitive data,
EMACC, will be presented around June of 2025. All additional cognitive, functional, neuroimaging and biomarker data will be presented
approximately 8 weeks later.
Effective therapy for TRD
is a large unmet need. Twenty percent of patients with a Major Depressive Disorder have TRD. Once third of TRD patients have peripheral
biomarkers to inflammation (elevated CRP). This is a large patient population. The role of TNF and anti-TNF therapeutics was explored
in a small open label clinical trial by Prof. Andrew Miller, MD of Emory University whereby it was demonstrated that patients which have
elevated TNF levels responded to treatment with infliximab (Miller, 2011).
The blinded, randomized Phase
II trial will use biomarkers of peripheral inflammation to select patients with TRD for enrollment. Patients will be treated for 6 weeks.
Primary endpoints include both clinical and neuroimaging measures.
XPro, is delivered as a subcutaneous
injection, similar to an insulin treatment or anti-obesity GLP-1 drugs, is given once a week. More frequent treatment cannot be ruled
out for future indications. Because this is a simple subcutaneous injection similar to an insulin injection (the therapy patients give
themselves for treatment of Type 1 diabetes mellitus), we expect patients to administer the therapy by themselves or caregivers and not
require expensive or logistically challenging clinic visits to receive the therapy.
7
Release of XPro drug supply
GMP DN-TNF product (XPro)
used in the oncology Phase I, AD Phase I and COVID-19 Phase II trial were manufactured by Lonza at a site in New Hampshire. The supply
of Lonza DN-TNF product is limited but allowed completion of the Phase I study in Alzheimer’s disease and support of patients in
the extension study for 12 months. New batches of XPro have been produced for ongoing clinical trials. The Company engaged KBI Biopharma
to manufacture 6 lots of XPro at the Boulder, Colorado facility using the original master cell bank and updated manufacturing process.
One lot has been converted into drug product using the US fill/finish facility of Vetter Pharma. Half of the first lot is frozen as drug
substance at -80C with a plan to convert to drug product as clinical supplies are needed to support the AD and TRD Phase II trials. The
unfrozen drug product is being used in the ongoing AD02 AD trial. The remainder of the original fermentation runs is frozen as a cell
paste with a plan to process to drug substance. The company expects to convert the drug substance to drug product during 2025. Downstream
processing to drug product and fill/finish to drug product of the cell paste will occur in 2025 as needed to support the clinical trials.
We plan to use a two-step approach to improve the yield of the drug substance from the fermentation process. The Company is working on
the yield of the drug product using the existing E.coli-based system. A second program is focused on down-stream process improvements
in the drug manufacturing program. Once the new strain and process is validated and functional, we will perform a manufacturing campaign
drug for future clinical trials. In the future, the Company may consider a strain change to improve yield of the fermentation step further.
The decision for strain improvements and strain change will be made in the future as clinical development programs proceed.
Interaction with Regulatory Authorities Regarding
XPro Development
We have completed a Phase
I trial with DN-TNF in oncology. At this time we do not plan additional clinical trials with DN-TNF in oncology. A Phase II trial with
XPro in patients with Alzheimer’s disease is underway. Dosing of patients in the Phase II trial will complete in May 2025. The Phase
I trial with XPro in patients with Alzheimer’s disease was performed in Australia under the regulatory authority of the TGA using
the Clinical Trials Exemption (“CTX”) scheme. Our first interaction with the regulatory body occurred in March 2018. The Company
received approval to initiate the Phase I trial in patients with advanced solid tumors on May 21, 2018. The second interaction with
the regulatory body occurred in March 2019. The Company received approval to initiate the Phase I trial with XPro in patients with
Alzheimer’s disease in May 2019 and received authorization to start the Phase II trial in patients with mild AD on January 5, 2022.
Our first interaction with the FDA occurred in July 2020 as part of the Phase II Quellor program to treat respiratory failure in patients
hospitalized with COVID-19 infection. The newly manufactured XPro is being used to support the Phase II AD trial, the TRD Phase II trial
and the Expanded Access Scheme.
