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, 2021
☐ 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)
INMUNE BIO INC.
David Moss
225 NE Mizner Blvd, Suite 640
Boca Raton, FL33432
Phone: (858)964 3720
(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 ($.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. ☐
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 $157 million as of the last business day of the registrant’s
most recently completed second fiscal quarter (June 30, 2021), based upon the closing sale price for the registrant’s common stock
on that day as reported by the NASDAQ Capital Market. Shares of common stock held by each officer and director of the registrant on
June 30, 2021 have been excluded in that such persons may be deemed to be affiliates.
As of March 3, 2022, there are 17,863,095 shares of common stock, $0.001
par value per share outstanding.
FORM 10-K
FOR THE YEAR ENDED DECEMBER 31, 2021
TABLE OF CONTENTS
Item Number and Caption Page
Forward-Looking Statements ii
PART I
1. Business 1
1A. Risk Factors 37
1B. Unresolved Staff Comments 60
2. Properties 60
3. Legal Proceedings 60
4. Mine Safety Disclosures 60
PART II
6. [Reserved] 61
7A. Quantitative and Qualitative Disclosures About Market Risk 72
8. Financial Statements and Supplementary Data 73
9A. Controls and Procedures 74
9B. Other Information 74
9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 74
PART III
10. Directors, Executive Officers, and Corporate Governance 75
11. Executive Compensation 75
13. Certain Relationships and Related Transactions, and Director Independence 75
14. Principal Accounting Fees and Services 75
PART IV
Signatures 79
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 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 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 not functioning normally and contributing to the patient’s disease. This can
be in cancer where Natural Killer (“NK”) cells are inactive and contribute to a tumor’s evasion of the immune system
and/or disease progression while expression of MUC4 and immunosuppressive cells of the tumor microenvironment proliferate to protect the
tumor from attack by the patient’s immune system or this can be other diseases such as neurologic and metabolic diseases where chronic
inflammation results in innate immune system dysfunction. Our initial focus will be the treatment of cancer, treatment of Alzheimer’s
Disease (“AD”), and the treatment of Treatment Resistant Depression (“TRD”). In cancer, we plan to pursue two
parallel development programs: (1) with INKmune we will initially focus on treating women with resistant disease relapse refractory ovarian
carcinoma and patients with high-risk myelodysplastic syndrome (high risk MDS); (2) with INB03, we will treat patients with cancers that
express MUC4, a mucinous polyglucan on the surface of some epithelial cancer cells, that appears to predict resistant to immunotherapy
including women with MUC4 expressing HER2+ breast cancer. Our third drug candidate XPro1595 (“XPro"), targets Alzheimer’s
Disease and TRD. XPro for AD has completed Phase I trials and is being prepared for Phase II trials. XPro for TRD is being prepared for
Phase II trials. During 2021, we closed our Phase II clinical trial for treatment of pulmonary complications due to COVID-19 infection
as the Company determined it was a high-risk, low reward program due to the development of vaccinations and therapies which were not available
when we started the clinical trial. The principal components of our strategy to achieve this objective are to:
Pursue development and
regulatory approval pathways. We believe INKmune, INB03 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 “Government Regulation”).
We have not yet had a discussion with the 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 MDS cancer program may qualify for orphan status. We believe
that it would take a minimum of six months to receive Orphan Drug status once we submit an 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 as the FDA Accelerated Approval Program or have these applications approved if we do.
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 “Intellectual Property”)
will allow us both freedom-to-operate and provide robust protection from outside competition. We will continue to invest in expanding
our patent suite. We will also seek to further to strengthen our IP position by looking to in-license IP related to our focus on the innate
immune system.
