inmb-20251231
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, 2025
☐ 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)
(561)710 0512
(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 $51 million as of the last business day of the registrant’s most recently completed second fiscal quarter (June 30, 2025), 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 30, 2026, there are 26,585,258 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 2026 Annual Meeting of Shareholders to be filed with the Securities and Exchange Commission within 120 days after the fiscal year ended December 31, 2025.
FORM 10-K
FOR THE YEAR ENDED DECEMBER 31, 2025
TABLE OF CONTENTS
Item Number and Caption Page
Forward-Looking Statements ii
PART I 1
1. Business 1
1A. Risk Factors 36
1B. Unresolved Staff Comments 56
1C. Cybersecurity 56
2. Properties 56
3. Legal Proceedings 56
4. Mine Safety Disclosures 56
6. [Reserved] 57
7A. Quantitative and Qualitative Disclosures About Market Risk 66
8. Financial Statements and Supplementary Data 67
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 74
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
Company Overview
INmune
Bio is a clinical-stage biotechnology company dedicated to developing and commercializing a pipeline of product candidates designed to
reprogram the innate immune system. Our mission is to address a broad range of diseases where chronic inflammation and immune dysfunction
are primary drivers of pathology.
Lead
Program: CORDStromTM for RDEB Our primary focus is the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)
using CORDStrom, our proprietary, pooled, human umbilical cord-derived mesenchymal stromal cell platform. RDEB is a devastating pediatric
orphan disease caused by mutations in the COL7A1 gene. This genetic deficiency leads to systemic complications, including highly
debilitating skin blistering, chronic non-healing wounds, dysphagia, and failure to thrive. Over time, the chronic inflammatory environment
associated with RDEB often progresses to fatal squamous cell carcinoma. RDEB is a systemic disease with no approved systemic treatments.
The only approved products to date are topical and do not address the systemic issues of the disease, which is the focus of CORDStrom.
CORDStrom has recently completed a pivotal, blinded, randomized cross-over
trial. Based on these data, the Company is transitioning toward regulatory submission and commercialization. We intend to file a Marketing
Authorization Application (MAA) in the United Kingdom in July 2026 and the European Union (EU) in September 2026, followed by a Biologics
License Application (BLA) with the U.S. Food and Drug Administration (FDA) targeted for December 2026.
Neuroinflammation
and Oncology Pipelines In addition to our lead rare
disease program, the Company is advancing two other clinical-stage platforms:
By
targeting the innate immune system across these distinct therapeutic areas, INmune Bio aims to deliver disease-modifying treatments
for patients with high unmet medical needs.
CORDStrom
CORDStrom,
developed by INmune Bio circa 2020, represents a breakthrough in mesenchymal stromal cell technology. The CORDStrom platform
leverages, among other things, proprietary screening, pooling and expansion techniques to create off-the-shelf, allogeneic, pooled
human umbilical cord - derived mesenchymal stromal cells as medicines to treat complex inflammatory diseases. CORDStrom is
manufactured in the United Kingdom under the direction of Mark Lowdell, the Company’s CSO, using a supply of human umbilical
cords. 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. Initially developed at
the INKmune manufacturing facilities utilizing United Kingdom academic grant funding, CORDStrom is a product platform that shows
promise as a therapy for RDEB and many other debilitating conditions. While the first generation CORDStrom product is agnostic to
indication, the platform enables creation of indication-specific products, which can be tuned for optimization of anti-inflammatory,
immunomodulatory, wound healing, and other characteristics.
1
Children with RDEB have skin that is damaged by even the smallest amount of friction which causes severe blistering, deep wounds, and
scars. It is caused by a fault in a gene that makes collagen, a protein that holds the skin layers together. There are limited options
available for treatment, none that adequately meet the needs of patients, and the condition gets worse over time with many children reliant
on a wheelchair as they move into their teenage years. Many of those with an RDEB diagnosis will also go on to develop aggressive life-threatening
skin cancer in adulthood caused by the accumulated damage to their skin. The Company estimates roughly 2,000 people suffer from RDEB in
the US, United Kingdom and EU representing a large unmet opportunity to potentially provide routine clinical care to these children.
From 2020 until mid-2024, the Company supplied CORDStrom as an investigational medical product to the Great Ormond Street Children’s
Hospital (“GOSH”), London, and Birmingham Children’s Hospital in connection with the MissionEB study, which was primarily
funded by a grant from the National Institute for Health and Care Research (“NIHR”) and Cure EB in the United Kingdom. INmune
Bio was compensated for CORDStrom used in the trial and was not a sponsor of the MissionEB study. The investigators recently concluded
the double blinded, randomized, placebo-controlled arm of the study, which evaluated the safety and efficacy of CORDStrom in 30 pediatric
patients (less than 16 years old) in the United Kingdom with intermediate and severe RDEB using a novel cross-over clinical trial design.
Patients were randomized to CORDStrom or placebo arms and received two intravenous infusions two weeks apart and then followed for 9 months.