8
XPro Regulatory Strategy
Drugs from the DN-TNF platform
will be developed using adequately powered, well designed studies with the goal to demonstrate a meaningful clinical benefit to patients.
Beyond Phase I, these will most often be blinded, randomized clinical trials using validated end-points that have been authorized by a
regulatory authority – the FDA, TGA, MHRA, EMA, Health Canada, etc. Currently, all planned studies will be performed in North America,
Australia, EU and/or the United Kingdom. Because there are no therapies similar to XPro approved in any market, we plan to take advantage
of the regulatory opportunities afforded to therapies that treat markets with a high unmet need. In the U.S., this includes Orphan Drug
Designation and expedited programs for approval including Accelerated Approval, Breakthrough Therapy Designation, Fast Track Designation,
and priority review (see the section entitled “Government Regulation”). We cannot predict which, if any, of these programs
we will benefit from without further discussions with the FDA, EMA and other competent regulatory authorities.
Immunotherapy for Treatment of Alzheimer’s Disease
XPro is being developed for
the treatment of Alzheimer’s disease. Microglial activation and neuroinflammation are important causes of the synaptic dysfunction
and nerve cell death that causes cognitive decline in patient with dementia and Alzheimer’s disease. The relationship between β
amyloid plaques and tau neurofibrillary tangles, the traditional targets in AD drug development and neuroinflammation is complex. We believe
targeting plaques and tangles will have limited benefit. Targeting neuroinflammation, the common pathway leading to synaptic dysfunction
and nerve cell death, may be an effective treatment strategy. Substantial pre-clinical data supports the use of XPro in murine models
of AD. Substantial indirect data supports use of XPro in humans including a decreased risk of AD in patients treated with non-selective
TNF inhibitors for rheumatoid arthritis and treatment using direct injection into paraspinous venous plexus. Because of different mechanism
of action of XPro compared to the non-selective TNF inhibitors, we expect a lower risk of immunosuppression and demyelinating complications
such as multiple sclerosis (“MS”). The Company reported preliminary data on July 13, 2020 and January 21, 2021 supporting
the use of XPro to decrease neuroinflammation in patients with Alzheimer’s disease and biomarkers of peripheral inflammation (see
above).
We completed enrollment of
patients into an open label, biomarker directed, Phase I clinical trial in Australia that approaches AD as an immunologic disease. Patients
with dementia with the diagnosis of AD with biomarkers of chronic inflammation that includes at least one of a hs-CRP>1.5 mg/L, a ESR>10
mm/h, a HbgA1C>6.0% or are ApoE4 positive were treated with XPro for 12 weeks. Three dosing cohorts were preformed – 0.3, 0.6
and 1.0 mg per week as a subcutaneous injection. Patients had multiple inflammatory biomarkers test before therapy, at 6 weeks and at
12 weeks. Biomarkers were reported in blood and cerebral spinal fluid. Experient biomarkers including MRI measures of white matter tract
neuroinflammation, axonal quality and axon myelin, and MRI measures of gray matter quality were included. Cognitive end-points were not
the focus of the Phase 1 clinical trial because of the wide range of disease severity enrolled and lack of a placebo group. Patients enrolled
in the Phase I trial had MMSE ranging from 24 to 12. This wide range of disease severity at the time of enrollment and the lack of a blinded
concurrent control group did not allow for determination of cognitive benefit beyond several anecdotal reports. The first patient was
enrolled in the low dose 0.3mg/kg/week cohort in the last week of November 2019. The Safety Review Committee met by teleconference on
January 7, 2020, to review the course of the patients in the first cohort and voted to open the second cohort, 1.0mg/kg/week, to enrollment.
The first patients were enrolled in the cohort the second week of February 2020. Based on preliminary data released on July 13, 2020,
and January 21, 2021, we closed after completion of a 0.6mg/kg treatment group. We canceled plans to treat patients with 3.0mg/kg. The
data from the Phase I trial informed the design of the Phase II trials described above. Mindful, the blinded randomized placebo control
trial in patients with Early AD began enrollment in 2022. The final patient was enrolled in the trial in November 2024. Top line cognition
data will be available June 2025. Patient enrollment criteria included one inflammatory biomarker plus and MMSE between 27 and 22. During
the 6 month trial, patients received XPro or placebo once-a-week by subcutaneous injection. Two-thirds of the patients were randomized
to XPro. Overall, 56% and 44% of the 208 patients had mild AD and MCI, respectively.