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 and/or INB03 in patients with a high risk of tumor progression and death from tumor should prolong survival, improve
the patient’s quality of life and decrease the total cost of care for patients with these lethal malignancies. For example, ovarian
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 and INB03 therapy, once approved, should improve survival and quality of life. At the payor level, we believe INKmune,
once approved, should provide more predictable costs and outcomes. Therapies for Alzheimer’s disease are needed for medical, social
and economic reasons. The cost of Alzheimer’s disease to the government is large and growing. The cost to families and care givers
is real and burdensome. We believe treatment of patients with dementia, including Alzheimer’s disease, may provide a strategy to
alter the costly dynamic of this disease in society today.
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, INB03 and XPro 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 continue to look for ways to utilize our unique capabilities to
optimize clinical application of cell therapies. We believe that we have identified a way to manufacture human mesenchymal stem cells
for the medical research and biotech community that offers large volumes of high-quality, low passage human umbilical cord mesenchymal
stem cells with minimal batch-to-batch variability. We believe this may solve the problem associated with supplying an adequate supply
of human mesenchymal stem cells for clinical applications. 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. We have developed a validated manufacturing process that reliably
produces contract manufacturer of the clinical grade (“cGMP”) quality mesenchymal stem cells that we call CORDstrom. The manufacturing
process can be performed at a contract manufacturing site under the direction of Mark Lowdell, the Company’s CSO. We will seek academic
laboratories and biopharma companies who need a reliable source of high quality pooled human umbilical cord mesenchymal stem cells for
research of and development of clinical products. Once identified, we plan to act as a cGMP for the development of therapeutic products
by utilizing contract manufacturers. Because the production of the product is not continuous, we do not expect to engage a contract manufacturer
until we have a customer identified. To date, we are supporting two academic clinical trials with CORDstrom. One program is a Phase 2
trial sponsored by the Great Ormond Street Children’s Hospital in the UK treating children with erythematous bullousa, a disfiguring
skin disease in children that is similar to a second degree burn and the second program is treatment of system lupus in adults. Both these
studies are ongoing. INmune Bio is supplying the clinical product for treatment of these patients. The Company does not know the results
of these trials until they are announced by the principle investigators at the clinical sites. We have identified contract manufacturers
in the UK that have the capability to produce cGMP stem cells. We expect the commercial arrangement with academic laboratories or biopharma
companies to be a combination of fee-for-service and licensing that does not require additional investment by us. We will be opportunistic
in pursuing therapeutic opportunities for our own portfolio with this platform in the future if resources become available. The regulatory
path for therapeutic applications of the mesenchymal stem cell products is well established and similar to the regulatory approval process
for other cell therapies. We will only be responsible for regulatory compliance related to manufacturing of the mesenchymal stem 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.
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. 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. Tumor Necrosis Factor alpha (“TNF”) is the focus of 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.
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. The only FDA-approved dendritic cell therapy is 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 by 2027.
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 product candidate
We renamed XPro, which
we license from Xencor, to INB03 when it is used for cancer related indications. We will continue to call the drug XPro when
used for treatment of neuropsychiatric diseases, including Alzheimer’s disease and TRD discussed below. INB03 and XPro are the
same drug with different names for marketing purposes. INB03 is a novel innate immune system check-point inhibitor that we believe
decreases expression of MUC4 by the tumor, an important resistance mechanism to immunotherapy, decreases proliferation of MDSC,
promotes recruitment of cytotoxic T cells to the TME and may convert immunosuppressive tumor macrophages into tumor phagocytic
macrophages. In murine models, these changes make the tumor reverse resistance to treatment with immunotherapy alone or in
combination with tyrosine kinase inhibitors (TKI) such a lapatinib. MUC4 expression is increased by sTNF. Resistance to trastuzumab
therapy by MUC4 expressing HER2+ breast and gastric cancer cells is driven by steric hinderance. By neutralizing sTNF with INB03,