Each child then crossed over to the other arm and received two doses of placebo or CORDStrom two weeks apart with a further 9-month follow-up.
All
patients were treated as day-cases and no CORDStrom related serious adverse events were reported through the study. Top-line results
showed the treatment was easily administered, well tolerated and there were beneficial effects across all types of patients receiving
CORDStrom with respect to Itch Man Scale, iscorEB clinician score and iscorEB skin involvement. Most notably, CORDStrom significantly
reduced itch scores as measured by the Itch Man Scale. In patients with the most severe disease activity, CORDStrom reduced itch at 3
months and led to a sustained reduction of over 27% at 6 months. These results demonstrate a clinically meaningful reduction in itch
severity sustained over time. Intermediate group patients showed a broader range of improvements, including reduced skin involvement
and less pain as well as large reduction in itch. The younger patients (less than 10 years old) showed improvements in skin score,
indicating better skin integrity and reduced disease activity. Interviews with patients and caregivers on completing follow up strongly
support the clinical benefits of the therapy; both caregivers and patients were able to correctly identify which treatment had been CORDStrom
and which had been placebo. Those who completed the study are asking to continue on therapy, which the Company intends to pursue as an
open-label study.
2
Further
analysis of the data by the Company noted an improvement in pain of the patients compared to placebo as follows:
In
addition, further analysis of the data by the Company showed an improvement of wellbeing compared to placebo as follows:
The Mission EB data form the basis of a license that was entered into
between INmune Bio and GOSH, whereby the Company gains exclusive access to the clinical study data for commercial uses in exchange for
payment of an initiation milestone of approximately $0.3 million which the Company paid during July 2025 and a single development milestone
of up to 6 million pounds (approximately $8.1 million at December 31, 2025) due on receipt of first marketing authorization from the FDA,
European Medicines Agencies (“EMA”), or the United Kingdom’s Medicines and Healthcare products Regulatory Agency (“MHRA”),
which has not occurred yet.
After
reviewing results of the Mission EB study, the Company initiated a Type C meeting with the FDA to obtain CMC and regulatory feedback and
submitted information, data and requests for Rare Pediatric Disease and Orphan Drug Designations (RPDD/ODD).
The FDA granted RPDD to the Company’s CORDStrom product on December
13, 2024. CORDStrom remains eligible to receive a Priority Review Voucher (PRV) if approved by the FDA on or prior to September 30, 2029,
assuming the PRV program is not extended. If granted, a PRV can be redeemed to receive priority review for a different product. Alternatively,
a PRV may be transferred or sold to another organization.
The
FDA granted ODD to the Company’s CORDStrom product on January 6, 2025. Benefits of ODD include certain tax credits and eligibility
for select grants, waiver of FDA user fees, including the BLA application fees, access to frequent meetings with the FDA for efficient
drug development, and eligibility for seven (7) years of market exclusivity post approval.
3
The
Company plans to prepare for and hold a pre-BLA meeting to discuss particulars of its planned BLA submission, with intent to submit a
BLA this year seeking approval of CORDStrom for treatment of RDEB. Concurrently, the Company will also seek to submit MAAs to the EU and
United Kingdom in 2026.
XPro
We believe our XPro platform can be used as a CNS (“central nervous
system”) therapy to target glial activation to prevent progression of AD along with other inflammatory diseases. The primary focus
of the Company’s development efforts for XPro is AD. In each case, we believe neutralizing soluble Tumor Necrosis Factor (“sTNF”)
is a cornerstone to the treatment of neuroinflammation and immune dysfunction in these diseases.
We believe the dominant negative tumor necrosis factor (“DN-TNF”)
platform can be used to treat selected neurodegenerative diseases by reducing neuroinflammation without immunosuppression. The Company
believes the core pathology of cognitive decline is a combination of neurodegeneration and synaptic dysfunction. Neurodegeneration is
nerve cell death that may include demyelination. Synaptic dysfunction means the connections between nerve cells cease to work efficiently
and may decrease in number. The combination of neurodegeneration and synaptic dysfunction causes cognitive decline and behavioral changes
associated with AD. XPro completed a Phase I trial treating patients with Alzheimer’s disease that was partially funded by a Part-the-Clouds
Award from the Alzheimer’s Association. We believe XPro targets activated microglia and astrocytes of the brain that produce sTNF
that promotes nerve cell loss, synaptic dysfunction and prevents myelin repair - key elements in the development of dementia. In animal
models, elimination of sTNF prevents nerve cell dysfunction, reverses synaptic pruning and promotes myelin repair. The Phase I trial in
patients with biomarkers of inflammation with AD has been completed. The open label, dose escalation trial was designed to demonstrate
that XPro can safely decrease neuroinflammation in patients with AD and biomarkers of inflammation. The goal of the Phase 1 trial was
to demonstrate safety in the target population (patients with AD), demonstrate target engagement by showing XPro got into the brain in
therapeutically relevant concentrations and reduced neuroinflammation) and identify the best dose for phase 2. XPro got into the brain
(Figure 1a) and dose dependently decreased biomarker of neuroinflammation in the CSF (Figure 1b) with patients treated with
the highest dose (1mg/kg/week dose) having the greatest reduction in neuroinflammation. A broad analysis of proteomic changes following
treatment of XPro revealed significant changes in CSF proteins related to CNS neuronal function, immune/inflammatory response, Cytoskeletal,
metabolic processes, and dendritic spine morphogenesis and synaptic plasticity. Of note, XPro reduced neuronal injury markers Visinin-like
protein-1 (91%) and Neurofilament light (84%), improved measures of synaptic function as evinced by a 222% increase in Contactin 2 and
a 56% decrease neurogranin. Finally, XPro significantly reduced CSL levels of p-Tau217 (43%) and pTau181 (2%) after 3 months of therapy
(Figure 1c).