XPro Registration Studies and/or Partnering
We plan to aggressively pursue
an efficient registration strategy using XPro to improve the lives of patients with ADi. We define ADi as Alzheimer’s disease with
biomarkers of inflammation. We believe ADi is not the only indication for XPro in neurodegenerative and neuropsychiatric diseases. We
plan to pursue other indications in neurodegenerative diseases as resources become available. We have received NIMH funding to support
a Phase II TRD program that will start patient enrollment during 2025. We have an active partnering position as it relates to XPro development
in neurodegenerative and neuropsychiatric diseases, although limited partnering discussions are underway at this time. There are two partnering
opportunities with this novel immunotherapy for the treatment of neurologic and psychiatric diseases. The first is a traditional partnership
focused on the developing the drug for all neurodegenerative and neuropsychiatric applications. The second is a more focused partnership
developing XPro as part of a combination therapy for a company’s existing therapy. After completion of proof-of-concept Phase II
studies, we will decide what the most efficient registration strategy is available to the company with XPro.
9
INKmune: Our NK cell Directed Product Candidate
INKmune is our product candidate that converts the patient’s resting
NK cells into cancer memory like NK cells, an essential step to allow them to participate in the immune control of the patient’s
cancer. We have shown this works ex vivo in human tissue cell cultures, and we believe that this will work in vivo which is the purpose
of our planned clinical trials.
Cancers grow and relapse because
they evade the immune system. In many cancers, NK cells are the most important cell for the elimination of residual disease that causes
cancer relapse. NK cells target cells based on a series of complex antigens on the cancer cell surface that signal the NK cells to activate
and kill the cancer cell. NK cells develop a memory like NK cell phenotype to enhance killing of cancer cells. This phenotype requires
multiple simultaneous signals to be delivered to the NK cells. A cocktail of three cytokines, IL12, IL15 and IL18 can be used to convert
a resting NK cell to cytokine induced memory like NK cells (“CIML”) [Fehneger 2016] or by INKmune priming with INB16 (TpNK
– tumor primed NK cells). Although the intracellular biology of these two strategies has yet to be worked out, they do not appear
to be identical. In summary, INKmune converts resting NK cells into tumor killing memory like NK cells that function well in the hostile
environment of the TME. (Figure 1 below).
10
The ability of NK cells to
kill tumor cells depends on the strength and duration of the cell-cell interaction. This is called avidity. The higher the avidity the
greater the tumor cell killing. Cytokine stimulation may increase avidity of NK binding to some cancer cells whereas, in all experiments
to date, INKmune priming enhances NK binding to all cancer cells tested. The relative increase in avidity to specific cancer cells is
cytokine specific; as shown below, IL15 increases NK avidity for the ovarian cancer line SKOV-3 whereas IL2 has a limited effect. IL15
primed NK cells lyse SKOV-3 cells whereas IL2 primed NK do not. INKmune primed NK (TpNK) showed the highest avidity for the tumor cells
and the highest level of cytotoxicity. It is likely that the use of multiple cytokines will achieve the same level of avidity and cytotoxicity
as INKmune but studies with multiple cytokines have not yet been performed (Figure below).
We have demonstrated TpNK killing of many tumor types in laboratory studies.
Tumor priming is effective regardless of the source of the NK cells (normal volunteers or patients with cancer) and in many types of tumors
– both cell lines and primary tumors from patients. The principle of TpNK killing has also been demonstrated in two Phase I trials
in patient with acute myelogenous leukemia (“AML”). These trials were not supported by us and used a first-generation personalized
cell therapy product and treatment strategy that is different from the INKmune product and treatment strategy. In these trials, haplo-identical
NK cells obtained from a first degree relative by leukapheresis were primed ex-vivo using a lysate of the parent cell line from which
we derived INB16 - INKmune. Once the TpNK therapy has been produced and passed quality testing, the patient received conditioning therapy
with chemotherapy (cyclophosphamide and fludarabine), the primed haplo-identical NK cells were given to patients by intravenous infusion.