MUC4 expression decreases allow trastuzumab to bind HER2/neu. The mechanism by which combination of INB03 with TKI improves efficacy
over TKI alone remains under investigation. By using INB03 as part of combination therapy for cancer, we believe the patient’s
dysregulated immune response, a hallmark of cancer progression and resistance to therapy, to be converted to a coordinated immune
response that can overcome resistance mechanisms to immunotherapy. These immune responses have been studied in at least two animal
models. In a murine model of an inflammatory cancer, where 3-methylcholanthrese is given to mice in a subcutaneous injection that
causes the development of multiple cutaneous fibrosarcoma. This model was developed by Y Akamatsu in 1967 while working at the
National Cancer Institute of the NIH. In research published by Professor Nikola Vujanovic in Cancer Immunology
Research in 2016, treatment with INB03 resulted in smaller and fewer cancers with increased survival. INB03 is an engineered
PEGylated protein that neutralizes human soluble TNF, a human inflammatory cytokine that is increased in patients with advanced
cancer. By specifically neutralizing the cytokine, there is decreased phosphorylation of STAT3, an essential step required for the
proliferation of the MDSC population, and secretion of the immunosuppressive cytokines. The combination of decreased MDSC
proliferation and decreased immunosuppressive cytokines allows the immune system to respond to the tumor. This data was published in
an article entitled Inhibition of Soluble Tumor Necrosis Factor Prevents Chemically Induced Carcinogenesis in Mice in Cancer
Immunology Research in Cancer Immunology Research 2016. In summary, INB03 functions as an innate immune system
checkpoint inhibitor by eliminating the population of MDSC that provides an immunosuppressive shield protecting the tumor, the
patient’s immune system is able to function normally to the benefit of the patient – it can attack the tumor. TNF plays
an important role in breast cancer (Schillaci R, Front. Oncol., 22 April 2020
| https://doi.org/10.3389/fonc.2020.00584). In a murine model of trastuzumab resistant breast cancer using JMIT-1 cells,
a human cell line of HER2 positive breast cancer resistant to trastuzumab placed into immunocompromised mice, INB03 downregulates
MUC4 from the surface of the JMIT-1 HER2+ breast cancer cells to allow the trastuzumab resistant cells to become trastuzumab
sensitive (Figure A from Bruni, NYAS 2020) to decrease tumor growth (from Schillaci SABCS 2018, Figure B). JMIT-1 cells are also
resistant to lapatinib, a TKI inhibitor used as a second line therapy in women with trastuzumab resistant HER2+ breast cancer. The
addition of INB03 to lapatinib in the animal model reverses lapatinib resistance in part by decreasing expression of MUC4 (from
Bruni NYAS 2020, Figure C). In addition to decreasing resistance to trastuzumab by decreasing MUC4 expression, INB03 decreases the
immunosuppressive tumor microenvironment (Schillaci SABCS 2018, Bruni NYAS 2020). Recently, Dr. Schillaci reported the MUC4
expressing triple negative breast (TNBC) cancer patients have a worse overall survival. (Schillaci SABCS 2021). These data may be
relevant to all tumors that express HER2 or MUC4 including upper gastrointestinal malignancies such as gastric and pancreatic
cancer. We believe MUC4 expression is a biomarker of resistance that may dictate changes therapeutic strategy by clinical teams
5
6
Because INB03 targets the
patient’s immune system and not the tumor, we believe INB03 is an immunotherapy that can be used to treat many types of hematologic
malignancies and solid tumors as part of combination therapy. The decision to use INB03 in a patient will be based on biomarkers that
should predict that a patient will benefit from treatment with the drug. We believe the ideal biomarker is easy to use and is determined
before treatment begins. MUC4 expression by epithelial tumors is an example of this type of biomarker. Our Phase I clinical trial preceded
the identification of MUC4 as a biomarker and focused on using INB03 as monotherapy. This is a typical Phase I clinical trial design for
first-in-man trials in cancer. We expect to use INB03 as part of combination therapy with approved cancer therapies as part of Phase II
development. We do not expect to need to modify INB03 therapy to treat each different type of cancer, because INB03 therapy targets the
immune system, not the cancer. We do expect to develop the INB03 beyond Phase II to target a specific type of cancer to meet the current
system of regulatory approval. For instance, INB03 may be approved to treat patients with HER2+/MUC4+ breast cancer. To get subsequent
approval for the treatment of patients with MUC4+ TNBC or MUC4+ pancreatic cancer, we will need to perform a pivotal trial in patients
with TNBC and pancreatic cancer respectively. After the first regulatory approval, if and when achieved, we believe the difficulty and
cost of achieving these labels extensions will decline with each successive approval. At this time, we cannot predict if patients without
biomarkers of inflammation, elevated MDSC or cytokines, or increased expression of MUC4 will benefit from treatment with INB03. Those
studies may be performed in the future, but they are not a priority.