A B C
Figure 1: (A) XPro gets into the brain
at therapeutically relevant concentrations. XPro neutralizes 99.9% of sTNF when drug levels exceed two logs. (B) XPro dose dependently
reduces CSF inflammation in the brain. CSF composite – a composite score of change of all cytokines measured in the OLINK Target
48 Cytokine panel. (C) XPro (at 1 mg/kg dose) reduces CSF pTau217 and pTau181 as measure by proteomics.
4
The Phase II study, also known
as AD-02 and MINDFuL, was a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the safety, tolerability,
and efficacy of XPro in individuals with early Alzheimer’s disease with biomarkers of inflammation. The primary goal of AD02 was
to determine if XPro could affect cognition following 6 months of treatment. Participants with a diagnosis of early AD (mild cognitive
impairment or mild AD) were randomized in a 2:1 (XPro:Placebo) ratio to receive either 1.0 mg/kg of XPro or placebo via weekly subcutaneous
injections for 6 months. An enrichment strategy mirroring to the successful strategy used in the Phase I trial was used to align the mechanism
of the drug with the patients AD pathology. Eligibility required the presence of at least one
inflammatory biomarker—either high-sensitivity C-reactive protein (hsCRP > 1.5 mg/L), erythrocyte sedimentation rate (ESR >
10 mm/h), hemoglobin A1c (HbA1c > 6.0% DCCT), or at least one APOE4 allele. The primary endpoint was the Early and Mild Alzheimer’s
Cognitive Composite (EMACC), with secondary endpoints of Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB), Everyday Cognition
Scale (E-Cog), Neuropsychiatric Inventory (NPI-12), ADCS-ADL, and biomarkers such as pTau-217 and GFAP. MRI-based neuroinflammation and
brain volumetrics are also evaluated. The AD program had sites in Australia, Canada, the United Kingdom, France, Germany, Spain, Czech
Republic and Slovakia.
Full enrollment in the Phase
II AD trial occurred in late 2024 with 208 patients enrolled and top-line data was received during June 2025. In the Phase 2 MINDFuL trial
of XPro in patients with early Alzheimer’s Disease (AD) with biomarkers of inflammation, the modified intent-to-treat (mITT)
population (n=200) did not meet the primary and key secondary endpoints (figure 1). Efficacy, Demographics and Safety data are
shown below.
Figure 1: Phase 2 Study Results – mITT population Primary
and Key Secondary Endpoints, Change From Baseline
Figure 1: As these graphs depict, the primary
and secondary endpoints in this trial were not met as no decline in the placebo groups were observed. A trend was observed in NPI that
favored XPro over placebo. For reference, A higher EMACC score =better, A lower CDR and NPI score is better. EMACC: LS Mean Diff (SE):
-0.018 (0.0414), 90% CI: -0.0860, 0.0509, p-value: 0.672. CDR-SB: LS Mean Diff (SE): -0.11 (0.185), 90% CI: -0.417, 0.195, p-value: 0.5491.
NPI: LS Mean Diff (SE): -0.9 (0.78), 90% CI: -2.18, 0.39, p-value: 0.2499
Prespecified subgroups analyses
suggested a signal that favored XPro in a predetermined population of patients that were both amyloid positive and had a higher burden
of inflammation defined by 2 or more biomarkers of inflammation (from hereon referred to as enriched group). As shown in figure 2, the
mITT placebo group did not decline whereas patients in the enriched group did decline. Decline in the placebo group is required to test
the ability of a treatment to prevent or slow decline.
5
Figure 2: Phase 2 Study Results – Placebo group decline in
the mITT and enriched population
Figure 2: Placebo patients in the mITT
did not show decline on the EMACC over the 24 week study. In the enriched group, placebo patients did decline over 24 weeks.
To evaluate a subgroup after
missing the primary endpoint, we used effect size as the primary metric due to the smaller sample size (n=100). Effect size, measured
by Cohen’s D, is well-suited for small samples and allows comparisons across different measures (e.g., cognitive tests and biomarkers).