Two Phase I clinical trials have been performed using that first-generation adoptive cell therapy treatment strategy. An investigator-initiated
trial performed at the Royal Free Hospital in London 2009 was funded by a United Kingdom charity. Fifteen patients with relapsed, high-risk
AML were enrolled in the trial. Because of drop-out due to disease progression, delays in product production and complications of conditioning
therapy, only 7 of the fifteen patients were treated with the TpNK cell product. Four of seven patients showed clear benefit from the
treatment with the TpNK product with prolonged relapse free remission and, in one patient, conversion of a partial remission to full remission.
None of the remissions were durable; all patients ultimately died from disease progression. The safety of the product was found to be
a combination of toxicity from the chemotherapy/radiotherapy conditioning regimen and the TpNK therapy. In general, the complications
were well tolerated although did require medical intervention including prolonged periods of aplasia in two heavily pretreated patients
that resolved with supportive care. The results of this study have been published in a medical journal (PLoS One. 2015 Jun 10;10(6):e0123416.
doi: 10.1371/journal.pone.0123416. eCollection 2015). In 2013, a second open label, multi-center trial was performed in the US using the
same product and procedures but targeting a slightly different patient population. In the second trial, 12 patients in first remission
with AML were treated with the haplo-identical TpNK product produced using the first generation ex-vivo priming process. After conditioning
with chemotherapy alone, the patients received TpNK in three dosing cohorts – 3x10^5, 1x10^6 or 3x10^6 TpNK per kilogram. Patients
were followed for safety and relapse free survival. This trial confirmed the safety of the TpNK treatment in patients with AML and reinforced
many of the efficacy findings seen in the first trial with none of the previously experienced side effects. Patients benefited from haplo-identical
TpNK therapy with prolonged relapse free survival including two patients that remain in remission more than 42 months after treatment.
This trial has been published. (Biol Blood Marrow Transplant. 2018 Mar 26. pii: S1083-8791(18)30132-0. doi: 10.1016/j.bbmt.2018.03.019.)
The results of the laboratory and Phase I studies provide evidence that our strategy for treating residual disease is sensible but unproven.
11
Because INKmune primes NK cells to target naturally occurring antigens,
we believe INKmune can be used to treat a wide variety of cancers including hematologic malignancy (AML, MM, CML, high risk MDS) and solid
tumors (renal, prostate, breast, ovarian, pancreas and lung). We expect the list of INKmune sensitive tumors to continue to expand.
The primary role for INKmune
will be an immunotherapy targeting residual disease in patients after debulking cancer therapies such as cytotoxic chemotherapy and surgery.
At this time, we plan to give INKmune as monotherapy. We do not rule out the possibility of using INKmune as part of combination therapy
in the future. We do not expect to need to modify INKmune to treat these additional types of cancer, because we believe INKmune is a universal
cancer therapy where “one size fits all”. We believe for INKmune to receive regulatory approval for each cancer indication,
clinical trials will need to be performed which demonstrate its safety and effectiveness as a treatment for each such cancer. We believe
the difficulty and cost of achieving these labels extensions will decline with each successive approval, if and when achieved. For example,
if INKmune is proven to be effective therapy in patients with castration resistant prostate cancer, we will need to perform separate pivotal
trials for approval in lung, prostate or renal cancer.