XPro neutralizes soluble
TNF in the brain in exactly the same way INB03 neutralizes soluble TNF in the tumor microenvironment but the effects of soluble TNF neutralization
in the brain are different. The cause of the destructive neuroinflammation in the brain are microglial and astroglial cells. The glial
cell are two of four cells in the neural unit that also includes oligodentrocytes 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 dendritic pruning, 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.
7
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 is partially funded by a $1M USD Part-the-Cloud Award
from the Alzheimer’s Association. The clinical trial is 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. 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) and neuroimaging biomarkers using MRI. The primary
goal of this short, open label study is to demonstrate that treatment with XPro decreases neuroinflammation safely and to define the dose
of XPro to use in the Phase II trial. Studies of cognitive function are performed on the patients but are not expected to show significant
change because of the short duration of the trial and the wide range of disability in patients enrolled in the clinical trial (MMSE range:
24-12). The goal of the planned Phase II trial will be to demonstrate the prolonged control of neuroinflammation in patients with dementia
will help control cognitive decline. The Company plans two Phase II trials, one each in mild cognitive impairment (MCI) and mild AD.
The
trial enrolled 18 patients at doses of 0.3, 0.6 and 1.0mg/kg given once a week as subcutaneous injection for three months. Patients in
the 10mg/kg group were offered extended us 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. Neuroimaging data from six patients were presented in the figure below. In summary,
treatment with XPro at either 0.3 or 1.0mg/kg once-a-week as a subcutaneous injection (low and target dose respectively) decreased white
matter free water (WMFW) as measured by MRI. WMFW is a validated biomarker of neuroinflammation. Although the number of patients is low,
there was a dose response with a greater decrease in WMFW in the target dose compared to the low dose group. An analysis of inflammation
in white matter tracts demonstrated a significant decrease in WMFW (40%; range 20-52%) in the arcute fasciculus, a white matter tract
important in the control of language and short-term memory (Figure D). These data suggest XPro is decreasing neuroinflammation in patients
with Alzheimer’s disease who have biomarkers of peripheral inflammation.
8
Additional data was presented on January 21, 2021. The goal of the
January 21 data release was to show a correlation between the white matter free water, a novel biomarker of inflammation with cerebral
spinal fluid (“CSF”) cytokines and chemokine levels, a traditional measure neuroinflammation. CSF cytokine/chemokines were
measure in 9 patients before and after 12 weeks of weekly therapy with XPro using a panel from OLINK Target 48 Cytokine (https://www.olink.com/products/olink-target-48-cytokine/),
that measures 45 (Figure AD1).
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%. Using data from
all patients treated for 12 weeks (3 low dose, 6 target dose), a high correlation (R2=.7561) between the white matter free
water safe mask and the inflammation composite score is shown in figure AD2. The data analyzed provides evidence that XPro decreases neuroinflammation
in patients with Alzheimer’s disease.
9
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 (https://www.proteomics.com/services/tmtcalibrator-workflow). 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 AD3). 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 AD4). The CSF proteome data is only partially analyzed. Additional data may result from these ongoing analytics.