Unlike p-values, which indicate the likelihood of results being due to chance, effect size reflects clinical relevance and is commonly
used for signal detection in Phase 2 studies.
We defined a promising signal
as a minimum effect size of 0.2, where XPro outperformed placebo on multiple endpoints aligned with our hypothesis and the drug’s
mechanism of action. Results must also be appropriate for the trial’s parameters, meaning the observed effects should align with
the trial’s duration and endpoints. For example, if a clinical measure typically requires a longer time to show meaningful change
than the trial’s 6-month timeframe, an observed effect on that endpoint would not be considered supportive. Signal detection was
based on the effect size difference in LS mean change from baseline (MMRM model) between XPro and placebo at 6 months, ensuring results
were meaningful, relevant, and appropriate for the trial’s design and objectives.
Using this method, the enriched
population (50% of the total sample, n=100) showed trends toward improvement with XPro on the primary endpoint (EMACC) and a key secondary
endpoint (NPI) (Figure 3a). With the placebo group showing the expected decline on EMACC over six months, a beneficial effect of
XPro became evident. EMACC, which measures cognition (higher scores are better), showed an effect size of 0.27, exceeding the company’s
threshold of 0.2, though the p-value of 0.16 fell short of the <0.1 target. For neuropsychiatric symptoms (NPI), the enriched population
showed a stronger beneficial effect compared to the overall population, with an effect size of -0.23 and a p-value of 0.2. There was no
effect on CDR-SB, which measures cognition and function (lower scores are better). Within the dose compliant group of patients, there
was an increased benefit seen corresponding to the amount of XPro received during the trial (Figure 3b). We also evaluated the effect
size of additional endpoints (Figure 4). Across most endpoints, XPro showed favorable trends, with effect sizes approaching the
0.2 threshold for clinical relevance.
6
Figure 3a: Phase 2 Study Results – Enriched population primary
and key secondary endpoints, change from baseline
Figure 3: The enriched population show
effect size >0.2 favoring XPro on the EMACC and NPI. , A higher EMACC score =better, A lower CDR and NPI score is better. EMACC: LS
Mean Diff (SE): 0.086 (0.0603), 90% CI: -0.0146, 0.1857, p-value: 0.1594. CDR-SB: LS Mean Diff (SE): -0.08 (0.307), 90% CI: -0.593, 0.426,
p-value: 0.7859. NPI: LS Mean Diff (SE): -1.6 (1.25), 90% CI: -3.71, 0.47, p-value: 0.2003
Figure 3b: Phase 2 Study Results – XPro had greater impact
on dose compliant patients
7
Figure 4: Effect size of XPro across multiple endpoints described
as absolute effect sizes (cohen’s D).
Demographics
8
Safety
Safety: Treatment Emergent Adverse Events (TEAEs): Safety Analyses Set
Any TEAE by Maximum Severity
Any Treatment-Related Serious TEAE 0 2 (1.4%) 2 (1.0%)
Any TEAE Leading to Treatment Discontinuation 2 (3.0%) 12 (8.6%) 14 (6.8%)
Any TEAE Leading to Study Withdrawal 2 (3.0%) 12 (8.6%) 14 (6.8%)
Any TEAE with Fatal Outcome 0 0 0
9
The Company believes these findings from the Phase 2 results indicate
that XPro may offer benefits to a readily identified subgroup of Alzheimer’s patients across all ages with biomarker-defined neuroinflammation,
regardless of comorbidities or ApoE4 status and potentially lays the foundation for advancing XPro as a promising treatment for AD. The
Company participated in an end-of-phase 2 meeting with the FDA during January 2026. The minutes from the end-of phase 2 meeting confirmed
regulatory alignment on the Company’s proposed integrated Phase 2b/3 clinical development strategy for XPro in early AD.
The Company intends to pursue
strategic partnership opportunities to support the further development of XPro in neurodegenerative and/or other indications. The Company
does not currently plan to independently advance XPro into later-stage development.
INKmune
We have demonstrated that INKmune improves the ability of the patient’s
own NK cells to attack their tumor. INKmune interacts with the patient’s NK cells to convert them from inert resting NK cells into
memory-like NK cells that kill the patient’s cancer cells. INKmune is designed to be given to patients after their immune system
has recovered after cytotoxic chemotherapy to target the residual disease that remains after treatment with cytotoxic therapy. We believe
INKmune can be used to treat numerous hematologic malignancies and solid tumors including leukemia, multiple myeloma, lymphoma, lung,
ovary, breast, renal and prostate cancer. The Company sponsored a Phase I trial using INKmune to treat patients with high risk MDS/AML,
a form of leukemia in the UK. Due to Covid restrictions only one patient completed treatment and follow-up in the Phase I trial for MDS;
a further three AML patients were treated compassionately. Due to the post-Covid recruitment problems, the Company decided to terminate
further enrollment in the MDS/AML trial in March 2024. Nonetheless, from the four patients treated and completing follow-up it was determined
that INKmune therapy is safe and promotes development of cancer killing memory-like NK cells that are activated and can kill NK-resistant
cancer cells which can be found in the patient’s circulation for up to 4 months after completion of treatment. The Company initiated
a separate multicenter Phase I/II trial of INKmune in a metastatic castrate resistant prostate cancer in the US and enrolled the first patient in December 2023.