Three step process to preparation for INKmune
human clinical trials:
INKmune GMP scale-up for Phase I/II clinical
material
The working cell banks and
individual INKmune product to be used in the patients for the clinical trial have been produced at the Centre for Cell, Gene & Tissue
Therapeutics at Royal Free Hospital / University College London to full cGMP (MHRA MIA(IMP)11149). All manufacturing has been under the
direction of Professor Mark Lowdell. The Company can produce enough INKmune to complete its Phase I clinical trial in men with metastatic
castrate resistant prostate cancer (“mCRPC”). We have validated storage of INKmune for up over 3 years in vapor phase nitrogen
and have a fully scalable, closed system manufacturing process in validation which can produce up to 6 patient doses per week during phase
I and II trials. At intermediate scale we can manufacture 40 doses per week in a single 15-liter bioreactor. Importantly, we have validated
the storage of INKmune at -80oC for up to 27 days which greatly facilitates the delivery and local storage of the drug for
clinical trials and post commercialization use. In contrast, as far as we know all other NK cell therapies and T cell therapies require
complex shipping of drug products in vapor phase nitrogen below -150oC and specialized arrangements for ongoing storage at
the clinical sites. We may need additional INKmune for future clinical trials.
Interaction with Regulatory Authorities Regarding
INKmune Development
The INKmune Phase I studies in high-risk MDS were performed in the United
Kingdom and Greece. We met with the Medicines and Healthcare Products Regulatory Agency (“MHRA”), the United Kingdom version
of the FDA as part of a Scientific Advice Meetings in preparation for submitting the CTA for our first planned program. During March 2024,
the Company decided to terminate further enrollment in the MDS trial due to recruitment difficulties in the European trial sites.
12
INKmune Product Development Path Proposed Phase
I Study in patients with high-risk MDS
During 2021, we initiated
an open label Phase I cancer study in patients with high-risk myelodysplastic syndrome (“MDS”). The first patient was enrolled
in the first quarter of 2021. In the Phase I trial, we planned to treat patients with detectable residual disease in bone marrow and/or
peripheral blood (<15% blasts by conventional tests) with intravenous infusions of INKmune and monitored for changes in peripheral
blood NK activation, NK function and changes in residual blast counts in blood and bone marrow. We and others have previously shown that
MDS patients with inadequate NK function have statistically significantly poorer prognosis than matched patients with normal levels of
NK function (Tsirogianni et al 2019) and we have shown in laboratory experiments that the functional activity of NK cells from MDS patients
can be enhanced by exposure to INKmune. Moreover, INKmune-primed NK cells are not inhibited by the hypoxic conditions of the diseased
bone marrow microenvironment.
The first patient was treated in the second quarter of 2021. The patient,
part of the first cohort, received 1x10^8 INKmune cells on day 1,8 and 15 as an in-patient. The patient did not require any type of conditioning
therapy or cytokine support. The patient tolerated the three infusions without any problems. The patient underwent intensive monitoring
over 120 days. There are 4 observations from this first patient. The patient has dramatically increased the number of activated, “memory-like”
NK cells in circulation. Memory-like NK cells (mlNK) are activated NK cells with a unique cell surface protein phenotype and which show
enhanced lysis of tumor cell in vitro. Post treatment with INKmune, elevated levels of mlNK cells were present in the patients in the
peripheral blood for more than 119 days when trial follow-up ceased. The patient mlNK actively kill NK resistant cancer targets in vitro.
Finally, the patient had a significant clinical improvement with a reduction of his ECOG score from 2 to 0 and a significant reduction
in blood product support.
Three compassionate use cases have also been treated. Two were young patients
with AML who had failed previous hematopoietic stem cell transplants (“HSCT”). The first compassionate-treatment patient showed
such improved neutrophil and platelet counts that she was discharged from hospital for the first time in six months. The second patient
treated compassionately had failed two high risk HSCT and entered the course of INKmune therapy with high percentage of blasts in his
bone marrow. His blood NK cells responded in differentiation into mlNK as hoped but it is too early to determine if INKmune has provide
any clinical benefit. Due to market opportunities, the Company closed the high-risk MDS trial to focus on solid tumors. The Company plans
to put all of its INKmune development efforts into the on-going US Phase I/II trial in men with mCRPC.
13
INKmune Registration Studies and/or Partnering
During March 2023 the Company
opened an Investigational New Drug (“IND”) application for a Phase I/II trial of INKmune in mCPRC. The clinical trial is an
open label Phase I/II trial in men with metastatic castrate resistant prostate cancer. The trial has a modified Baysian design that allows