10
The results of the Phase I study demonstrates that XPro safely decreases
neuroinflammation in patients with AD who have 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 biologic characteristics suggests 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 programs.
The Company plans two Phase
II trials in patients with AD with biomarkers of inflammation. A blinded randomized trial in patients with mild AD plans to enroll 201
patients in a 2:1 ratio (XPro:placebo) at 1mg/kg once a week. Patients will be treated for 6 months. A patient enrichment strategy will
be used to ensure patients have neuroinflammation – patients must have at least two of elevated CRP, hemoglobinA1c, ESR or have
an ApoE4 allele. 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 (ADAS-Cog13, CDR-SB and NPI) and functional (GAS, ADCS-ADL) end-points will be
measured. Biomarkers of inflammation using white and gray matter analytics measured by MRI DTI similar to those used in the Phase I trial
will also be used. All patients will be eligible to continue on XPro for at least 6 additional months. Clinical and MRI metrics will be
followed during the extension trial.
The second Phase II trial will be a blinded randomized trial in patients
with MCI in which the Company plans to enroll 60 patients in two arms in a 2:1 ratio (1mg/kg/week XPro, placebo). Patients will be treated
for 3 months. Patients must have at least one ApoE4 allele to qualify for the trial. The primary end-point is EMACC, a sensitive cognitive
end-point validated for use in patients with early AD. Secondary clinical endpoints include the CDR-SB, Cogstate Battery, E-Cog, NPI,
and ADCS-ADL. Imaging endpoints of neuroinflammation (White matter free water), white matter integrity (apparent fiber density, radial
diffusivity), and gray matter quality (cortical disarray measurement) will be assessed via MRI. Changes in brain metabolism will be assessed
via FDG-PET. Additional secondary measures of function include EEG, and speech and language. All patients will be eligible to continue
on XPro for at least 9 additional months. Clinical and MRI metrics will be followed during the extension trial. The Company may
amend the clinical trial design from time-to-time to improve the quality of the data or the probability of success.
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 Company received a $2.9M
USD award from the National Institute of Mental Health (“NIMH”) to treat TRD with XPro. The blinded, randomized Phase II trial
will use a biomarkers of peripheral inflammation to select patients with TRD for enrollment. Patients will be treated for 6 weeks. Primary
end-points include both clinical and neuroimaging measures. The final trial design is ongoing and discussions with the FDA are not complete.
The Company anticipates receiving authorization to initiate the clinical trial in the second half of 2022.
INB03 and XPro are delivered
as a subcutaneous injection, similar to an insulin treatment, given one to three times per week. 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 to themselves and not require expensive or logistically challenging clinic visits to receive the therapy.
Three step process to preparation
for INB03 and XPro for human clinical trials:
Release of INB03 and XPro drug supply
GMP DN-TNF product (INB03 and XPro) are available for clinical development
after completion of release testing. The annual process for release testing was completed in February 2018, January 2019, December 2019
and November 2020. The supply of 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 future trials, new batches of XPro have been produced. The Company engaged KBI Biopharma
to manufacture 6 lots of XPro/INB03 at the Boulder, Colorado facility using the original master cell bank and updated manufacturing process.
Two lots have been converted into drug product using the US fill/finish facility of Vetter Pharma. Two of the lots are frozen as drug
substance at -80C with a plan to convert to drug product the second half of 2023. The final two lots are frozen as a cell paste with a
plan to process to drug substance in during 2023 or 2024 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. We hope to improve the yield of the drug product using the existing E.coli
based system. Once the new 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.
11
Interaction with Regulatory Authorities Regarding
INB03 and XPro Development
We have completed a Phase I trial with INB03 in oncology and a Phase
I trial with XPro in patients with Alzheimer’s disease. The Phase II program with Alzheimer’s disease will start first half
2022. The Phase I trial with XPro in patients with Alzheimer’s disease is 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 with INB03 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 COVID19 infection. We plan to complete the regulatory process for the Phase II clinical trials in
patients with Alzheimer’s disease and Phase II TRD clinical trials with the FDA during the first half of 2022.