The Company’s Phase
I/II trial using INKmune to treat patients with metastatic castrate resistant prostate cancer (mCPRC) is an open label trial. Biomarker
data from the patients will be visible as patients are treated. The Company plans to report data from each cohort as it becomes available.
The trial was completely enrolled during the fourth quarter of 2025 and top-line data is anticipated approximately 6 months thereafter.
Topline data are divided into immunologic and tumor response variables. The most important immunologic response variable is related to
memory-like NK cell persistence. There are 3 important variables to tumor response: i) blood PSA changes; ii) change in PSMA-PET scan
and iii) change in circulating tumor DNA (ctDNA). INKmune is not a hormone-targeting treatment and will not directly reduce PSA levels
but tumor load measured by PSMA-PET and/or ctDNA are expected to decrease with treatment. We do not expect this 6-month trial to provide
survival data.
Due to capital constraints, the Company does not intend to move INKmune further into development at this time.
Intellectual Property
We seek to protect our therapeutic
programs by continuously developing patent properties covering novel compositions, formulations, purpose-limited compositions, combination
treatments, methods of medical treatment, and other inventions, whether created internally or in-licensed, in the United States Patent
& Trademark Office (the “USPTO”), the World Intellectual Property Organization (“WIPO”) under the Patent Cooperation
Treaty (“PCT”), and in patent offices for various foreign jurisdictions. While each invention is unique and territories for
protection are decided on a case-by-case basis, we generally pursue patents in Australia, Canada, Europe, Japan, and the United States,
and sometimes in Brazil, China and/or Korea. We currently have in our portfolio thirteen (13) issued patents and twenty-seven (27) pending
patent applications, including both company-owned and in-licensed properties. The following sections and corresponding tables summarize,
for each of our current therapeutic programs, our pending and granted patent positions, to the extent publicly available, as of the time
of preparing this document:
10
CORDStrom (MSCs)
CORDStrom is a cell suspension
for intravenous infusion or injection comprising aseptic, allogeneic, pooled human umbilical cord derived mesenchymal stromal cells (hucMSCs).
CORDStrom solves certain manufacturing and CMC limitations known to affect mesenchymal stem/stromal cell products, namely, improved batch-to-batch
consistency and scalable manufacturing. The following table summarizes current IP covering our CORDStrom platform technology:
CORDStrom compositions and formulations 2 0 global 2045
Use of CORDStrom for treating disease 1 0 global 2045
DN-TNF Platform Technology
The DN-TNF Platform Technology covers a variety of dominant negative
tumor necrosis factor variant proteins, including the pegylated DN-TNF protein variants known as XPro and INB03. The following table summarizes
current IP covering our DN-TNF platform technology:
DNTNF compositions and formulations 2 0 global 2044-2045
DNTNF manufacturing/CMC 1 0 global 2045
INB-16 / INKmune (Oncology)
INKmune is a replication-incompetent
derivative of our proprietary INB-16 cell line. One commercial application of INKmune includes use as a therapeutic composition designed
to enhance the ability of a patient’s own NK cells to seek, recognize and eliminate cancer. Another commercial application of INKmune
includes use as a cytokine-like agent for enhancing NK cell killing specificity, potency, and efficacy of NK cell -based therapeutics.
The following table summarizes current IP covering INB-16 / INKmune:
INB-16 / INKmune compositions 4 0 global 2043
Use of INKmune for treating disease 3 5 global 2036-2043
11
General IP Disclosures
Our commercial success
depends in part on obtaining and maintaining patent and trade secret protections, where applicable, of our current and future product
candidates and the methods used to manufacture them, as well as successfully defending our patents against third-party challenges.
Our ability to stop third
parties from making, using, selling, offering to sell or importing our products depends on the extent to which we have rights under valid
and enforceable patents or trade secrets that cover these activities, and whether we are able to enforce such rights. We cannot assure
you that our pending patent applications will result in issued patents, or that any or all rights will be enforceable in every jurisdiction
whether or not patent rights are sought.
International PCT patent applications
cover all 152 nations which are signatories of the PCT. However, our global IP strategy generally targets Australia, Canada, Europe, Japan,
and the United States, and sometimes Brazil, China and/or Korea, as targets for extending patent protection under the PCT. Decisions regarding
which countries to extend patent coverage under the PCT is taken on a case-by-case basis, subject to normal business considerations such
as value and return on investment. Given the markets for products we are developing, we consider the foregoing jurisdictions to amount
to “global” coverage as used herein as it relates to IP.
The above disclosures related
to patents and patent applications are subject to change based on strategic patent portfolio building decisions, which may include refiling
and reissue, certain abandonments, including those in favor of continuing patent applications, maturations from provisional to non-provisional
filings, and other regular patent prosecution activities.
Trademarks
The designations INMUNE BIOTM,
CORDStromTM, INB16TM, INKmuneTM, XPro1595TM and XProTM are trademarks of INmune
Bio Inc. Some or all these trademarks may be protected by registrations or applications pending at the USPTO and other trademark registration
authorities globally. As part of the trademark registration process, we may be required to submit a statement of use evidencing bona
fide use of each mark in commerce. By nature of being in the biopharmaceutical business, certain regulatory requirements must be met
in connection with certain products and/or services prior to receiving marketing authorization from a regulatory agency, and thus it may
take some time before products and/or services are offered for sale and a statement of use can be submitted for perfecting trademark registration.
For these reasons, we may be required to obtain extensions of time, or to refile applications, seeking registration of trademarks. We
cannot guarantee that a given trademark application will be allowed or issued in a respective office for each jurisdiction.
IP License Agreements
Immune Ventures, LLC License Agreement
On October 29, 2015, the Company
entered into an exclusive license agreement (the “INKmune License Agreement”) with Immune Ventures, LLC (“Immune Ventures”).
Pursuant to the INKmune License Agreement, we were granted an exclusive worldwide, sub-licensable, royalty-bearing license to commercialize
INKmune (the “INKmune License”). In consideration for the INKmune License, we are obligated to pay Immune Ventures certain
milestone and royalty payments.
The term of the Immune Ventures
Agreement began on October 29, 2015, and, if not terminated sooner pursuant to the agreement, ends on a country-by-country basis on the
date of the expiration of the last to expire patent rights where patent rights exist. Subject to granting, prosecution-related patent
term adjustments, and requirements for maintenance and renewals, the latest to expire patent is scheduled to expire on March 15, 2038
(“Natural Expiration”). Upon Natural Expiration of the Immune Ventures Agreement, we shall have a fully paid up, perpetual,
royalty-free license without further obligation to Immune Ventures. The Immune Ventures Agreement can be terminated by Immune Ventures
if, after 60 days from our receipt of notice that we have not made a payment under the Immune Ventures Agreement we still do not make
this payment. On July 20, 2018 and October 30, 2020, the parties amended the agreement under which the Company was required to achieve
milestones pursuant to the agreement.
On April 17, 2023, the parties
executed an additional amendment to the agreement under which the Company removed the due diligence requirements to achieve reasonable
commercial efforts to bring INKmune to market. This removed all requirements of clinical trial timelines and the filing timelines of an
NDA or equivalent. All other provisions in the INKmune License Agreement shall continue in full force and effect.
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University of Pittsburg License Agreement
On October 3, 2017, the Company
entered into an Assignment and Assumption Agreement with Immune Ventures related to intellectual property licensed from the University
of Pittsburgh. Pursuant to the Assignment and Assumption Agreement (the “Assignment Agreement”), Immune Ventures assigned
all its rights, obligations and liabilities under an Exclusive License Agreement between the University of Pittsburgh – Of the Commonwealth
System of Higher Education (“Licensor”) and Immune Ventures to INmune Bio (“Licensee”), (the “PITT Agreement”).
As consideration under the
PITT Agreement, we are obligated to pay: (i) annual maintenance fees, (ii) royalty payments based on the sale of products making use of
the licensed technology, and (iii) milestone payments.
The PITT Agreement expires
upon the earlier of: (i) expiration of the last claim of the Patent Rights forming the subject matter of the PITT Agreement; or (ii) the
date that is 20 years from the effective date of the agreement (June 26, 2037).
The Company may terminate
the PITT Agreement upon 3 months prior written notice provided all payments under the license are current. Licensor may terminate the
PITT Agreement upon written notice if: (i) the Company defaults as to performance of material obligations which have not been cured within
60 days after receiving written notice; or (ii) the Company ceases to carry out its business, becomes bankrupt or insolvent, applies for
or consents to the appointment of a trustee, receiver or liquidator of its assets or seeks relief under any law for the aid of debtors.