INB03 Product Development Path: Proposed Phase
II Studies in patients with cancer
Phase I open label study in
patients with advance solid tumors has been completed. All future studies cancer will use INB03 as part of combination therapy. Based
on the results of the Phase I study and work performed and reported by Prof. Roxana Schillaci, we are planning a study of INB03 in combination
with currently approved second line therapy for treatment of tumors that express MUC4. This may include a study in women with trastuzumab
resistant HER2+ metastatic breast cancer where primary or secondary resistance to trastuzumab is common and may include women with brain
metastasis. Alternatively, the Phase II trial may include women with MUC4+ TNBC or patients with MUC4+/HER2+ gastric cancer or MUC4+ pancreatic
cancer. These trials will not be initiated until the COVID-19 pandemic has run its course. We do not expect to treat patients in an oncology
INB03 Phase II trial with INB03 before 2023. Pre-clinical studies of INB03 in MUC4 expressing tumors continue.
INB03 Registration Studies and/or Partnering
We plan to pursue an efficient
registration strategy using INB03 to improve the lives of patients with cancer and biomarkers of inflammation such as MUC4. We believe
that this strategy has use across many types of solid tumors including patients who have failed CPI, tyrosine kinase inhibitors (“TKI”)
and anti-cancer antibody therapy such as trastuzumab monoclonal antibodies and trastuzumab based antibody drug conjugates. We have an
active partnering position as it relates to INB03 development in cancer, although no partnering discussion are underway at this time.
We do not expect partnering discussions to begin until Phase II data demonstrating efficacy of INB03 as part of combination therapy for
cancer are available.
Our INB03 platform can be
used in cancer patients in many ways. The Phase I trial suggests the drug should not be used alone to treat cancer but used in combination
with, but not limited to, other cancer therapies including cytotoxic chemotherapy, immunotherapy, radiation and surgery. We believe that
INB03 can also be used to treat many types of hematologic and epithelial cancers.
INB03 and 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 be blinded, randomized
clinical trials using validated end-points that have been authorized by a regulatory authority – the FDA, TGA, MHRA, EMA, etc. Currently,
all planned studies will be performed in North America, AUS and/or the UK. Studies will be expanded to Europe and beyond as resources
permit and development needs expand. Because there are no therapies similar to INB03 or XPro approved in any market and no therapies approved
for the treatment of the diseases we are pursuing, 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 “Government Regulation”),
and in the setting of COVID-19, Emergency Use Authorization. We cannot predict which, if any, of these programs we will benefit from without
further discussions with the FDA. Similar programs exist in the EU with the EMA. We will engage the EMA once we have initiated Phase II
trials in the United States and Australia.
12
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 is not an effective treatment strategy, but that 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 AUS 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 will be 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, MRI measures of white matter tract neuroinflammation, axonal
quality and axon myelin, and MRI measures of gray matter quality after XPro therapy. 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 allow the Company to choose a design the Phase II trials described above.
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 hopes to start patient enrollment
in the second half of 2022. We have an active partnering position as it relates to XPro development in neurodegenerative and neuropshyciatric
diseases, although no partnering discussion 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. We may to have biopharma partners participate in this decision making. We
may also seek to be acquired at this stage.
13
INKmune: Our NK cell Directed Product Candidate
INKmune is our lead 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 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 if these two strategies has yet to be worked out, they do not appear
to be identical. In summary, INKmune converts resting NK cells in to tumor killing memory like NK cells. (Figure 1 below).
14
The ability of NK cells to kill tumor cells depends on the strength
and duration of the cell-cell interaction. This is call 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).
15
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 UK
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.
Because INKmune primes NK cells to target naturally
occurring antigens, we believe INKmune can be used in 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