Xencor License Agreement
On October 3, 2017, the Company
entered into a license agreement with Xencor, Inc. (“Xencor”), which has discovered and developed a proprietary biological
molecule that inhibits soluble tumor necrosis factor (the “Xencor Agreement”). During June 2021, the Company entered into
the First Amendment to License Agreement with Xencor. Pursuant to the Xencor Agreement, Xencor granted the Company an exclusive worldwide,
royalty-bearing license in licensed patent rights, licensed know-how and licensed materials (as defined in the Xencor Agreement) to make,
develop, use, sell and import any pharmaceutical product that comprises, contains, or incorporates Xencor’s proprietary protein
known as “XPro” that inhibits soluble tumor necrosis factor (or all modifications, formulations and variants of the licensed
protein that specifically bind soluble tumor necrosis factor) alone or in combination with one or more active ingredients, in any dosage
or formulation. The Xencor Agreement expires upon the later of: (a) the expiration of the last to expire valid claim covering any pharmaceutical
product that contains, comprises, or incorporates Xencor’s proprietary protein known as XPro alone or in combination with one or
more active ingredients, in any dosage or formulation. (“Licensed Product”) in such country or (b) ten years following the
first sale to a third party of the licensed product in such country. Net Sales with respect to any Licensed Product is the gross amounts
invoiced by us for sales of the Licensed Products less deductions actually incurred. A valid claim is an issued, unexpired or pending
claim with the patent rights that Xencor controls as of October 3, 2017 which patent rights are necessary to make, develop, use, sell,
have sold, offer for sale and import a Licensed Product in the Field (the Field means all applications for the treatment of diseases in
humans) or the Product Patent Rights, which claim has not lapsed, been abandoned, been revoked or been held to be unpatentable, invalid
or unenforceable by a final judgment of a court or other governmental agency or competent jurisdiction from which no appeal can be or
is taken within the time allowed for appeal and which has not been admitted to be invalid or unenforceable through reissue, re-examination,
disclaimer or otherwise. Product Patent Rights shall mean any and all our patent rights that are necessary to make, develop, use, sell,
have sold, offer for sale and import a Licensed Product in the Field, including any improvements or patent rights directed to the Licensed
Product. Either party may terminate the Xencor Agreement upon 60 days’ (10 days for any payment default) prior written notice to
the other party after the breach of any material provision of the agreement by the other party if the breaching party has not cured the
breach within the 60-day period (10-day period for any payment default) following written notice of termination by the non-breaching party.
We can terminate the Xencor Agreement upon 180 days prior written notice to Xencor. Xencor may terminate the Xencor Agreement in its entirety
or with respect to any specific Licensed Product upon written notice in the event that we contest, oppose or challenge or assist any party
in contesting, opposing or challenging, Xencor’s ownership of, or the enforceability or validity of the Patent Rights that Xencor
controls as of October 3, 2017 which Patent Rights are necessary to make develop, use, sell, have sold, offered for sale and import a
Licensed Product in the Field. Either party may terminate the Xencor Agreement upon written notice to the other party upon or after the
insolvency, bankruptcy, dissolution or winding up of such other party or the making or seeking to make or arrange an assignment for the
benefit of creditors of such other party or the initiation of proceedings in voluntary or involuntary bankruptcy which proceeding, or
action remains undismissed or unstayed for a period of more than 60 days.
In consideration of the Xencor
Agreement, we agreed to royalty payments and a percentage of any payments received in exchange for a sub-license.
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CORDStrom License Agreement – Clinical
Trial Data
On February 6, 2025, the
Company and Great Ormond Street Hospital NHS Foundation Trust (“GOSH”) executed an exclusive commercial use license to clinical
trial data associated with the MissionEB trial (ISRCTN14409785). The Company owns the intellectual property covering the CORDStrom product,
the investigational medicinal product (“IMP”) used in the MissionEB trial. In addition, the Company owns IP and maintains
trade secret protections covering the manufacturing of CORDStrom. With this license to the clinical trial data, the Company intends to
prepare applications seeking marketing authorization of CORDStrom for treatment of pediatric recessive dystrophic epidermolysis bullosa
(“RDEB”) in each of the FDA, EMA, and MHRA. Terms of the GOSH license include an upfront payment of £250,000 (approximately
$0.3 million) which the Company paid during 2025 and a single milestone payment of up to £6,000,000 (approximately $8.1 million
at December 31, 2025) due on the first to occur marketing authorization to be granted by the FDA, EMA or MHRA. Under the license agreement,
the Company was previously obligated to provide CORDStrom for use in the MissionEB clinical study at no cost. During February 2026, the
MissionEB study was formally closed, and the Company’s obligation to supply CORDStrom in connection with that study has terminated
in accordance with the terms of the license agreement. As a result, the Company has no remaining contractual product supply obligations
related to the MissionEB study under the license agreement. The Company intends to provide CORDStrom at no cost for use in a contemplated
follow-on clinical study referred to as “MissionEB II” however, no definitive agreement governing such study has been executed,
and the Company has no present contractual obligation to supply product for MissionEB II.
Government Regulation
The
FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among
other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging,
storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting
of biologics such as those we are developing. We, along with third-party contractors, will be required to navigate the various preclinical,
clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies
or seek approval or licensure of our product candidates. Generally, before a new therapeutic product can be marketed, considerable data
demonstrating a biological product candidate’s quality, safety, purity and potency, or a small molecule drug candidate’s quality,
safety and efficacy, must be obtained, organized into a format specific for each regulatory authority, submitted for review and approved
by the regulatory authority. For biological product candidates, potency is similar to efficacy and is interpreted to mean the specific
ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through
the administration of the product in the manner intended to effect a given result.
Failure
to comply with the applicable U.S. requirements at any time during the product development process, approval process or post-marketing
may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s
refusal to approve pending applications from the sponsor, withdrawal of an approval, a clinical hold, untitled or warning letters, product
recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals
of government contracts, restitution, disgorgement and civil or criminal penalties. Any agency or judicial enforcement action could have
a material adverse effect on our company and our products or product candidates.
U.S. Biologics Regulation
In
the United States, biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act (the “FDCA”),
the Public Health Service Act (“PHSA”), and other federal, state, local, and foreign statutes and regulations. The process
of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, and local statutes and regulations requires
the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during
the product development process, approval process or following approval may subject an applicant to administrative action and judicial
sanctions. The process required by the FDA before biologic product candidates may be marketed in the United States generally involves
the following:
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● satisfactory completion of an FDA Advisory Committee review, if applicable;
Preclinical
and Clinical Development
Prior
to beginning any clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for
authorization from the FDA to administer an investigational new drug product to humans. The central focus of an IND submission is on the
general investigational plan and the protocol or protocols for preclinical studies and clinical trials. The IND also includes results
of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product,
chemistry, manufacturing and controls information, and any available human data or literature to support the use of the investigational
product. In April 2025, the FDA published a roadmap to reduce animal testing in preclinical safety studies, including those required in
INDs, with scientifically validated new approach methodologies. An IND must become effective before human clinical trials may begin. The
IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day period, raises safety concerns
or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA
must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not
result in FDA authorization to begin a clinical trial.
In
addition to the IND submission process, supervision of human gene transfer trials includes evaluation and assessment by an institutional
biosafety committee (“IBC”), a local institutional committee that reviews and oversees research utilizing recombinant or synthetic
nucleic acid molecules at that institution. The IBC assesses the safety of the research and identifies any potential risk to public health
or the environment and such review may result in some delay before initiation of a clinical trial.
Clinical
trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in
accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation
in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters
to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made
for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, an independent
IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent
form before the clinical trial begins at that site, and must monitor the study until completed. Regulatory authorities, the IRB or the
sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable
health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of
qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether
or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial
if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. There
are also requirements governing the reporting of ongoing preclinical studies and clinical trials and clinical study results to public
registries.
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For
purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.
In
some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more
information about the product. These so-called Phase 4 studies may be made a condition to approval of the BLA. Concurrent with clinical
trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the
product candidate, and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things,
must develop methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity
and potency. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that
the product candidate does not undergo unacceptable deterioration over its shelf life.
A
sponsor may choose, but is not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted
under an IND, all IND requirements must be met unless waived. When the foreign clinical study is not conducted under an IND, the sponsor
must ensure that the study complies with certain FDA regulatory requirements in order to use the study as support for an IND or application
for marketing approval or licensure, including that the study was conducted in accordance with GCP, including review and approval by an
independent ethics committee and use of proper procedures for obtaining informed consent from subjects, and the FDA is able to validate
the data from the study through an onsite inspection if the FDA deems such inspection necessary. The GCP requirements encompass both ethical
and data integrity standards for clinical studies.
BLA
Submission and Review
Assuming
successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development,
nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or
more indications. The BLA must include all relevant data available from pertinent preclinical studies and clinical trials, including negative
or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing,
controls, and proposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety
and effectiveness of the product, or from a number of alternative sources, including studies initiated and sponsored by investigators.
The submission of a BLA requires payment of a substantial application user fee to the FDA, unless a waiver or exemption applies.
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In
addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA must contain data to assess the safety
and effectiveness of the biological product candidate for the claimed indications in all relevant pediatric subpopulations and to support
dosing and administration for each pediatric subpopulation for which the product is safe and effective. The Food and Drug Administration
Safety and Innovation Act requires that a sponsor who is planning to submit a marketing application for a biological product that includes
a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial pediatric
study plan within sixty days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. Unless otherwise required
by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted, except that
the PREA will apply to an original BLA for a new active ingredient that is orphan-designated if the biologic is a molecularly targeted
cancer product intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially
relevant to the growth or progression of a pediatric cancer.
Within
60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the
agency accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not
properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with
the additional information. Once a BLA has been accepted for filing, the FDA’s goal is to review standard applications within ten
months after the filing date, or, if the application qualifies for priority review, six months after the FDA accepts the application for
filing. In both standard and priority reviews, the review process may also be extended by FDA requests for additional information or clarification.
The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent and the facility in which it is manufactured,
processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency. The FDA may convene
an advisory committee to provide clinical insight on application review questions. The FDA is not bound by the recommendations of an advisory
committee, but it considers such recommendations carefully when making decisions.
Before
approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve
an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate
to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically
inspect one or more clinical sites to assure compliance with GCPs. If the FDA determines that the application, manufacturing process or
manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing